A Phase 1 interventional study of Placebo and GSK3358699 in Arthritis, Rheumatoid, sponsored by GlaxoSmithKline. Terminated at 1 site in United Kingdom. Open to male participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-12-02.
Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment
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Among 44 studies in Arthritis, Rheumatoid by GlaxoSmithKline — 1 open to participants now, 1 under way, none of them phase 3. Arthritis, Rheumatoid · GlaxoSmithKline.
Among the 44 studies in Arthritis, Rheumatoid by GlaxoSmithKline, this one is the 22nd largest by enrollment of the 40 interventional ones that give a count, is the only one that started in 2018, is one of 13 in phase 1, and was the 38th registered.
3,334 studies on the registry are indexed under Arthritis, Rheumatoid; 444 are open to participants now.
Browse Arthritis, Rheumatoid studies →1 of the 44 studies in Arthritis, Rheumatoid by GlaxoSmithKline is open now, in 9 countries. Recruiting first, the newest first:
GlaxoSmithKline · Sites in Argentina, Brazil, France and 6 more countries
Ages 18–70
By country, each count listing its studies:
Of the 293 Arthritis, Rheumatoid studies recruiting now, 150 (51%) set no upper age limit and 109 (37%) stop at 75 or younger; 15 take children under 18; 36 take healthy volunteers.
This study: 18 Years to 65 Years · male · healthy volunteers too.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
44 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 14 · Phase 2 19 · Phase 3 8
First in 2001; this study’s year is marked. 1 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 48 is below the median of 95 across 2,221 interventional studies indexed under Arthritis, Rheumatoid.
Median enrollment 52 across the 40 interventional studies, 32 across the 3 observational. Of the 40 that completed or were terminated, 17 (43%) have results posted.
This tab as a report to print or save as PDF → With an account.
GlaxoSmithKline is the lead sponsor of 3,650 studies on the registry; 117 are open to participants now.
Of its 265 completed or terminated interventional studies of FDA-regulated products, 241 (91%) have results posted.
None of the studies under way reaches primary completion within a year.
Among the 44 studies in Arthritis, Rheumatoid by GlaxoSmithKline, from their registry updates:
Nothing recorded among them since 2026-09-25.
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This FTIH study, intends to identify the doses of GSK3358699, which are well tolerated by the subjects whilst delivering a robust pharmacodynamic (PD) response. This study will evaluate the safety, tolerability, pharmacokinetic (PK) and PD profile of single (in both fed and fasted states) and multiple ascending doses of GSK3358699 in healthy male subjects within a pre-defined and controlled pharmacodynamic and pharmacokinetic range for each cohort. It also intends to understand the effect of GSK3358699 on systemic markers of inflammation following low dose in vivo lipopolysaccharide (LPS) or Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) challenge and local inflammation in cantharidin-induced blisters. The study has been carefully designed to explore the in vivo biology of the target and the potential for the study drug to become a transformative medicine for subjects in multiple immuno-inflammatory disease indications.
Subjects who are enrolled in the dose escalation treatment Periods of Part A may choose to only take part in the dose escalation treatment Periods 1-3, or may choose to also take part in the challenge Treatment Period (Period 4). If a subject chooses to participate in the dose escalation treatment Periods 1-3 only, or does not (at screening) meet the eligibility criteria specific to challenges (treatment Period 4), a new subject will be recruited for treatment Period 4 only and will be regarded as a replacement subject. The study will be conducted in three Parts. Total duration for participation will be approximately 19 weeks for subjects taking part in all three dose escalation treatment Periods and 23 weeks if a subject takes part in all four treatment Periods of Part A. For replacement subjects only taking part in the challenge treatment Period (Period 4), approximate study duration will be 10 weeks. Total duration for participation will be approximately 9 weeks for Part B and 12 weeks for Part C. The study will be conducted in up to 80 subjects.
Inclusion Criteria: - Subjects enrolled into the study, where they will be administered LPS or GM-CSF challenge, must be 18 to 55 years of age inclusive, at the time of signing the . Subjects enrolled into the study where they will not be administered LPS or GM-CSF challenge must be 18 to 65 years of age inclusive, at the time of signing the informed consent. - Subjects must be overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. - Body weight must be > = 50 kilogram (kg) and (BMI) within the range 18.5-35.0 kg per square meter (kg/m\^2) (inclusive). - Male subjects agreeing to use methods during the treatment Period and for at least 91 days, after the last dose of study treatment and refrain from donating sperm during this Period. - Capable of giving informed consent. Exclusion Criteria: - Current or chronic history of pancreatitis, diabetes mellitus or impaired glucose tolerance, gastrointestinal disease, liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), anaphylaxis, and /or anaphylactoid (resembling anaphylaxis) reactions [Sampson et al 2006], cardiac disease including ventricular arrhythmias or long syndrome, renal disease where clinically significant (minor abnormalities may be permitted base on discussion between investigator and medical monitor), respiratory disease or conditions including but not limited to asthma, (COPD), and bronchiectasis and any current respiratory infection (childhood asthma is not an exclusion criterion), sensitivity or severe allergic responses to any of the challenge agents or cantharidin, or components thereof or a history of drug or other allergy that, in the opinion of the Investigator or GlaxoSmithKline (GSK) Medical Monitor, contraindicates their participation; frequent vasovagal syncope, surgery requiring general anaesthetic or significant trauma in 3 months leading to study enrolment, relevant skin conditions (e.g. recent history of eczema or recurrent eczema, keloid, skin allergies, psoriasis, atopic dermatitis, and vitiligo) which in the opinion of the investigator could pose safety issues or cause interference with study procedures, sepsis, coagulation disorders, peripheral edema, lymphangitis, lymphedema, pleural or pericardial effusion, hemorrhage (eg sub-arachnoid) or hemophilia or a related bleeding disorder. - History of e.g. recurrent basal cell carcinoma, hematological malignancy. - For subjects receiving cantharidin: Presence on either forearm of tattoos, naevi, hypertrophic scars, keloids, hyper- or hypo- pigmentation that may, in the opinion of the Investigator, interfere with study assessments. Subjects with very fair skin, very dark skin, excessive hair or any skin abnormalities that may, in the opinion of the Investigator, interfere with study assessments. - Family history of premature cardiovascular disease or long QT syndrome. - QT interval with Fridericia's correction (QTcF) > 450 millisecond (msec), based on averaged QTcF values of triplicate ECGs obtained over a brief recording period. - Unable or unwilling to refrain from taking prescription or non-prescription drugs (including vitamins and dietary or herbal supplements) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the start of study treatment until completion of the follow-up visit. Paracetamol, at a dose of \<= 2 grams per day was permitted for use anytime during the study. Other concomitant medications will be considered on case by case basis. - The subjects have participated in a clinical trial and received an product within the following time period prior to the first dosing day in the study: 30 days; 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer) or currently in a study of an investigational device. - Exposure to more than four new chemical entities within 12 months prior to the first dosing day. - Previous exposure to intravenous lipopolysaccharide (LPS) in a clinical research setting. - (ALT) >1.5x (ULN) at screening. - >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) at screening. - Presence of surface antigen (HBsAg), positive antibody test result at screening or within 3 months prior to first dose of study treatment. - A positive pre-study drug/alcohol screen at screening. - A positive test for (HIV) antibody at screening. - Persistent clinically significant abnormal C-reactive protein (CRP) levels at screening - Persistent clinically significant abnormal white cell count (WCC) levels at screening (if clinically significant abnormality is detected, WCC can be retested as clinically indicated) - \< 150 x 10\^9 per liter (L) at screening. - Fasted Triglycerides >3.4 millimole per liter (mmol/L) at screening. - Fasted Total cholesterol >7.7 mmol/L at screening. - Random glucose > = 11.1 mmol/L at screening. - Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening. - History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 milliliter [mL]) of beer, 1 glass (125 mL) of wine or 1 (25 mL). - Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period. - Unable to comply with precautions to minimize phototoxicity risk.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
COPD
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Part A will comprise of 4 TPs. The subjects in this cohort will receive GSK3358699, as single escalation dose, during TP (1 to 3) with planned escalated doses as 1 mg, 10 mg and 35 mg. Dose of 1 mg will be given as solution and doses of 10 mg and 35 mg, will be given as a capsule. Each TP will be of 1 day and separated by a washout Period of 14-days. Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10. The subjects in cohort 1 will receive GSK3358699 at a dose level already given in TP 1-3, and will then receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram post administration of GSK3358699. The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge. LPS dose will be based on data of study 207654 (NCT03306589).
Drug: GSK3358699 · Biological: LPS · Other: Cantharidin
Part A will comprise of 4 TPs. The subjects in this cohort will receive GSK3358699, as single escalation dose during TP (1 to 3) with planned escalated doses as 3 mg, 20 mg and 45 mg. Dose of 3 mg will be given as solution and that of 20 and 45 mg, as capsule. Each TP will be of 1 day and separated by a washout Period of 14-days. Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10. The subjects in cohort 2 will receive GSK3358699 at a dose level already given in TP 1-3, and will then receive 60 microgram per meter\^2 of in vivo GM CSF challenge as an intravenous infusion during TP 4, post administration of GSK3358699. The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge GM-CSF infusion. GM-CSF dose will be based on data of study 207654 (NCT03306589).
Drug: GSK3358699 · Biological: GM-CSF · Other: Cantharidin
Part A will comprise of 4 TPs. The subjects in this cohort will receive matching Placebo solution to the study drug GSK3358699 solution for 1 mg and a matching placebo capsule to the study drug GSK3358699, 10 mg and 35 mg capsule, during TP (1 to 3). Each TP will be of 1 day and separated by a washout Period of 14-days. Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10. The subjects in cohort 1 will receive Placebo at a dose level already given in TP 1-3, and will then receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram post administration of Placebo. The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge. LPS dose will be based on data of study 207654 (NCT03306589).
Drug: Placebo · Biological: LPS · Other: Cantharidin
Part A will comprise of 4 TPs. The subjects in this cohort will receive matching Placebo solution to the study drug GSK3358699 solution for 3 mg and a matching placebo capsule to the study drug GSK3358699, for 20 and 45 mg capsule, during TP (1 to 3). Each TP will be of 1 day and separated by a washout Period of 14-days. Post completion of the dose-escalation TPs, an additional dosing TP 4 will be included where the subjects from each TP (1 to 3), will receive control blisters induced on forearm (0.2 % cantharidin) at Day -10. The subjects in cohort 2 will receive Placebo at a dose level already given in TP 1-3, and will then receive 60 microgram per meter\^2 of in vivo GM CSF challenge as an intravenous infusion during TP 4, post administration of Placebo. The subjects will then have blisters induced on the forearm approximately 20 minutes after the challenge GM-CSF infusion. GM-CSF dose will be based on data of study 207654 (NCT03306589).
Drug: Placebo · Biological: GM-CSF · Other: Cantharidin
The subjects in this arm will receive single oral dose of GSK3358699, at a dose level evaluated in Part A, under fasted condition in TP1 followed by fed condition in TP2. This cohort intended to evaluate the effect of food.
Drug: GSK3358699
The subjects in this arm will receive single oral dose of GSK3358699, at a dose level evaluated in Part A, under fed condition in TP1 followed by fasted condition in TP2. This cohort intended to evaluate the effect of food.
Drug: GSK3358699
The dose level for the first cohort in Part C will be decided following completion of Part A of the study for GSK3358699. The subjects in this arm will constitute 3 cohorts each (cohort 4 to 6), where the subjects will receive GSK3358699, as one repeat dose treatment once daily for 14-consecutive days. Subjects will have control blisters induced on the forearm (0.2% cantharidin) on Day -10. On the Day 14 of each cohort, each subject will receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram or an intravenous infusion of GM-CSF, in vivo as 60 microgram per meter\^2. The administration of LPS or GM CSF will be followed by blister induction on forearm (0.2 % cantharidin).
Drug: GSK3358699 · Biological: GM-CSF · Biological: LPS · Other: Cantharidin
The subjects in this cohort will receive a matching placebo to GSK3358699, Part C, as a single oral dose once daily for 14 consecutive days. The subjects in this arm will constitute 3 cohorts each (cohort 4 to 6), where the subjects will receive placebo, as one repeat dose treatment once daily for 14-consecutive days. Subjects will have control blisters induced on the forearm (0.2% cantharidin) on Day -10. On the Day 14 of each cohort, each subject will receive an intravenous in vivo LPS challenge at a dose not exceeding 0.75 nanogram per kilogram or an intravenous infusion of GM-CSF, in vivo as 60 microgram per meter\^2. The administration of LPS or GM CSF will be followed by blister induction on forearm (0.2 % cantharidin).
Drug: Placebo · Biological: GM-CSF · Biological: LPS · Other: Cantharidin
Placebo will be administered as a matching oral solution or matching capsule to study drug GSK3358699, during Part A and C once daily
GSK3358699, will be administered from 1 mg to 45 mg as an oral solution (1 to 10 mg) or as a capsule (3 to 45 mg), in Part A, B and Part C once daily.
The GM-CSF will be administered as an intravenous infusion to subjects as 60 microgram per meter\^2 in Part A (Day 1) and Part C (Day 14).This will be administered for 2 hours approximately, no later than 24 hours post -dose of the GSK3358699 or placebo in Part C
LPS will be administered as an intravenous injection to subjects not exceeding 0.75 nanogram per kilogram in Part A (Day 1) and Part C (Day 14). This will be administered no later than 24 hours post -dose of the GSK3358699 or placebo in Part C.
This will be applied as a topical application with 0.7% cantharidin liquid which will be diluted with acetone to 0.2%.
Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed before. Safety Population consisted of all randomized participants who took at least 1 dose of study treatment.
Time frame: Up to Day 193
Part B: Number of Participants With AEs and SAEs
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed before.
Time frame: Up to Day 30
Part C: Number of Participants With AEs and SAEs
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed before.
Time frame: Up to Day 49
Part A: Number of Participants With Worst Case Chemistry Results by Potential Clinical Importance (PCI) Criteria Post-Baseline Relative to Baseline
Blood samples were collected for analysis of clinical chemistry parameters. PCI ranges were \<30 grams per liter (g/L) (albumin), \<2 or \>2.75 millimoles/L (mmol/L) (calcium), \>1.3\* upper limit of normal (ULN) mmol/L (creatinine), \<3 or \>9 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), and \<130 or \>150 mmol/L (sodium). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change (NC) category. Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100%.
Time frame: Up to Day 193
Part A: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Clinical chemistry parameters assessed were alanine aminotransferase(ALT)(\<10 or \>50 international units per liter\[IU/L\]),alkaline phosphatase(ALP)(\<40 or \>129 IU/L),aspartate aminotransferase(AST)(\<0 or \>37 IU/L),cholesterol(\<2.3 or \>4.9 mmol/L),direct bilirubin(DB)(\<0 or \>5 micromoles\[mcmol\]/L),high density lipoprotein (DL)(\<0.9 or \>1.5 mmol/L),C-reactive protein(CRP)(\<0.0 or \>5.0mg/liter),low DL(\<0 or \>3.0 mmol/L), total bilirubin (\<0 or \>20 mcmol/L),total protein(\<63 or \>83 grams/L),triglycerides(\<0 or \>2.3 mmol/L) and blood urea nitrogen(BUN)(\<4.76 or \>23.24 mg/deciliter).Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category.Participants whose laboratory value category was unchanged(e.g.,High to High) or whose value became normal, are recorded in "To Normal or NC" category.Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Time frame: Up to Day 193
Part B: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze the chemistry parameters.
Time frame: Up to Day 30
Part B: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze the chemistry parameters.
Time frame: Up to Day 30
Part C: Number of Participants With Worst Case Chemistry Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected for analysis of chemistry parameters. PCI ranges were \<30 g/L (albumin), \<2 or \>2.75 mmol/L (calcium), \>1.3\* ULN mmol/L (creatinine), \<3 or \>9 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), and \<130 or \>150 mmol/L (sodium). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100%.
Time frame: Up to Day 28
Part C: Number of Participants With Worst Case Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
Clinical chemistry parameters assessed were ALT (\<10 or \>50 IU/L), ALP (\<40 or \>129 IU/L), AST (\<0 or \>37 IU/L), cholesterol (\<2.3 or \>4.9 mmol/L), DB (\<0 or \>5 mcmol/L), high DL (\<0.9 or \>1.5 mmol/L), CRP (\<0.0 or \>5.0 mg/liter), low DL (\<0 or \>3.0 mmol/L), total bilirubin (\<0 or \>20 mcmol/L), total protein (\<63 or \>83 grams/L), triglycerides (\<0 or \>2.3 mmol/L) and BUN (\<4.76 or \>23.24 mg/deciliter). Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became normal, are recorded in "To Normal or NC" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Time frame: Up to Day 28
Part A: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples collected for analysis of hematology parameters. PCI ranges were \>0.54 proportion of red blood cells in blood (hematocrit), \>180 grams/liter (hemoglobin), \<0.8 \*10\^9 cells/L (lymphocyte count), \<1.5 \*10\^9 cells/L (total absolute neutrophil count \[ANC\]), \<100 or \>550 \*10\^9 cells/L (platelet count), and \<3 or \>20\*10\^9 cells/L (white blood cell \[WBC\] count). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant had values that changed To Low and To High, so the percentages may not add to 100%.
Time frame: Up to Day 193
Part A: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Hematology parameters assessed were activated partial thromboplastin time (APTT) (\<25 or \>37 seconds), basophil count (\<0.0 or \>0.1\*10\^9 cells/L), eosinophil count (\<0.0 or \>0.4\*10\^9 cells/L), fibrinogen (\<1.5 or \>4.0 g/L), mean corpuscle hemoglobin (MCH) (\<26.0 or \>33.5 picogram), mean corpuscle volume (MCV) (\<80 or \>99 femtoliter), monocyte count (\<0.2 or \>1.0\*10\^9 cells/L), prothrombin time (PT) (\<10 or \>12 seconds), red blood cell (RBC) count (\<4.4 or \>5.8\*10\^12 cells/L) and reticulocyte count (\<0.38 or \>2.64 percentage of reticulocytes). Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became normal, are recorded in "To Normal or NC" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Time frame: Up to Day 193
Part B: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze hematology parameters.
Time frame: Up to Day 30
Part B: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Blood samples were planned to be collected to analyze hematology parameters.
Time frame: Up to Day 30
Part C: Number of Participants With Worst Case Hematology Results by PCI Criteria Post-Baseline Relative to Baseline
Blood samples were collected for analysis of hematology parameters. PCI ranges were \>0.54 proportion of red blood cells in blood (hematocrit), \>180 grams/liter (hemoglobin), \<0.8\*10\^9 cells/L (lymphocyte count), \<1.5\*10\^9 cells/L (total ANC), \<100 or \>550\*10\^9 cells/L (platelet count), and \<3 or \>20\*10\^9 cells/L (WBC count). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant had values that changed To Low and To High, so the percentages may not add to 100%.
Time frame: Up to Day 28
Part C: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
Hematology parameters assessed were APTT (\<25 or \>37 seconds), basophil count (\<0.0 or \>0.1\*10\^9 cells/L), eosinophil count (\<0.0 or \>0.4\*10\^9 cells/L), fibrinogen (\<1.5 or \>4.0 g/L), MCH (\<26.0 or \>33.5 picogram), MCV (\<80 or \>99 femtoliter), monocyte count (\<0.2 or \>1.0\*10\^9 cells/L), PT (\<10 or \>12 seconds), RBC count (\<4.4 or \>5.8\*10\^12 cells/L) and reticulocyte count (\<0.38 or \>2.64 percentage of reticulocytes). Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became normal, are recorded in "To Normal or NC" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
Time frame: Up to Day 28
Part A: Number of Participants With Abnormal Urinalysis Parameters
Urine samples were collected from participants for analyzing the following urine parameters: potential of hydrogen (pH) and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Urine samples showing any abnormality were sent for microscopic examination to detect the presence of RBC, WBC, cellular casts, granular casts, hyaline casts, and were counted as cells per high-power field (cells/HPF). Number of participants with abnormal urinalysis result by microscopic examination have been presented.
Time frame: Up to Day 193
Part B: Number of Participants With Abnormal Urinalysis Parameters
Urine samples were planned to be collected to analyze urine parameters.
Time frame: Up to Day 30
Part C: Number of Participants With Abnormal Urinalysis Parameters
Urine samples were collected from participants for analyzing the following urine parameters: pH and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Urine samples showing any abnormality were sent for microscopic examination to detect the presence of RBC, WBC, cellular casts, granular casts, hyaline casts, and were counted as cells/HPF. Number of participants with abnormal urinalysis result by microscopic examination have been presented.
Time frame: Up to Day 28
Part A: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs included systolic blood pressure(SBP), diastolic blood pressure(DBP), heart rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (millimeters of mercury \[mmHg\]): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute): \<11(low) or \>20(high) and body temperature (degrees Celsius) \<35.5 (low) or \>38.0 (high). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%.
Time frame: Up to Day 193
Part B: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
Time frame: Up to Day 30
Part C: Number of Participants With Worst Case Vital Sign Results by PCI Criteria Post-Baseline Relative to Baseline
Vital signs included SBP, DBP, heart rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (mmHg): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute): \<11 (low) or \>20 (high) and body temperature (degrees Celsius) \<35.5 (low) or \>38.0 (high). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%.
Time frame: Up to Day 49
Part A: Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Time frame: Up to Day 193
Part B: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and QTcF.
Time frame: Up to Day 30
Part C: Number of Participants With Worst Case Post-Baseline Abnormal ECG Findings
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTcF intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
Time frame: Up to Day 28
Part A: Plasma Concentrations of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. Pharmacokinetic (PK) parameters were calculated using standard non-compartmental analysis. PK Population consisted of all participants in the Safety Population who received an active dose and for whom a PK sample was obtained and analyzed.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: Plasma Concentrations of GSK3358699
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: Plasma Concentrations of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: AUC(0-t) of GSK3358699
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: AUC(0-t) of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: AUC(0-infinity) of GSK3358699
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: AUC(0-infinity) of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
Part B: AUC(0-24) of GSK3358699
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
Part C: AUC(0-24) of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Part A: Maximum Plasma Concentration (Cmax) of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: Cmax of GSK3358699
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: Cmax of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: Time to Cmax (Tmax) of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: Tmax of GSK3358699
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: Tmax of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: Apparent Terminal Phase Half-life (t1/2) of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: t1/2 of GSK3358699
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: t1/2 of GSK3358699
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: Plasma Concentrations of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: Plasma Concentrations of GSK3206944
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: Plasma Concentrations of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Days 4, 8 and 12: Pre-dose; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: AUC(0-t) of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: AUC(0-t) of GSK3206944
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: AUC(0-t) of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: AUC(0-infinity) of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: AUC(0-infinity) of GSK3206944
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: AUC(0-infinity) of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: AUC(0-24) of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
Part B: AUC(0-24) of GSK3206944
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours post-dose in each treatment period
Part C: AUC(0-24) of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Days 1 and 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
Part A: Cmax of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: Cmax of GSK3206944
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: Cmax of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: Tmax of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: Tmax of GSK3206944
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: Tmax of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: t1/2 of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part B: t1/2 of GSK3206944
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose in each treatment period
Part C: t1/2 of GSK3206944
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12 and 24 hours; Day 14: Pre-dose, 15 minutes, 30 minutes, 1, 2, 4, 6, 8, 12, 24 and 48 hours post-dose
Part A: Monocyte Intracellular Concentration of GSK3206944
Blood samples were collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period
Part B: Monocyte Intracellular Concentration of GSK3206944
Blood samples were planned to be collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes. GSK3206944 is a metabolite of GSK3358699.
Time frame: Day 1: 1, 4, 8, 24 and 48 hours post-dose in each treatment period
Part C: Monocyte Intracellular Concentration of GSK3206944
Blood samples were collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes. GSK3206944 is a metabolite of GSK3358699.
Time frame: Days 1 and 13: 1, 4 and 8 hour; Days 4, 8 and 12: Pre-dose; Day 14: 1, 4, 8, 24 and 48 hours post-dose
Part A: Absolute Values of Monocyte Chemotactic Protein (MCP)-1, Interleukin (IL)6, Tumor Necrosis Factor (TNF) Alpha in Blood After Ex-vivo Lipopolysaccharide (LPS) Activation
Whole blood samples of 1 milliliter (mL) were collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL-6 and TNF alpha) were analyzed.
Time frame: Day 1: 1, 4, 8, 12, 24 and 48 hours
Part B: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation
Whole blood samples were planned to be collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL6 and TNF alpha) were planned to be analyzed.
Time frame: Day 1: 1, 4, 8, 12, 24 and 48 hours
Part C: Absolute Values of MCP-1, IL6, TNF Alpha in Blood After Ex-vivo LPS Activation
Whole blood samples of 1 mL were collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL-6 and TNF alpha) were analyzed.
Time frame: Day 1: 1, 4 and 8 hours; Days 2, 4, 8 and 12: Pre-dose; Day 13: Pre-dose, 1, 4 and 8 hours; Day 14: Pre-dose, Pre-LPS challenge, 1, 4, 8, 24 and 48 hours
This was a randomized, double-blind, placebo-controlled, 3-part study. Part A was single ascending dose crossover with 2 interlocking cohorts(1 and 2);Part B was planned to be a single dose, open-label, 2-way crossover in fed, fasted conditions(Cohort3);Part C was repeat dose design in sequential cohorts(4,5) and cohorts 6 to 8 were planned.
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 2 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 2 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Protocol defined stopping criteria | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 2 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 2 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 1 | 2 | 1 | 2 | 1 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 1 | 2 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Protocol violation | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 1 | 2 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 1 | 2 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 1 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 14 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 9 | 12 | 0 | 0 | 0 |
| Withdrew: Study closed/terminated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 9 | 0 | 0 | 0 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 | 0 |
An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed before. Safety Population consisted of all randomized participants who took at least 1 dose of study treatment.
| Participants | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|---|
| AEs | 8 | 2 | 3 | 2 | 3 | 8 | 4 | 3 |
| SAEs | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed before.
No measurements were reported for this outcome.
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, important medical events that may jeopardize the participant or require medical or surgical intervention to prevent one of the outcomes listed before.
| Participants | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|
| AEs | 7 | 8 | — | — | — |
| SAEs | 0 | 1 | — | — | — |
Blood samples were collected for analysis of clinical chemistry parameters. PCI ranges were \<30 grams per liter (g/L) (albumin), \<2 or \>2.75 millimoles/L (mmol/L) (calcium), \>1.3\* upper limit of normal (ULN) mmol/L (creatinine), \<3 or \>9 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), and \<130 or \>150 mmol/L (sodium). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change (NC) category. Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100%.
| Participants | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|---|
| Albumin: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Albumin: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Albumin: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Calcium: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Calcium: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Calcium: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Creatinine: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Creatinine: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Creatinine: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glucose: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Glucose: To within Range or No Change | 22 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Glucose: To High | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Potassium: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Potassium: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Potassium: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Sodium: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Sodium: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Sodium: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Clinical chemistry parameters assessed were alanine aminotransferase(ALT)(\<10 or \>50 international units per liter\[IU/L\]),alkaline phosphatase(ALP)(\<40 or \>129 IU/L),aspartate aminotransferase(AST)(\<0 or \>37 IU/L),cholesterol(\<2.3 or \>4.9 mmol/L),direct bilirubin(DB)(\<0 or \>5 micromoles\[mcmol\]/L),high density lipoprotein (DL)(\<0.9 or \>1.5 mmol/L),C-reactive protein(CRP)(\<0.0 or \>5.0mg/liter),low DL(\<0 or \>3.0 mmol/L), total bilirubin (\<0 or \>20 mcmol/L),total protein(\<63 or \>83 grams/L),triglycerides(\<0 or \>2.3 mmol/L) and blood urea nitrogen(BUN)(\<4.76 or \>23.24 mg/deciliter).Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category.Participants whose laboratory value category was unchanged(e.g.,High to High) or whose value became normal, are recorded in "To Normal or NC" category.Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
| Participants | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|---|
| ALT: To Low,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| ALT: To Normal or NC,n=23,5,3,6,6,12,6,6 | 22 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| ALT: To High,n=23,5,3,6,6,12,6,6 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| ALP: To Low,n=23,5,3,6,6,12,6,6 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| ALP: To Normal or NC,n=23,5,3,6,6,12,6,6 | 23 | 4 | 3 | 6 | 6 | 12 | 6 | 6 |
| ALP: To High,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| AST: To Low,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| AST: To Normal or NC,n=23,5,3,6,6,12,6,6 | 22 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| AST: To High,n=23,5,3,6,6,12,6,6 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cholesterol: To Low,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Cholesterol: To Normal or NC,n=23,5,3,6,6,12,6,6 | 22 | 4 | 3 | 5 | 5 | 10 | 5 | 4 |
| Cholesterol: To High,n=23,5,3,6,6,12,6,6 | 1 | 1 | 0 | 1 | 1 | 2 | 1 | 2 |
| DB: To Low,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| DB:To Normal or NC,n=23,5,3,6,6,12,6,6 | 22 | 5 | 2 | 6 | 6 | 12 | 6 | 6 |
| DB: To High,n=23,5,3,6,6,12,6,6 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| High DL: To Low,n=23,5,3,6,6,12,6,6 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 0 |
| High DL:To Normal or NC,n=23,5,3,6,6,12,6,6 | 22 | 2 | 3 | 5 | 6 | 11 | 6 | 6 |
| High DL: To High,n=23,5,3,6,6,12,6,6 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 |
| CRP: To Low,n=23,5,3,6,4,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| CRP: To Normal or NC,n=23,5,3,6,4,12,6,6 | 18 | 5 | 2 | 6 | 4 | 4 | 6 | 5 |
| CRP: To High,n=23,5,3,6,4,12,6,6 | 5 | 0 | 1 | 0 | 0 | 8 | 0 | 1 |
| Low DL: To Low,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Low DL: To Normal or NC,n=23,5,3,6,6,12,6,6 | 21 | 5 | 2 | 4 | 5 | 11 | 5 | 4 |
| Low DL: To High,n=23,5,3,6,6,12,6,6 | 2 | 0 | 1 | 2 | 1 | 1 | 1 | 2 |
| Total bilirubin: To Low,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total bilirubin:ToNormal or NC,n=23,5,3,6,6,12,6,6 | 22 | 5 | 3 | 6 | 6 | 11 | 6 | 6 |
| Total bilirubin: To High,n=23,5,3,6,6,12,6,6 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Total protein: To Low,n=23,5,3,6,6,12,6,6 | 4 | 0 | 1 | 0 | 2 | 3 | 1 | 1 |
| Total protein:To Normal or NC,n=23,5,3,6,6,12,6,6 | 19 | 5 | 2 | 6 | 4 | 9 | 5 | 5 |
| Total protein: To High,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Triglycerides: To Low,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Triglycerides:To Normal or NC,n=23,5,3,6,6,12,6,6 | 17 | 3 | 2 | 4 | 4 | 12 | 3 | 4 |
| Triglycerides: To High,n=23,5,3,6,6,12,6,6 | 6 | 2 | 1 | 2 | 2 | 0 | 3 | 2 |
| BUN: To Low,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| BUN: To Normal or NC,n=23,5,3,6,6,12,6,6 | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| BUN: To High,n=23,5,3,6,6,12,6,6 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Blood samples were planned to be collected to analyze the chemistry parameters.
No measurements were reported for this outcome.
Blood samples were planned to be collected to analyze the chemistry parameters.
No measurements were reported for this outcome.
Blood samples were collected for analysis of chemistry parameters. PCI ranges were \<30 g/L (albumin), \<2 or \>2.75 mmol/L (calcium), \>1.3\* ULN mmol/L (creatinine), \<3 or \>9 mmol/L (glucose), \<3 or \>5.5 mmol/L (potassium), and \<130 or \>150 mmol/L (sodium). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if participant had values that changed To Low and To High, so the percentages may not add to 100%.
| Participants | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|
| Albumin: To Low | 0 | 0 | — | — | — |
| Albumin: To within Range or No Change | 11 | 14 | — | — | — |
| Albumin: To High | 0 | 0 | — | — | — |
| Calcium: To Low | 0 | 0 | — | — | — |
| Calcium: To within Range or No Change | 11 | 14 | — | — | — |
| Calcium: To High | 0 | 0 | — | — | — |
| Creatinine: To Low | 0 | 0 | — | — | — |
| Creatinine: To within Range or No Change | 11 | 14 | — | — | — |
| Creatinine: To High | 0 | 0 | — | — | — |
| Glucose: To Low | 0 | 0 | — | — | — |
| Glucose: To within Range or No Change | 11 | 14 | — | — | — |
| Glucose: To High | 0 | 0 | — | — | — |
| Potassium: To Low | 0 | 0 | — | — | — |
| Potassium: To within Range or No Change | 11 | 14 | — | — | — |
| Potassium: To High | 0 | 0 | — | — | — |
| Sodium: To Low | 0 | 0 | — | — | — |
| Sodium: To within Range or No Change | 11 | 14 | — | — | — |
| Sodium: To High | 0 | 0 | — | — | — |
Clinical chemistry parameters assessed were ALT (\<10 or \>50 IU/L), ALP (\<40 or \>129 IU/L), AST (\<0 or \>37 IU/L), cholesterol (\<2.3 or \>4.9 mmol/L), DB (\<0 or \>5 mcmol/L), high DL (\<0.9 or \>1.5 mmol/L), CRP (\<0.0 or \>5.0 mg/liter), low DL (\<0 or \>3.0 mmol/L), total bilirubin (\<0 or \>20 mcmol/L), total protein (\<63 or \>83 grams/L), triglycerides (\<0 or \>2.3 mmol/L) and BUN (\<4.76 or \>23.24 mg/deciliter). Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became normal, are recorded in "To Normal or NC" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
| Participants | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|
| ALT: To Low,n=11,14,0,0,0 | 0 | 1 | — | — | — |
| ALT: To Normal or NC,n=11,14,0,0,0 | 11 | 12 | — | — | — |
| ALT: To High,n=11,14,0,0,0 | 0 | 1 | — | — | — |
| ALP: To Low,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| ALP: To Normal or NC,n=11,14,0,0,0 | 11 | 14 | — | — | — |
| ALP: To High,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| AST: To Low,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| AST: To Normal or NC,n=11,14,0,0,0 | 10 | 14 | — | — | — |
| AST: To High,n=11,14,0,0,0 | 1 | 0 | — | — | — |
| Cholesterol: To Low,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| Cholesterol: To Normal or NC,n=11,14,0,0,0 | 9 | 13 | — | — | — |
| Cholesterol: To High,n=11,14,0,0,0 | 2 | 1 | — | — | — |
| DB: To Low,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| DB:To Normal or NC,n=11,14,0,0,0 | 11 | 14 | — | — | — |
| DB: To High,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| High DL: To Low,n=11,14,0,0,0 | 1 | 1 | — | — | — |
| High DL:To Normal or NC,n=11,14,0,0,0 | 10 | 13 | — | — | — |
| High DL: To High,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| CRP: To Low,n=10,13,0,0,0 | 0 | 0 | — | — | — |
| CRP: To Normal or NC,n=10,13,0,0,0 | 9 | 12 | — | — | — |
| CRP: To High,n=10,13,0,0,0 | 1 | 1 | — | — | — |
| Low DL: To Low,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| Low DL: To Normal or NC,n=11,14,0,0,0 | 8 | 13 | — | — | — |
| Low DL: To High,n=11,14,0,0,0 | 3 | 1 | — | — | — |
| Total bilirubin: To Low,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| Total bilirubin:ToNormal or NC,n=11,14,0,0,0 | 11 | 14 | — | — | — |
| Total bilirubin: To High,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| Total protein: To Low,n=11,14,0,0,0 | 1 | 2 | — | — | — |
| Total protein:To Normal or NC,n=11,14,0,0,0 | 10 | 12 | — | — | — |
| Total protein: To High,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| Triglycerides: To Low,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| Triglycerides:To Normal or NC,n=11,14,0,0,0 | 10 | 13 | — | — | — |
| Triglycerides: To High,n=11,14,0,0,0 | 1 | 1 | — | — | — |
| BUN: To Low,n=11,14,0,0,0 | 0 | 0 | — | — | — |
| BUN: To Normal or NC,n=11,14,0,0,0 | 11 | 14 | — | — | — |
| BUN: To High,n=11,14,0,0,0 | 0 | 0 | — | — | — |
Blood samples collected for analysis of hematology parameters. PCI ranges were \>0.54 proportion of red blood cells in blood (hematocrit), \>180 grams/liter (hemoglobin), \<0.8 \*10\^9 cells/L (lymphocyte count), \<1.5 \*10\^9 cells/L (total absolute neutrophil count \[ANC\]), \<100 or \>550 \*10\^9 cells/L (platelet count), and \<3 or \>20\*10\^9 cells/L (white blood cell \[WBC\] count). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant had values that changed To Low and To High, so the percentages may not add to 100%.
| Participants | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|---|
| Hematocrit: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hematocrit: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Hematocrit: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hemoglobin: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hemoglobin: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Hemoglobin: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Lymphocyte count: To Low | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Lymphocyte count: To within Range or No Change | 21 | 5 | 3 | 6 | 6 | 10 | 6 | 6 |
| Lymphocyte count: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Platelet count: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Platelet count: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Platelet count: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total ANC: To Low | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Total ANC: To within Range or No Change | 23 | 4 | 3 | 6 | 6 | 12 | 6 | 6 |
| Total ANC: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| WBC: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| WBC: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| WBC: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Hematology parameters assessed were activated partial thromboplastin time (APTT) (\<25 or \>37 seconds), basophil count (\<0.0 or \>0.1\*10\^9 cells/L), eosinophil count (\<0.0 or \>0.4\*10\^9 cells/L), fibrinogen (\<1.5 or \>4.0 g/L), mean corpuscle hemoglobin (MCH) (\<26.0 or \>33.5 picogram), mean corpuscle volume (MCV) (\<80 or \>99 femtoliter), monocyte count (\<0.2 or \>1.0\*10\^9 cells/L), prothrombin time (PT) (\<10 or \>12 seconds), red blood cell (RBC) count (\<4.4 or \>5.8\*10\^12 cells/L) and reticulocyte count (\<0.38 or \>2.64 percentage of reticulocytes). Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became normal, are recorded in "To Normal or NC" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
| Participants | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|---|
| APTT: To Low | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| APTT: To Normal or NC | 21 | 5 | 2 | 6 | 4 | 11 | 6 | 4 |
| APTT: To High | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 2 |
| Basophil count: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Basophil count: To Normal or NC | 23 | 5 | 3 | 6 | 5 | 12 | 6 | 6 |
| Basophil count: To High | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Eosinophil count: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Eosinophil count: To Normal or NC | 21 | 5 | 3 | 6 | 5 | 12 | 6 | 5 |
| Eosinophil count: To High | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 1 |
| Fibrinogen: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Fibrinogen: To Normal or NC | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 5 |
| Fibrinogen: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| MCH: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| MCH: To Normal or NC | 23 | 4 | 3 | 6 | 6 | 12 | 6 | 6 |
| MCH: To High | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| MCV: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| MCV: To Normal or NC | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| MCV: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Monocyte count: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Monocyte count: To Normal or NC | 19 | 5 | 3 | 6 | 6 | 6 | 6 | 6 |
| Monocyte count: To High | 4 | 0 | 0 | 0 | 0 | 6 | 0 | 0 |
| PT: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| PT: To Normal or NC | 23 | 5 | 2 | 6 | 6 | 12 | 6 | 5 |
| PT: To High | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 |
| RBC: To Low | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| RBC: To Normal or NC | 22 | 5 | 2 | 6 | 6 | 12 | 6 | 6 |
| RBC: To High | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Reticulocyte count: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Reticulocyte count: To Normal or NC | 23 | 4 | 3 | 6 | 6 | 12 | 6 | 6 |
| Reticulocyte count: To High | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Blood samples were planned to be collected to analyze hematology parameters.
No measurements were reported for this outcome.
Blood samples were planned to be collected to analyze hematology parameters.
No measurements were reported for this outcome.
Blood samples were collected for analysis of hematology parameters. PCI ranges were \>0.54 proportion of red blood cells in blood (hematocrit), \>180 grams/liter (hemoglobin), \<0.8\*10\^9 cells/L (lymphocyte count), \<1.5\*10\^9 cells/L (total ANC), \<100 or \>550\*10\^9 cells/L (platelet count), and \<3 or \>20\*10\^9 cells/L (WBC count). Participants were counted in worst case category that their value changes to (low, within range or no change or high), unless there is no change in their category. Participants whose laboratory value category was unchanged (e.g., High to High), or whose value became within range, were recorded in To within Range or No Change category. Participants were counted twice if the participant had values that changed To Low and To High, so the percentages may not add to 100%.
| Participants | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|
| Hematocrit: To Low | 0 | 0 | — | — | — |
| Hematocrit: To within Range or No Change | 11 | 14 | — | — | — |
| Hematocrit: To High | 0 | 0 | — | — | — |
| Hemoglobin: To Low | 0 | 0 | — | — | — |
| Hemoglobin: To within Range or No Change | 11 | 14 | — | — | — |
| Hemoglobin: To High | 0 | 0 | — | — | — |
| Lymphocyte count: To Low | 1 | 0 | — | — | — |
| Lymphocyte count: To within Range or No Change | 10 | 14 | — | — | — |
| Lymphocyte count: To High | 0 | 0 | — | — | — |
| Platelet count: To Low | 0 | 0 | — | — | — |
| Platelet count: To within Range or No Change | 11 | 14 | — | — | — |
| Platelet count: To High | 0 | 0 | — | — | — |
| Total ANC: To Low | 1 | 0 | — | — | — |
| Total ANC: To within Range or No Change | 10 | 14 | — | — | — |
| Total ANC: To High | 0 | 0 | — | — | — |
| WBC: To Low | 1 | 1 | — | — | — |
| WBC: To within Range or No Change | 10 | 13 | — | — | — |
| WBC: To High | 0 | 0 | — | — | — |
Hematology parameters assessed were APTT (\<25 or \>37 seconds), basophil count (\<0.0 or \>0.1\*10\^9 cells/L), eosinophil count (\<0.0 or \>0.4\*10\^9 cells/L), fibrinogen (\<1.5 or \>4.0 g/L), MCH (\<26.0 or \>33.5 picogram), MCV (\<80 or \>99 femtoliter), monocyte count (\<0.2 or \>1.0\*10\^9 cells/L), PT (\<10 or \>12 seconds), RBC count (\<4.4 or \>5.8\*10\^12 cells/L) and reticulocyte count (\<0.38 or \>2.64 percentage of reticulocytes). Participants were counted in worst case category that their value changes to (low, normal or high), unless there is NC in their category. Participants whose laboratory value category was unchanged (e.g., High to High) or whose value became normal, are recorded in "To Normal or NC" category. Participants were counted twice if participant had values that changed To Low and To High, so percentages may not add to 100%.
| Participants | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|
| APTT: To Low | 1 | 0 | — | — | — |
| APTT: To Normal or NC | 10 | 13 | — | — | — |
| APTT: To High | 0 | 1 | — | — | — |
| Basophil count: To Low | 0 | 0 | — | — | — |
| Basophil count: To Normal or NC | 11 | 14 | — | — | — |
| Basophil count: To High | 0 | 0 | — | — | — |
| Eosinophil count: To Low | 0 | 0 | — | — | — |
| Eosinophil count: To Normal or NC | 11 | 14 | — | — | — |
| Eosinophil count: To High | 0 | 0 | — | — | — |
| Fibrinogen: To Low | 0 | 0 | — | — | — |
| Fibrinogen: To Normal or NC | 11 | 14 | — | — | — |
| Fibrinogen: To High | 0 | 0 | — | — | — |
| MCH: To Low | 0 | 0 | — | — | — |
| MCH: To Normal or NC | 11 | 14 | — | — | — |
| MCH: To High | 0 | 0 | — | — | — |
| MCV: To Low | 0 | 0 | — | — | — |
| MCV: To Normal or NC | 11 | 14 | — | — | — |
| MCV: To High | 0 | 0 | — | — | — |
| Monocyte count: To Low | 0 | 0 | — | — | — |
| Monocyte count: To Normal or NC | 11 | 14 | — | — | — |
| Monocyte count: To High | 0 | 0 | — | — | — |
| PT: To Low | 0 | 0 | — | — | — |
| PT: To Normal or NC | 10 | 14 | — | — | — |
| PT: To High | 1 | 0 | — | — | — |
| RBC: To Low | 0 | 1 | — | — | — |
| RBC: To Normal or NC | 11 | 13 | — | — | — |
| RBC: To High | 0 | 0 | — | — | — |
| Reticulocyte count: To Low | 0 | 0 | — | — | — |
| Reticulocyte count: To Normal or NC | 11 | 14 | — | — | — |
| Reticulocyte count: To High | 0 | 0 | — | — | — |
Urine samples were collected from participants for analyzing the following urine parameters: potential of hydrogen (pH) and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Urine samples showing any abnormality were sent for microscopic examination to detect the presence of RBC, WBC, cellular casts, granular casts, hyaline casts, and were counted as cells per high-power field (cells/HPF). Number of participants with abnormal urinalysis result by microscopic examination have been presented.
| Participants | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|---|
| RBC | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| WBC | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Cellular casts | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Granular casts | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hyaline casts | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Urine samples were planned to be collected to analyze urine parameters.
No measurements were reported for this outcome.
Urine samples were collected from participants for analyzing the following urine parameters: pH and glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocytes levels by dipstick. Urine samples showing any abnormality were sent for microscopic examination to detect the presence of RBC, WBC, cellular casts, granular casts, hyaline casts, and were counted as cells/HPF. Number of participants with abnormal urinalysis result by microscopic examination have been presented.
| Participants | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|
| RBC | 0 | 0 | — | — | — |
| WBC | 1 | 1 | — | — | — |
| Cellular casts | 0 | 0 | — | — | — |
| Granular casts | 0 | 0 | — | — | — |
| Hyaline casts | 0 | 0 | — | — | — |
Vital signs included systolic blood pressure(SBP), diastolic blood pressure(DBP), heart rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (millimeters of mercury \[mmHg\]): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute): \<11(low) or \>20(high) and body temperature (degrees Celsius) \<35.5 (low) or \>38.0 (high). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%.
| Participants | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|---|
| SBP: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| SBP: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| SBP: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| DBP: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| DBP: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| DBP: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Heart rate: To Low | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Heart rate: To within Range or No Change | 23 | 5 | 3 | 6 | 6 | 12 | 6 | 6 |
| Heart rate: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Respiratory rate: To Low | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Respiratory rate: To within Range or No Change | 22 | 5 | 3 | 6 | 6 | 11 | 6 | 6 |
| Respiratory rate: To High | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Body temperature: To Low | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Body temperature: To within Range or No Change | 22 | 5 | 3 | 5 | 6 | 11 | 6 | 6 |
| Body temperature: To High | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Vital signs were planned to be measured in a semi-supine position after 5 minutes of rest.
No measurements were reported for this outcome.
Vital signs included SBP, DBP, heart rate, respiratory rate and body temperature and were measured in a semi-supine position after 5 minutes rest. PCI ranges were, SBP (mmHg): \<85 (low) or \>160 (high), DBP (mmHg): \<45 (low) or \>100 (high), heart rate (beats per minute): \<40 (low) or \>110 (high), respiration rate (breaths per minute): \<11 (low) or \>20 (high) and body temperature (degrees Celsius) \<35.5 (low) or \>38.0 (high). Participants were counted in the worst case category that their value changes to (low, within range or no change, or high), unless there is no change in their category. Participants whose vital signs value category was unchanged (e.g., High to High), or whose value became within range, were recorded in the "To within Range or No Change" category. Participants were counted twice if the participant had values that changed "To Low" and "To High", so the percentages may not add to 100%.
| Participants | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|
| SBP: To Low | 0 | 0 | — | — | — |
| SBP: To within Range or No Change | 11 | 14 | — | — | — |
| SBP: To High | 0 | 0 | — | — | — |
| DBP: To Low | 0 | 0 | — | — | — |
| DBP: To within Range or No Change | 11 | 14 | — | — | — |
| DBP: To High | 0 | 0 | — | — | — |
| Heart rate: To Low | 0 | 1 | — | — | — |
| Heart rate: To within Range or No Change | 10 | 13 | — | — | — |
| Heart rate: To High | 1 | 0 | — | — | — |
| Respiratory rate: To Low | 1 | 1 | — | — | — |
| Respiratory rate: To within Range or No Change | 9 | 13 | — | — | — |
| Respiratory rate: To High | 1 | 0 | — | — | — |
| Body temperature: To Low | 0 | 0 | — | — | — |
| Body temperature: To within Range or No Change | 11 | 14 | — | — | — |
| Body temperature: To High | 0 | 0 | — | — | — |
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QT interval corrected using the Fridericia's formula (QTcF) intervals. Abnormal findings were categorized as clinically significant (CS) and not clinically significant (NCS). Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
| Participants | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|---|
| Abnormal - not clinically significant | 6 | 1 | 0 | 0 | 3 | 2 | 3 | 0 |
| Abnormal - clinically significant | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Twelve lead ECGs were planned to be performed to measure PR interval, QRS duration, QT interval and QTcF.
No measurements were reported for this outcome.
Twelve lead ECGs were obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and QTcF intervals. Abnormal findings were categorized as clinically significant and not clinically significant. Clinically significant abnormal findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition. Data for number of participants with worst case post-Baseline abnormal ECG findings have been presented.
| Participants | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|
| Abnormal - not clinically significant | 2 | 3 | — | — | — |
| Abnormal - clinically significant | 0 | 1 | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. Pharmacokinetic (PK) parameters were calculated using standard non-compartmental analysis. PK Population consisted of all participants in the Safety Population who received an active dose and for whom a PK sample was obtained and analyzed.
| Nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Pre-dose, n=5,3,6,6,12,6,6 | 0.0000 (0.000 to 0.000) | 0.0000 (0.000 to 0.000) | 0.0000 (0.000 to 0.000) | 0.0000 (0.0000 to 0.000) | 0.0000 (0.0000 to 0.0000) | 0.0000 (0.0000 to 0.0000) | 0.0000 (0.0000 to 0.0000) |
| 15 minutes, n=5,3,6,6,12,6,6 | 0.4950 (0.000 to 1.921) | 0.6470 (0.431 to 1.142) | 1.0480 (0.000 to 10.565) | 0.5390 (0.000 to 16.637) | 0.2620 (0.000 to 15.086) | 5.8460 (0.189 to 21.540) | 0.9245 (0.000 to 3.315) |
| 30 minutes, n=5,3,6,6,12,6,6 | 0.6840 (0.497 to 1.106) | 1.9510 (1.094 to 2.411) | 6.4560 (3.010 to 10.780) | 5.1050 (1.017 to 28.795) | 5.9130 (0.726 to 22.813) | 64.4810 (8.884 to 99.800) | 33.2120 (1.966 to 211.754) |
| 1 hour, n=5,3,6,6,12,6,6 | 0.4210 (0.264 to 0.553) | 0.9960 (0.893 to 1.440) | 3.5150 (1.234 to 8.072) | 9.1840 (4.283 to 18.108) | 11.0785 (2.165 to 17.950) | 28.4500 (20.421 to 92.656) | 28.8380 (15.838 to 39.777) |
| 2 hours, n=5,3,6,6,12,6,6 | 0.1810 (0.119 to 0.215) | 0.4790 (0.284 to 0.651) | 1.6930 (0.638 to 2.067) | 4.8100 (2.093 to 8.048) | 6.9495 (3.397 to 26.662) | 10.6550 (6.792 to 18.163) | 8.6735 (7.895 to 18.906) |
| 4 hours, n=5,2,6,6,12,6,6 | NA (NA to NA) | 0.1560 (0.151 to 0.161) | 0.5265 (0.358 to 0.916) | 1.2865 (0.746 to 1.599) | 1.9095 (1.158 to 4.344) | 3.6390 (1.706 to 4.101) | 2.5920 (1.886 to 4.266) |
| 6 hours, n=5,3,6,6,12,6,6 | NA (NA to NA) | NA (NA to NA) | 0.3160 (0.243 to 0.792) | 0.6720 (0.385 to 1.327) | 1.1020 (0.409 to 2.342) | 1.4305 (0.916 to 3.954) | 1.2515 (0.980 to 1.748) |
| 8 hours, n=5,3,6,6,12,6,6 | NA (NA to NA) | NA (NA to NA) | 0.2120 (0.110 to 0.426) | 0.3775 (0.209 to 0.611) | 0.5915 (0.230 to 1.131) | 0.8340 (0.318 to 1.720) | 0.6665 (0.434 to 1.033) |
| 12 hours, n=5,3,2,6,12,6,6 | NA (NA to NA) | NA (NA to NA) | 0.1390 (0.136 to 0.142) | 0.1490 (0.100 to 0.159) | 0.2510 (0.145 to 0.605) | 0.5195 (0.291 to 0.745) | 0.4255 (0.145 to 0.939) |
| 24 hours, n=5,3,6,6,9,4,5 | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | 0.1510 (0.000 to 0.369) | 0.1250 (0.000 to 0.485) | 0.2090 (0.000 to 0.287) |
| 48 hours, n=5,3,6,6,6,6,6 | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | 0.0000 (0.000 to 0.114) | NA (NA to NA) | NA (NA to NA) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1:Pre-dose,n=14,0,0,0 | 0.0000 (0.000 to 0.000) | — | — | — |
| Day 1:15 minutes,n=14,0,0,0 | 0.2825 (0.000 to 13.601) | — | — | — |
| Day 1:30 minutes,n=14,0,0,0 | 5.7430 (0.914 to 16.960) | — | — | — |
| Day 1:1 hour,n=14,0,0,0 | 3.8955 (1.758 to 12.384) | — | — | — |
| Day 1:2 hours,n=14,0,0,0 | 1.3365 (0.826 to 4.710) | — | — | — |
| Day 1:4 hours,n=14,0,0,0 | 0.5730 (0.205 to 0.922) | — | — | — |
| Day 1:6 hours,n=14,0,0,0 | 0.2940 (0.109 to 0.500) | — | — | — |
| Day 1:8 hours,n=10,0,0,0 | 0.1690 (0.109 to 0.384) | — | — | — |
| Day 1:12 hours,n=3,0,0,0 | 0.1390 (0.120 to 0.144) | — | — | — |
| Day 1:24 hours,n=14,0,0,0 | NA (NA to NA) | — | — | — |
| Day 4: Pre-dose,n=1,0,0,0 | 0.0000 (0.000 to 0.000) | — | — | — |
| Day 8: Pre-dose,n=2,0,0,0 | 0.0000 (0.000 to 0.000) | — | — | — |
| Day 12: Pre-dose,n=4,0,0,0 | NA (NA to NA) | — | — | — |
| Day 14:Pre-dose,n=2,0,0,0 | NA (NA to NA) | — | — | — |
| Day 14:15 minutes,n=2,0,0,0 | 4.3390 (1.836 to 6.842) | — | — | — |
| Day 14:30 minutes,n=2,0,0,0 | 6.0065 (4.658 to 7.355) | — | — | — |
| Day 14:1 hour,n=2,0,0,0 | 3.0170 (2.233 to 3.801) | — | — | — |
| Day 14:2 hours,n=2,0,0,0 | 1.4905 (0.979 to 2.002) | — | — | — |
| Day 14:4 hours,n=2,0,0,0 | 0.8295 (0.754 to 0.905) | — | — | — |
| Day 14:6 hours,n=2,0,0,0 | 0.6360 (0.313 to 0.959) | — | — | — |
| Day 14:8 hours,n=2,0,0,0 | 0.3920 (0.155 to 0.629) | — | — | — |
| Day 14:12 hours,n=1,0,0,0 | 0.2730 (0.273 to 0.273) | — | — | — |
| Day 14:24 hours,n=2,0,0,0 | NA (NA to NA) | — | — | — |
| Day 14:48 hours,n=2,0,0,0 | NA (NA to NA) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours*nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: Area Under the Plasma Concentration Curve From Time Zero to Last Time of Quantifiable Concentration (AUC[0-t]) of GSK3358699 | 0.74 (0.6 to 1.3) | 2.33 (1.7 to 2.8) | 10.77 (5.1 to 16.4) | 23.40 (18.1 to 30.5) | 31.88 (27.2 to 56.0) | 66.38 (54.6 to 128.1) | 58.09 (48.1 to 114.3) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours*nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=14,0,0,0 | 9.47 (4.8 to 20.9) | — | — | — |
| Day 14, n=2,0,0,0 | 11.70 (7.6 to 15.8) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours*nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: Area Under the Plasma Concentration Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3358699 | NA (NA to NA) | NA (NA to NA) | 13.20 (5.6 to 17.0) | 23.89 (18.6 to 31.0) | 33.22 (28.4 to 57.0) | 69.13 (56.6 to 129.0) | 59.68 (49.2 to 114.7) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours*nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=7,0,0,0 | 9.07 (5.9 to 16.9) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours*nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours (AUC[0-24]) of GSK3358699 | NA (NA to NA) | NA (NA to NA) | 13.17 (5.6 to 16.9) | 23.86 (18.6 to 31.0) | 32.69 (25.4 to 56.0) | 67.38 (56.4 to 128.1) | 59.05 (48.1 to 114.7) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours*nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=7,0,0,0 | 9.07 (5.8 to 16.9) | — | — | — |
| Day 14, n=1,0,0,0 | 7.99 (NA to NA) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: Maximum Plasma Concentration (Cmax) of GSK3358699 | 0.68 (0.5 to 1.9) | 1.95 (1.4 to 2.4) | 6.46 (3.0 to 10.8) | 16.10 (9.1 to 28.8) | 17.47 (7.5 to 26.7) | 64.48 (20.4 to 99.8) | 34.58 (20.4 to 211.8) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=14,0,0,0 | 6.19 (2.6 to 17.0) | — | — | — |
| Day 14, n=2,0,0,0 | 6.01 (4.7 to 7.4) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: Time to Cmax (Tmax) of GSK3358699 | 0.50 (0.3 to 1.0) | 0.50 (0.5 to 1.0) | 0.50 (0.5 to 0.5) | 1.00 (0.3 to 1.0) | 1.00 (0.2 to 2.0) | 0.76 (0.5 to 1.0) | 0.51 (0.5 to 1.1) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=14,0,0,0 | 0.50 (0.3 to 2.0) | — | — | — |
| Day 14, n=2,0,0,0 | 0.53 (0.5 to 0.6) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: Apparent Terminal Phase Half-life (t1/2) of GSK3358699 | NA (NA to NA) | NA (NA to NA) | 2.44 (2.0 to 2.8) | 2.75 (2.0 to 3.4) | 6.02 (2.1 to 18.4) | 4.77 (3.5 to 11.8) | 6.88 (2.1 to 11.1) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3358699. PK parameters were calculated using standard non-compartmental analysis.
| Hours | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=7,0,0,0 | 2.47 (1.4 to 3.0) | — | — | — |
| Day 14, n=1,0,0,0 | 1.57 (NA to NA) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Pre-dose | 0.0000 (0.000 to 0.000) | 0.000 (0.000 to 0.000) | 0.0000 (0.000 to 0.000) | 0.0000 (0.000 to 0.000) | 0.0000 (0.000 to 0.000) | 0.0000 (0.000 to 0.000) | 0.0000 (0.000 to 0.000) |
| 15 minutes | 0.2050 (0.000 to 0.870) | 0.2070 (0.107 to 0.247) | 0.0550 (0.000 to 0.973) | 0.0000 (0.000 to 0.292) | 0.0000 (0.000 to 6.579) | 0.0575 (0.000 to 1.462) | 0.0000 (0.000 to 0.155) |
| 30 minutes | 1.2090 (0.223 to 3.045) | 1.8410 (0.705 to 2.156) | 3.1930 (2.030 to 9.850) | 1.8370 (0.000 to 10.528) | 4.3810 (0.216 to 25.498) | 17.2245 (1.546 to 27.299) | 6.3350 (0.412 to 46.595) |
| 1 hour | 3.0310 (1.808 to 4.898) | 4.2200 (2.505 to 6.026) | 17.1455 (6.453 to 26.263) | 26.1280 (18.350 to 43.603) | 33.6145 (2.943 to 68.271) | 89.1965 (16.207 to 205.963) | 74.5130 (26.229 to 205.962) |
| 2 hours | 3.2830 (2.145 to 4.324) | 5.5640 (4.837 to 7.256) | 17.6535 (7.569 to 30.510) | 46.4250 (27.542 to 82.343) | 70.4010 (20.386 to 105.133) | 102.0865 (51.492 to 161.313) | 121.2220 (88.345 to 231.739) |
| 4 hours | 1.9110 (1.223 to 2.658) | 3.2490 (2.951 to 3.733) | 10.6790 (7.400 to 15.516) | 22.6925 (13.453 to 50.059) | 46.8165 (28.244 to 78.533) | 51.7230 (40.674 to 84.834) | 69.2315 (46.996 to 132.904) |
| 6 hours | 0.9490 (0.529 to 1.342) | 1.5760 (1.532 to 1.877) | 6.7745 (4.726 to 9.175) | 13.7955 (10.716 to 28.908) | 23.1275 (15.320 to 44.082) | 30.4690 (23.891 to 34.815) | 36.8305 (19.883 to 59.881) |
| 8 hours | 0.5840 (0.303 to 0.945) | 1.0200 (1.019 to 1.096) | 4.6515 (2.297 to 5.599) | 8.3535 (6.187 to 14.398) | 13.7165 (9.459 to 21.878) | 16.5795 (10.812 to 21.258) | 18.4825 (12.948 to 31.766) |
| 12 hours | 0.2540 (0.122 to 0.353) | 0.4670 (0.336 to 0.667) | 1.8400 (0.785 to 2.418) | 3.4535 (2.385 to 4.611) | 5.3830 (3.258 to 9.084) | 6.7365 (4.811 to 8.739) | 8.7280 (5.519 to 19.739) |
| 24 hours | 0.0000 (0.000 to 0.118) | 0.1050 (0.000 to 0.113) | 0.2620 (0.136 to 0.626) | 0.4790 (0.348 to 0.577) | 1.2020 (0.598 to 3.960) | 1.1015 (0.630 to 2.452) | 1.5040 (0.471 to 4.065) |
| 48 hours | NA (NA to NA) | NA (NA to NA) | 0.0000 (0.000 to 0.249) | 0.0000 (0.000 to 0.205) | 0.3440 (0.000 to 1.447) | 0.1895 (0.000 to 0.922) | 0.2565 (0.000 to 1.659) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1:Pre-dose,n=14,0,0,0 | 0.0000 (0.000 to 0.000) | — | — | — |
| Day 1:15 minutes,n=14,0,0,0 | 0.0000 (0.000 to 0.459) | — | — | — |
| Day 1:30 minutes,n=14,0,0,0 | 3.1310 (0.116 to 12.947) | — | — | — |
| Day 1:1 hour,n=14,0,0,0 | 19.9335 (5.173 to 38.568) | — | — | — |
| Day 1:2 hours,n=14,0,0,0 | 22.2250 (11.285 to 56.829) | — | — | — |
| Day 1:4 hours,n=14,0,0,0 | 12.7730 (7.948 to 39.355) | — | — | — |
| Day 1:6 hours,n=14,0,0,0 | 7.2920 (4.588 to 18.565) | — | — | — |
| Day 1:8 hours,n=14,0,0,0 | 4.3750 (2.446 to 10.040) | — | — | — |
| Day 1:12 hours,n=14,0,0,0 | 2.2070 (0.883 to 4.176) | — | — | — |
| Day 1:24 hours,n=14,0,0,0 | 0.3805 (0.309 to 1.062) | — | — | — |
| Day 4: Pre-dose,n=14,0,0,0 | 0.5355 (0.000 to 0.890) | — | — | — |
| Day 8: Pre-dose,n=7,0,0,0 | 0.6640 (0.200 to 1.233) | — | — | — |
| Day 12: Pre-dose,n=4,0,0,0 | 0.4945 (0.382 to 1.217) | — | — | — |
| Day 14:Pre-dose,n=2,0,0,0 | 0.5820 (0.549 to 0.615) | — | — | — |
| Day 14:15 minutes,n=2,0,0,0 | 0.7430 (0.582 to 0.904) | — | — | — |
| Day 14:30 minutes,n=2,0,0,0 | 6.4130 (4.906 to 7.920) | — | — | — |
| Day 14:1 hour,n=2,0,0,0 | 15.3355 (14.722 to 15.949) | — | — | — |
| Day 14:2 hours,n=2,0,0,0 | 15.0925 (14.474 to 15.711) | — | — | — |
| Day 14:4 hours,n=2,0,0,0 | 10.4550 (9.880 to 11.030) | — | — | — |
| Day 14:6 hours,n=2,0,0,0 | 6.8500 (5.834 to 7.866) | — | — | — |
| Day 14:8 hours,n=2,0,0,0 | 6.0330 (3.779 to 8.287) | — | — | — |
| Day 14:12 hours,n=2,0,0,0 | 2.2290 (1.424 to 3.034) | — | — | — |
| Day 14:24 hours,n=2,0,0,0 | 0.5275 (0.445 to 0.610) | — | — | — |
| Day 14:48 hours,n=1,0,0,0 | 0.1110 (0.111 to 0.111) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours*nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: AUC(0-t) of GSK3206944 | 15.16 (9.0 to 22.6) | 29.12 (25.0 to 31.6) | 106.55 (73.3 to 143.0) | 209.98 (172.2 to 376.7) | 381.16 (289.5 to 431.4) | 470.40 (403.1 to 706.8) | 630.63 (432.5 to 1030.1) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours*nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=14,0,0,0 | 115.17 (68.7 to 272.0) | — | — | — |
| Day 14, n=2,0,0,0 | 109.71 (94.7 to 124.7) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours*nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: AUC(0-infinity) of GSK3206944 | 17.08 (16.4 to 17.8) | 29.05 (25.7 to 32.4) | 108.29 (74.7 to 144.3) | 189.02 (174.4 to 221.8) | 357.98 (291.8 to 419.1) | 492.92 (408.6 to 709.6) | 649.74 (443.5 to 1030.9) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours*nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=14,0,0,0 | 117.25 (71.2 to 274.6) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours*nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: AUC(0-24) of GSK3206944 | 16.44 (15.2 to 17.7) | 28.27 (25.0 to 31.6) | 106.55 (65.4 to 143.0) | 209.96 (172.2 to 368.7) | 374.49 (278.6 to 406.3) | 452.66 (377.9 to 692.4) | 586.70 (407.2 to 1019.2) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours*nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=14,0,0,0 | 115.31 (68.8 to 272.2) | — | — | — |
| Day 14, n=2,0,0,0 | 106.19 (94.7 to 117.7) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: Cmax of GSK3206944 | 3.28 (2.1 to 4.9) | 6.03 (4.8 to 7.3) | 19.39 (7.6 to 30.5) | 50.13 (27.5 to 82.3) | 71.67 (44.3 to 105.1) | 102.09 (51.5 to 206.0) | 121.22 (88.3 to 231.7) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=14,0,0,0 | 23.02 (11.3 to 56.8) | — | — | — |
| Day 14, n=2,0,0,0 | 15.34 (14.7 to 15.9) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: Tmax of GSK3206944 | 1.00 (1.0 to 2.0) | 2.00 (1.0 to 2.0) | 2.00 (1.0 to 2.0) | 2.01 (1.0 to 2.1) | 2.00 (2.0 to 4.0) | 2.00 (1.0 to 2.0) | 2.00 (1.0 to 2.0) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=14,0,0,0 | 2.00 (1.0 to 2.0) | — | — | — |
| Day 14, n=2,0,0,0 | 0.99 (0.98 to 1.0) | — | — | — |
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Part A: t1/2 of GSK3206944 | 4.97 (2.8 to 7.1) | 4.91 (4.8 to 5.0) | 4.10 (3.0 to 14.5) | 3.80 (3.5 to 4.3) | 7.81 (3.8 to 11.6) | 6.98 (4.1 to 8.8) | 6.76 (3.0 to 15.2) |
Blood samples were planned to be collected at indicated time points for pharmacokinetic analysis of GSK3206944. GSK3206944 is a metabolite of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3206944. PK parameters were calculated using standard non-compartmental analysis. GSK3206944 is a metabolite of GSK3358699.
| Hours | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1, n=14,0,0,0 | 5.02 (3.3 to 5.6) | — | — | — |
| Day 14, n=2,0,0,0 | 6.15 (5.5 to 6.8) | — | — | — |
Blood samples were collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes. GSK3206944 is a metabolite of GSK3358699.
| Nanogram per milliliter | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|
| Day 1: 1 hour | NA (NA to NA) | NA (NA to NA) | 0.177 (0.00 to 0.60) | 0.673 (0.00 to 1.08) | NA (NA to NA) | 1.243 (0.63 to 2.13) | 1.410 (0.94 to 1.94) |
| Day 1: 4 hours | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | 0.105 (0.00 to 0.26) | 0.149 (0.00 to 0.84) | 0.277 (0.00 to 0.38) | 0.297 (0.00 to 0.45) |
| Day 1: 8 hours | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
| Day 1: 24 hours | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
| Day 1: 48 hours | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
Blood samples were planned to be collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes. GSK3206944 is a metabolite of GSK3358699.
No measurements were reported for this outcome.
Blood samples were collected into sodium heparin tubes for the isolation of monocytes and for measurement of GSK3206944 concentrations in monocytes. GSK3206944 is a metabolite of GSK3358699.
| Nanogram per milliliter | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 RD | Part C: Cohort 7- GSK3358699 RD | Part C: Cohort 8- GSK3358699 RD |
|---|---|---|---|---|
| Day 1: 1 hour,n=14,0,0,0 | 0.313 (0.00 to 0.56) | — | — | — |
| Day 1: 4 hours,n=14,0,0,0 | NA (NA to NA) | — | — | — |
| Day 1: 8 hours,n=14,0,0,0 | NA (NA to NA) | — | — | — |
| Day 4: Pre-dose,n=14,0,0,0 | NA (NA to NA) | — | — | — |
| Day 8: Pre-dose,n=14,0,0,0 | NA (NA to NA) | — | — | — |
| Day 12: Pre-dose,n=14,0,0,0 | NA (NA to NA) | — | — | — |
| Day 13: 1 hour,n=1,0,0,0 | 0.317 (NA to NA) | — | — | — |
| Day 13: 4 hours,n=1,0,0,0 | NA (NA to NA) | — | — | — |
| Day 13: 8 hours,n=1,0,0,0 | NA (NA to NA) | — | — | — |
| Day 14: 1 hour,n=1,0,0,0 | 0.256 (NA to NA) | — | — | — |
| Day 14: 4 hours,n=1,0,0,0 | NA (NA to NA) | — | — | — |
| Day 14: 8 hours,n=1,0,0,0 | NA (NA to NA) | — | — | — |
| Day 14: 24 hours,n=1,0,0,0 | NA (NA to NA) | — | — | — |
| Day 14: 48 hours,n=1,0,0,0 | NA (NA to NA) | — | — | — |
Whole blood samples of 1 milliliter (mL) were collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL-6 and TNF alpha) were analyzed.
| Picogram per milliliter | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD |
|---|---|---|---|---|---|---|---|---|
| Day 1: IL6, 1 hour, n=17,5,3,6,6,0,6,6 | 10352.87 (6166.6 to 19166.3) | 15208.12 (7257.3 to 24940.9) | 20385.25 (13064.2 to 22017.3) | 12820.72 (9166.6 to 33445.0) | 15596.95 (3426.4 to 28751.1) | — | 10057.64 (5014.4 to 17359.8) | 5728.17 (4267.2 to 18422.7) |
| Day 1: IL6, 4 hours, n=17,5,3,6,6,0,6,6 | 13092.01 (4833.9 to 19117.2) | 13851.61 (9601.7 to 23110.3) | 19431.61 (16293.4 to 24387.6) | 15636.75 (8048.6 to 34008.3) | 12900.07 (6507.3 to 25108.1) | — | 12074.28 (4669.2 to 21515.6) | 7544.02 (5345.9 to 26788.0) |
| Day 1: IL6, 8 hours, n=17,5,3,6,6,0,6,6 | 12560.83 (7112.0 to 33941.2) | 13629.60 (10440.1 to 27946.6) | 28805.81 (24272.2 to 31362.4) | 16564.79 (11058.8 to 26785.4) | 17019.48 (12120.4 to 21106.7) | — | 16486.96 (7413.4 to 21952.6) | 8688.63 (6758.8 to 20765.0) |
| Day 1: IL6, 12 hour, n=17,5,3,6,6,0,6,6 | 15125.82 (2587.2 to 26028.6) | 13890.39 (11271.0 to 21279.4) | 28948.13 (24063.6 to 33176.4) | 18712.82 (6493.7 to 26803.1) | 15622.25 (10623.8 to 24243.3) | — | 12305.88 (8132.7 to 19539.9) | 6754.46 (3909.8 to 13207.0) |
| Day 1: IL6, 24 hours, n=17,5,3,6,6,0,6,6 | 12876.74 (5221.8 to 19587.8) | 16961.79 (10045.9 to 23511.8) | 23634.22 (17018.1 to 32159.5) | 14387.39 (9362.7 to 32140.8) | 12593.53 (8519.9 to 32945.4) | — | 12894.02 (5914.3 to 17523.1) | 8705.59 (6150.6 to 23530.0) |
| Day 1: IL6, 48 hours, n=17,5,3,6,6,0,6,6 | 13204.84 (6897.8 to 24379.3) | 16209.14 (8492.7 to 25387.3) | 27160.99 (17882.7 to 45604.5) | 14786.71 (10321.9 to 33336.3) | 13685.44 (7729.6 to 20697.6) | — | 14374.44 (8079.6 to 19835.0) | 8359.81 (6088.1 to 19757.4) |
| Day 1: MCP-1, 1 hour, n=17,5,2,6,6,0,6,6 | 2107.38 (692.3 to 4748.1) | 2997.62 (775.1 to 5062.0) | 2539.15 (1560.9 to 3517.4) | 1273.19 (872.5 to 2047.4) | 1278.42 (640.5 to 2640.6) | — | 1604.85 (863.0 to 3331.4) | 1047.32 (716.5 to 1933.0) |
| Day 1: MCP-1, 4 hours, n=17,5,3,6,6,0,6,6 | 1748.71 (878.2 to 3917.7) | 2638.95 (1272.7 to 2942.2) | 3774.02 (2841.1 to 4578.7) | 1410.01 (617.5 to 1973.0) | 1648.51 (559.9 to 4038.0) | — | 2604.00 (918.1 to 3465.2) | 1643.37 (1067.0 to 3385.4) |
| Day 1: MCP-1, 8 hours, n=17,5,3,6,6,0,6,6 | 1300.34 (713.0 to 3074.7) | 2911.87 (1297.8 to 4926.4) | 3145.66 (2964.7 to 3966.5) | 1606.85 (993.1 to 2784.3) | 1533.33 (634.0 to 3454.9) | — | 2312.12 (899.7 to 3203.8) | 1863.25 (1295.9 to 3392.0) |
| Day 1: MCP-1, 12 hour, n=17,5,3,6,6,0,6,6 | 1791.07 (808.9 to 4505.9) | 2738.20 (2017.5 to 4140.2) | 3048.56 (3045.4 to 4036.5) | 2003.41 (832.7 to 4276.2) | 1297.53 (903.3 to 5483.9) | — | 2062.41 (1546.5 to 3811.4) | 2270.49 (882.1 to 7042.9) |
| Day 1: MCP-1, 24 hours, n=17,5,3,6,6,0,6,6 | 1662.28 (673.9 to 3360.2) | 2349.62 (912.1 to 3608.3) | 2216.41 (1124.8 to 5178.2) | 1691.59 (661.1 to 2299.7) | 1062.86 (369.0 to 5821.6) | — | 2275.17 (845.9 to 2731.8) | 1988.64 (1360.9 to 3313.2) |
| Day 1: MCP-1, 48 hours, n=17,5,3,6,6,0,6,6 | 1398.36 (526.2 to 4408.1) | 2306.83 (577.0 to 4174.3) | 1621.46 (1505.3 to 3215.7) | 1729.87 (958.5 to 2877.5) | 1200.15 (514.4 to 3554.8) | — | 1595.51 (1082.1 to 2315.4) | 1828.23 (894.9 to 2434.1) |
| Day 1: TNF alpha, 1 hour, n=17,5,3,6,6,0,6,6 | 2525.78 (1073.6 to 4950.0) | 2281.20 (2214.6 to 5283.6) | 4340.00 (2395.2 to 6512.0) | 3455.53 (2172.3 to 12708.3) | 3916.76 (567.9 to 5873.5) | — | 1971.77 (992.6 to 3554.9) | 1552.10 (640.6 to 5120.6) |
| Day 1: TNF alpha, 4 hours, n=17,5,3,6,6,0,6,6 | 3189.81 (1264.1 to 5492.9) | 3452.27 (3139.9 to 8159.2) | 3381.52 (3014.8 to 8775.2) | 4493.55 (1481.7 to 16761.7) | 2672.58 (1527.3 to 7834.4) | — | 3618.72 (698.0 to 5482.5) | 1876.55 (1429.5 to 10939.6) |
| Day 1: TNF alpha, 8 hours, n=17,5,3,6,6,0,6,6 | 3673.78 (1891.2 to 8758.2) | 3630.47 (2520.6 to 8206.4) | 9631.19 (8462.1 to 9881.2) | 4612.79 (2513.7 to 10996.7) | 4908.42 (3867.7 to 7647.1) | — | 5233.22 (1875.8 to 6062.3) | 2934.21 (2142.3 to 8128.1) |
| Day 1: TNF alpha, 12 hour, n=17,5,3,6,6,0,6,6 | 4206.18 (717.0 to 9209.7) | 3680.34 (3268.1 to 6257.6) | 8736.93 (7805.2 to 10949.6) | 5139.53 (1199.2 to 10251.4) | 3079.37 (2178.8 to 7014.1) | — | 2846.57 (1964.6 to 7505.2) | 1729.42 (1203.4 to 2845.9) |
| Day 1: TNF alpha, 24 hours, n=17,5,3,5,6,0,6,6 | 3164.79 (845.9 to 6087.5) | 4528.14 (3348.7 to 7098.2) | 4694.58 (3321.5 to 13261.4) | 5576.01 (1699.4 to 12223.1) | 3543.62 (2185.0 to 9815.1) | — | 3649.08 (1319.2 to 4891.2) | 2741.96 (1683.3 to 8477.3) |
| Day 1: TNF alpha, 48 hours, n=17,5,3,6,6,0,6,6 | 3445.95 (2189.6 to 7880.2) | 4077.77 (2120.7 to 6772.6) | 10364.95 (3942.4 to 14023.2) | 4186.10 (2069.1 to 12454.5) | 3963.40 (1613.3 to 5663.8) | — | 3788.04 (2727.4 to 5746.1) | 2404.11 (1734.5 to 6985.8) |
Whole blood samples were planned to be collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL6 and TNF alpha) were planned to be analyzed.
No measurements were reported for this outcome.
Whole blood samples of 1 mL were collected in TruCulture tubes, containing LPS and incubated for 24 hours, post which the inflammatory mediators (MCP-1, IL-6 and TNF alpha) were analyzed.
| Picogram per milliliter | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|
| IL6:Day 1,1 hour,n=11,13,0,0,0 | 9488.65 (331.7 to 16540.5) | 9629.75 (3513.3 to 14975.4) | — | — | — |
| IL6:Day 1,4 hours,n=11,14,0,0,0 | 9121.35 (3866.4 to 18996.3) | 10686.75 (3976.0 to 17276.8) | — | — | — |
| IL6:Day 1,8 hours,n=11,14,0,0,0 | 13079.21 (5597.2 to 20424.0) | 15475.58 (1340.7 to 35210.3) | — | — | — |
| IL6:Day 2,Pre-dose,n=11,14,0,0,0 | 9323.67 (4126.4 to 19011.4) | 12396.71 (5456.9 to 19819.0) | — | — | — |
| IL6:Day 4,Pre-dose,n=11,14,0,0,0 | 11002.47 (2713.4 to 19232.1) | 12558.78 (4188.7 to 20344.2) | — | — | — |
| IL6:Day 8,Pre-dose,n=6,7,0,0,0 | 11305.84 (8590.8 to 31436.0) | 10766.02 (4511.8 to 13171.8) | — | — | — |
| IL6:Day 12,Pre-dose,n=5,4,0,0,0 | 9329.36 (7777.5 to 16845.5) | 10539.82 (7378.2 to 12671.6) | — | — | — |
| IL6:Day 13,Pre-dose,n=1,1,0,0,0 | 9966.64 (NA to NA) | 12743.26 (NA to NA) | — | — | — |
| IL6:Day 13,1 hour,n=1,1,0,0,0 | 11718.40 (NA to NA) | 12508.94 (NA to NA) | — | — | — |
| IL6:Day 13,4 hours,n=1,1,0,0,0 | 7099.42 (NA to NA) | 11616.53 (NA to NA) | — | — | — |
| IL6:Day 13,8 hours,n=1,1,0,0,0 | 10722.24 (NA to NA) | 16723.58 (NA to NA) | — | — | — |
| IL6:Day 14,Pre-dose,n=1,1,0,0,0 | 8918.96 (NA to NA) | 14654.83 (NA to NA) | — | — | — |
| IL6:Day 14,Pre LPS challenge,n=1,1,0,0,0 | 8696.65 (NA to NA) | 11340.79 (NA to NA) | — | — | — |
| IL6:Day 14,1 hour,n=1,1,0,0,0 | 10082.23 (NA to NA) | 13244.20 (NA to NA) | — | — | — |
| IL6:Day 14,4 hours,n=1,1,0,0,0 | 9122.21 (NA to NA) | 11543.08 (NA to NA) | — | — | — |
| IL6:Day 14,8 hours,n=1,1,0,0,0 | 10986.16 (NA to NA) | 12544.55 (NA to NA) | — | — | — |
| IL6:Day 14,24 hours,n=1,1,0,0,0 | 9176.89 (NA to NA) | 9114.15 (NA to NA) | — | — | — |
| IL6:Day 14,48 hours,n=1,1,0,0,0 | 8257.88 (NA to NA) | 10304.01 (NA to NA) | — | — | — |
| MCP-1:Day 1,1 hour,n=11,14,0,0,0 | 1739.49 (114.6 to 4212.9) | 2216.06 (1080.4 to 4084.7) | — | — | — |
| MCP-1:Day 1,4 hours,n=11,14,0,0,0 | 1825.09 (813.5 to 3719.8) | 2405.11 (996.0 to 5337.9) | — | — | — |
| MCP-1:Day 1,8 hours,n=11,14,0,0,0 | 2002.44 (656.7 to 4982.8) | 2044.64 (148.3 to 2887.4) | — | — | — |
| MCP-1:Day 2,Pre-dose,n=11,14,0,0,0 | 1939.09 (511.6 to 4614.3) | 1928.51 (818.2 to 4090.7) | — | — | — |
| MCP-1:Day 4,Pre-dose,n=11,14,0,0,0 | 1677.88 (537.9 to 3500.9) | 1939.65 (747.5 to 3428.4) | — | — | — |
| MCP-1:Day 8,Pre-dose,n=6,7,0,0,0 | 1638.33 (1129.3 to 6091.9) | 1719.26 (1336.5 to 3634.5) | — | — | — |
| MCP-1:Day 12,Pre-dose,n=5,4,0,0,0 | 1799.12 (1262.3 to 4483.2) | 2176.12 (497.9 to 2954.5) | — | — | — |
| MCP-1:Day 13,Pre-dose,n=1,1,0,0,0 | 1839.00 (NA to NA) | 513.36 (NA to NA) | — | — | — |
| MCP-1:Day 13,1 hour,n=1,1,0,0,0 | 2113.92 (NA to NA) | 294.72 (NA to NA) | — | — | — |
| MCP-1:Day 13,4 hours,n=1,1,0,0,0 | 1872.12 (NA to NA) | 890.77 (NA to NA) | — | — | — |
| MCP-1:Day 13,8 hours,n=1,1,0,0,0 | 1997.87 (NA to NA) | 1412.52 (NA to NA) | — | — | — |
| MCP-1:Day 14,Pre-dose,n=1,1,0,0,0 | 2007.09 (NA to NA) | 4935.03 (NA to NA) | — | — | — |
| MCP-1:Day 14,Pre LPS challenge,n=1,1,0,0,0 | 1876.05 (NA to NA) | 1981.15 (NA to NA) | — | — | — |
| MCP-1:Day 14,1 hour,n=1,1,0,0,0 | 3503.11 (NA to NA) | 3623.79 (NA to NA) | — | — | — |
| MCP-1:Day 14,4 hours,n=1,1,0,0,0 | 2066.72 (NA to NA) | 3293.92 (NA to NA) | — | — | — |
| MCP-1:Day 14,8 hours,n=1,1,0,0,0 | 2593.90 (NA to NA) | 3150.84 (NA to NA) | — | — | — |
| MCP-1:Day 14,24 hours,n=1,1,0,0,0 | 2082.28 (NA to NA) | 3372.94 (NA to NA) | — | — | — |
| MCP-1:Day 14,48 hours,n=1,1,0,0,0 | 1879.53 (NA to NA) | 2715.94 (NA to NA) | — | — | — |
| TNF alpha:Day 1,1 hour,n=11,13,0,0,0 | 1994.72 (135.2 to 3287.3) | 2078.66 (962.5 to 4069.3) | — | — | — |
| TNF alpha:Day 1,4 hours,n=11,14,0,0,0 | 1843.08 (596.4 to 4580.6) | 2297.36 (1173.8 to 4818.4) | — | — | — |
| TNF alpha:Day 1,8 hours,n=11,14,0,0,0 | 3692.36 (1094.9 to 6402.9) | 3854.86 (289.5 to 13254.5) | — | — | — |
| TNF alpha:Day 2,Pre-dose,n=11,14,0,0,0 | 2711.07 (849.2 to 4558.3) | 3028.33 (1506.6 to 5961.8) | — | — | — |
| TNF alpha:Day 4,Pre-dose,n=11,14,0,0,0 | 2987.24 (456.6 to 5033.0) | 3045.05 (1202.4 to 5443.8) | — | — | — |
| TNF alpha:Day 8,Pre-dose,n=6,7,0,0,0 | 2932.72 (2616.4 to 7598.9) | 2849.52 (784.2 to 3366.7) | — | — | — |
| TNF alpha:Day 12,Pre-dose,n=5,4,0,0,0 | 2482.03 (1958.2 to 3588.4) | 2407.60 (1143.7 to 2971.6) | — | — | — |
| TNF alpha:Day 13,Pre-dose,n=1,1,0,0,0 | 2311.66 (NA to NA) | 2995.36 (NA to NA) | — | — | — |
| TNF alpha:Day 13,1 hour,n=1,1,0,0,0 | 3495.21 (NA to NA) | 2648.27 (NA to NA) | — | — | — |
| TNF alpha:Day 13,4 hours,n=1,1,0,0,0 | 1573.18 (NA to NA) | 2815.39 (NA to NA) | — | — | — |
| TNF alpha:Day 13,8 hours,n=1,1,0,0,0 | 2486.89 (NA to NA) | 4472.25 (NA to NA) | — | — | — |
| TNF alpha:Day 14,Pre-dose,n=1,1,0,0,0 | 2304.40 (NA to NA) | 3327.69 (NA to NA) | — | — | — |
| TNF alpha:Day 14,Pre LPS challenge,n=1,1,0,0,0 | 2092.07 (NA to NA) | 2081.54 (NA to NA) | — | — | — |
| TNF alpha:Day 14,1 hour,n=1,1,0,0,0 | 2103.62 (NA to NA) | 3133.32 (NA to NA) | — | — | — |
| TNF alpha:Day 14,4 hours,n=1,1,0,0,0 | 1771.69 (NA to NA) | 2457.35 (NA to NA) | — | — | — |
| TNF alpha:Day 14,8 hours,n=1,1,0,0,0 | 2560.84 (NA to NA) | 3481.91 (NA to NA) | — | — | — |
| TNF alpha:Day 14,24 hours,n=1,1,0,0,0 | 1482.94 (NA to NA) | 2187.40 (NA to NA) | — | — | — |
| TNF alpha:Day 14,48 hours,n=1,1,0,0,0 | 1909.65 (NA to NA) | 2597.32 (NA to NA) | — | — | — |
Collected over Up to Day 193 in Part A and up to Day 49 in Part C (Cohorts 4 and 5). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part A: Placebo SD | 0/23 (0%) | 0/23 (0%) | 4/23 (17.4%) |
| Part A: GSK3358699 1 mg SD | 0/5 (0%) | 0/5 (0%) | 2/5 (40%) |
| Part A: GSK3358699 3 mg SD | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Part A: GSK3358699 10 mg SD | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) |
| Part A: GSK3358699 20 mg SD | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| Part A: GSK3358699 25 mg SD | 0/12 (0%) | 0/12 (0%) | 8/12 (66.7%) |
| Part A: GSK3358699 30 mg SD | 0/6 (0%) | 0/6 (0%) | 4/6 (66.7%) |
| Part A: GSK3358699 40 mg SD | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | — | — | — |
| Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | — | — | — |
| Part C: Cohort 4 and 5- Placebo RD | 0/11 (0%) | 0/11 (0%) | 7/11 (63.6%) |
| Part C: Cohort 4 and 5- GSK3358699 10 mg RD | 0/14 (0%) | 1/14 (7.1%) | 7/14 (50%) |
| Part C: Cohort 6- GSK3358699 or Placebo RD | — | — | — |
| Part C: Cohort 7- GSK3358699 or Placebo RD | — | — | — |
| Part C: Cohort 8- GSK3358699 or Placebo RD | — | — | — |
| Event | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Atrial fibrillationCardiac disorders | 0/23 | 0/5 | 0/3 | 0/6 | 0/6 | 0/12 | 0/6 | 0/6 | — | — | 0/11 | 1/14 | — | — | — |
| Event | Part A: Placebo SD | Part A: GSK3358699 1 mg SD | Part A: GSK3358699 3 mg SD | Part A: GSK3358699 10 mg SD | Part A: GSK3358699 20 mg SD | Part A: GSK3358699 25 mg SD | Part A: GSK3358699 30 mg SD | Part A: GSK3358699 40 mg SD | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HeadacheNervous system disorders | 2/23 | 1/5 | 1/3 | 1/6 | 2/6 | 4/12 | 1/6 | 2/6 | — | — | 2/11 | 2/14 | — | — | — |
| MalaiseGeneral disorders | 0/23 | 0/5 | 1/3 | 0/6 | 0/6 | 0/12 | 0/6 | 0/6 | — | — | 0/11 | 0/14 | — | — | — |
| PalpitationsCardiac disorders | 0/23 | 0/5 | 1/3 | 0/6 | 0/6 | 0/12 | 0/6 | 0/6 | — | — | 1/11 | 0/14 | — | — | — |
| DiarrhoeaGastrointestinal disorders | 0/23 | 0/5 | 1/3 | 0/6 | 0/6 | 0/12 | 0/6 | 0/6 | — | — | 0/11 | 0/14 | — | — | — |
| NauseaGastrointestinal disorders | 0/23 | 0/5 | 1/3 | 0/6 | 0/6 | 0/12 | 0/6 | 0/6 | — | — | 0/11 | 0/14 | — | — | — |
| RhinorrhoeaRespiratory, thoracic and mediastinal disorders | 0/23 | 0/5 | 1/3 | 1/6 | 0/6 | 0/12 | 0/6 | 0/6 | — | — | 0/11 | 0/14 | — | — | — |
| NeutropeniaBlood and lymphatic system disorders | 0/23 | 1/5 | 0/3 | 0/6 | 0/6 | 0/12 | 0/6 | 0/6 | — | — | 0/11 | 0/14 | — | — | — |
| HordeolumInfections and infestations | 0/23 | 0/5 | 0/3 | 0/6 | 0/6 | 0/12 | 0/6 | 1/6 | — | — | 0/11 | 0/14 | — | — | — |
| Feeling hotGeneral disorders | 0/23 | 0/5 | 0/3 | 0/6 | 0/6 | 2/12 | 0/6 | 0/6 | — | — | 0/11 | 0/14 | — | — | — |
| PyrexiaGeneral disorders | 1/23 | 0/5 | 0/3 | 0/6 | 0/6 | 0/12 | 1/6 | 0/6 | — | — | 0/11 | 0/14 | — | — | — |
This study was terminated due to strategic reasons following the emergence of new data. Part B and Part C (Cohorts 6 to 8) were not initiated due to termination of the study. Hence, no participants were enrolled in Part B and Part C (Cohorts 6 to 8).
| Age, Customized(Participants) | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | 0 | 0 | — | — | — | 1 |
| >18 and <65 years | 1 | 1 | 2 | 2 | 2 | 4 | 1 | 3 | 1 | 2 | 1 | 2 | — | — | 11 | 14 | — | — | — | 47 |
| >=65 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | 0 | 0 | — | — | — | 0 |
| Sex: Female, Male(Participants) | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | 0 | 0 | — | — | — | 0 |
| Male | 1 | 2 | 2 | 2 | 2 | 4 | 1 | 3 | 1 | 2 | 1 | 2 | — | — | 11 | 14 | — | — | — | 48 |
| Race/Ethnicity, Customized(Participants) | Part A: Cohort 1- Sequence PCEP | Part A: Cohort 1- Sequence PCER | Part A: Cohort 1- Sequence APEP | Part A: Cohort 1- Sequence APER | Part A: Cohort 1- Sequence ACPP | Part A: Cohort 1- Sequence ACPR | Part A: Cohort 2- Sequence PDFP | Part A: Cohort 2- Sequence PDFR | Part A: Cohort 2- Sequence BPFP | Part A: Cohort 2- Sequence BPFR | Part A: Cohort 2- Sequence BDPP | Part A: Cohort 2- Sequence BDPR | Part B: Cohort 3- GSK3358699 Fed + GSK3358699 Fasted | Part B: Cohort 3- GSK3358699 Fasted + GSK3358699 Fed | Part C: Cohort 4 and 5- Placebo RD | Part C: Cohort 4 and 5- GSK3358699 10 mg RD | Part C: Cohort 6- GSK3358699 or Placebo RD | Part C: Cohort 7- GSK3358699 or Placebo RD | Part C: Cohort 8- GSK3358699 or Placebo RD | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Black or African American | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | 1 | 0 | — | — | — | 2 |
| White-White/Caucasian/European Heritage | 1 | 2 | 2 | 2 | 2 | 3 | 1 | 3 | 1 | 2 | 1 | 1 | — | — | 10 | 14 | — | — | — | 45 |
| Multiple | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | — | — | 0 | 0 | — | — | — | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request site.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: IPD will be made available, within 6 months of publishing the results of the primary endpoints of the study.
Access criteria: Access is provided, after a research proposal is submitted and has submitted approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided, for an initial period of 12 months but an extension can be granted, when justified for up to another 12 months.
Data sharing details ↗ · clinicalstudydatarequest.com
Ran from Mar 2018 to primary completion in May 2019, 13 months.
Results were first posted in Dec 2020, 1 year 7 months after primary completion.
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Studies of the drugs tested here: Granulocyte-Macrophage Colony-Stimulating Factor · Lipopolysaccharides