A Phase 2 interventional study of Placebo ELLIPTA and Nemiralisib ELLIPTA 50 µg in Pulmonary Disease, Chronic Obstructive, sponsored by GlaxoSmithKline. Terminated at 162 sites in 16 countries. Open to participants aged 40 Years to 80 Years. Per ClinicalTrials.gov, last updated 2021-07-14.
Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment
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Among 276 studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline — 7 open to participants now, 8 under way, 5 of them phase 3. Pulmonary Disease, Chronic Obstructive · GlaxoSmithKline.
Among the 276 studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline, this one is the 24th largest by enrollment of the 236 interventional ones that give a count, is one of 18 that started in 2017, is one of 46 in phase 2, and was the 241st registered.
5,522 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 857 are open to participants now.
Browse Pulmonary Disease, Chronic Obstructive studies →7 of the 276 studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline are open now, in 12 countries. Recruiting first, the newest first:
GlaxoSmithKline · Sites in United States, Argentina
Ages 40–80
GlaxoSmithKline · Sites in United States, Japan
Ages 40–80
GlaxoSmithKline · Sites in United Kingdom
Ages 18–55 · Healthy volunteers
GlaxoSmithKline · Sites in United States, Australia, Bulgaria and 10 more countries
Ages 40–75
GlaxoSmithKline · Sites in United States, Argentina, Australia and 13 more countries
Ages 40–80
By country, each count listing its studies:
Of the 557 Pulmonary Disease, Chronic Obstructive studies recruiting now, 306 (55%) set no upper age limit and 82 (15%) stop at 75 or younger; 29 take children under 18; 89 take healthy volunteers.
This study: 40 Years to 80 Years · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
276 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 84 · Phase 2 47 · Phase 3 65 · Phase 4 38
First in 2000; this study’s year is marked. 18 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 943 is above the median of 62 across 3,840 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.
Median enrollment 101 across the 236 interventional studies, 1,248 across the 40 observational. Of the 264 that completed or were terminated, 141 (53%) have results posted.
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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.
2 of the studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06154837GlaxoSmithKlineA Study for GSK3862995B in Healthy Participants and Participants With Chronic Obstructive Pulmonary Disease | 2026-12-16 |
| NCT07789899GlaxoSmithKlineA Study to Evaluate Pharmacokinetics, Safety, and Tolerability of Two GSK3862995B Formulations in Healthy Participants | 2027-09-07 |
Add all 2 to your calendar (.ics) → With an account.
Among the 276 studies in Pulmonary Disease, Chronic Obstructive by GlaxoSmithKline, from their registry updates:
This tab as a report to print or save as PDF → With an account.
Nemiralisib is being developed as an anti-inflammatory drug for the treatment of inflammatory airways disease. This study is designed to assess the dose response, efficacy, safety, and pharmacokinetics of nemiralisib across a range of doses [up to 750 micrograms (µg)] compared with placebo. The study consists of a Screening Period, a 12-Week Treatment Period and a 12-Week Post-Treatment Follow-Up Period. Approximately 1,250 subjects with an acute moderate or severe exacerbation of COPD requiring standard of care (SoC) therapy will be randomized in this double-blind study. Subjects will be randomized to receive different doses of nemiralisib or placebo via ELLIPTA® inhaler. The total duration of study participation is approximately 6 months (170 days). ELLIPTA is the registered trademark of GlaxoSmithKline (GSK) group of companies.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
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.
Chronic obstructive pulmonary disease: long-term lung disease that makes it hard to breathe out, including emphysema and chronic bronchitis.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
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.
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.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
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.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
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.
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.
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.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
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.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
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.
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.
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.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
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.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
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.
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.
Eligible subjects will receive placebo ELLIPTA dry powder (blended with lactose) for oral inhalation once daily in the morning for 12 weeks. Albuterol (Salbutamol) MDI or nebules will also be provided to all subjects for use as rescue medication as needed.
Drug: Placebo ELLIPTA · Drug: Albuterol (Salbutamol) MDI or nebules · Drug: Standard of care therapy
Eligible subjects will receive nemiralisib ELLIPTA 50 µg dry powder (blended with lactose and magnesium stearate) for oral inhalation once daily in the morning for 12 weeks. Albuterol (Salbutamol) MDI or nebules will also be provided to all subjects for use as rescue medication as needed.
Drug: Nemiralisib ELLIPTA 50 µg · Drug: Albuterol (Salbutamol) MDI or nebules · Drug: Standard of care therapy
Eligible subjects will receive nemiralisib ELLIPTA 100 µg dry powder (blended with lactose and magnesium stearate) for oral inhalation once daily in the morning for 12 weeks. Albuterol (Salbutamol) MDI or nebules will also be provided to all subjects for use as rescue medication as needed.
Drug: Nemiralisib ELLIPTA 100 µg · Drug: Albuterol (Salbutamol) MDI or nebules · Drug: Standard of care therapy
Eligible subjects will receive nemiralisib ELLIPTA 250 µg dry powder (blended with lactose and magnesium stearate) for oral inhalation once daily in the morning for 12 weeks. Albuterol (Salbutamol) MDI or nebules will also be provided to all subjects for use as rescue medication as needed.
Drug: Nemiralisib ELLIPTA 250 µg · Drug: Albuterol (Salbutamol) MDI or nebules · Drug: Standard of care therapy
Eligible subjects will receive nemiralisib ELLIPTA 500 µg dry powder (blended with lactose and magnesium stearate) for oral inhalation once daily in the morning for 12 weeks. Albuterol (Salbutamol) MDI or nebules will also be provided to all subjects for use as rescue medication as needed.
Drug: Nemiralisib ELLIPTA 500 µg · Drug: Albuterol (Salbutamol) MDI or nebules · Drug: Standard of care therapy
Eligible subjects will receive nemiralisib ELLIPTA 750 µg dry powder (blended with lactose and magnesium stearate) for oral inhalation once daily in the morning for 12 weeks. Albuterol (Salbutamol) MDI or nebules will also be provided to all subjects for use as rescue medication as needed.
Drug: Nemiralisib ELLIPTA 750 µg · Drug: Albuterol (Salbutamol) MDI or nebules · Drug: Standard of care therapy
Placebo will be administered via oral inhalation route once daily in the morning.
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 50 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 100 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 250 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 500 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
Nemiralisib is a potent and highly selective inhaled PI3Kd inhibitor being developed as an anti-inflammatory for the treatment of inflammatory airways disease. Nemiralisib 750 µg will be administered as a dry powder inhaler via oral inhalation route. In addition, subjects will receive SOC therapy for the index acute moderate or severe exacerbation of COPD.
Albuterol (Salbutamol) MDI or nebules will be provided to all subjects as a rescue medication.
SoC therapy for the index exacerbation is defined as treatment with oral/systemic corticosteroid (prednisone 40 mg/day or equivalent) for 5 days and antibiotic for 7 days. Subjects will receive SoC as prescribed by the Investigator or medically qualified designee. The dose and/or duration of prednisone and/or the antibiotic can be modified according to the Investigator's/medically qualified designee's judgment or according to local country/institution practice.
Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator
FEV1 is maximal amount of air exhaled forcefully from lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered 4 inhalations of albuterol (salbutamol) via MDI using spacer/valved-holding chamber or via one nebulized treatment. Post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and post-bronchodilator. Change from Baseline in clinic visit trough FEV1 at Day 84 measured post-bronchodilator is FEV1 measured prior to dosing and post-bronchodilator on Day 84 minus post-bronchodilator Baseline FEV1. Bayesian repeated measure model adjusted for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender was used. Posterior adjusted median change from Baseline and 95% highest posterior density (HPD) credible interval (CrI) was presented.
Time frame: Baseline and Day 84
Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period
Moderate COPD exacerbations are defined as worsening symptoms of COPD treated with short-acting bronchodilators (SABDs) plus antibiotics and/or oral/systemic corticosteroids. Severe COPD exacerbations are defined as worsening symptoms of COPD that require hospitalization or visit to the emergency room. Severe exacerbation may also be associated with acute respiratory failure. Rate of exacerbations was analyzed using Bayesian Poisson model adjusting for length of on-treatment follow-up, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior median exacerbation rate and 95% HPD CrI has been presented.
Time frame: Up to Week 12
Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation
Number of participants with time to next (on-treatment) moderate/severe exacerbation following index exacerbation during the 12-Week Treatment Period was defined as time from the date of randomization until the date of onset of the first moderate/severe exacerbation whilst on study treatment. Participants who did not have an exacerbation whilst on study treatment were censored at the date of their last dose of study treatment. Time to next exacerbation was analyzed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.
Time frame: Up to Week 12
Change From Baseline in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator
Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from Baseline in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre-bronchodilator is defined as FEV1 measured prior to dosing and pre-bronchodilator on Days 14, 28, 56 and 84 minus pre-bronchodilator Baseline FEV1.
Time frame: Baseline and Days 14, 28, 56 (pre and post bronchodilaor), 84 (pre-bronchodilator) and at hospital discharge (maximum 24 Weeks)
Change From Hospital Discharge in Clinic Visit Trough FEV1 Measured Pre and Post-bronchodilator
Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10 to 30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is defined as latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from hospital discharge in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre- and post-bronchodilator is defined as FEV1 measured prior to dosing and pre- and post-bronchodilator on Days 14, 28, 56 and 84 minus pre and post-bronchodilator Baseline FEV1.
Time frame: Baseline and pre- and post-bronchodilator on Days 14, 28, 56 and 84
Percentage of Participants Achieving the Exacerbations of Chronic Pulmonary Disease Tool (EXACT) Definition of Recovery From the Index Exacerbation
EXACT patient-reported outcome (EXACT-PRO), 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an electronic diary (eDiary). Total score ranges from 0-100, higher score indicates more severe condition. Participants were required to complete EXACT-PRO every evening; however, on the day of randomization it was to be completed in the morning. Response was decrease in rolling average EXACT Total Score \>=9 points from maximum observed value, sustained for \>=7 days, with first of 7 days defined as recovery day. Analysis was performed using Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender.
Time frame: Days 14, 28, 56 and 84
Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool
Time to EXACT-defined recovery from index exacerbation is defined as time from the date of randomization until date of the first EXACT-defined recovery day during the 12-Week Treatment Period. EXACT-defined recovery from the index exacerbation is defined as a decrease in the Rolling Average EXACT total Score \>=9 points from the Maximum Observed Value, sustained for \>=7 days, with the first of the 7 days defined as the recovery day. Analysis was performed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Number of participants reporting events is presented.
Time frame: From randomization to Week 12
Mean Severity of Subsequent Health Care Resource Use (HCRU) Exacerbations Defined by EXACT
Severity of subsequent HCRU-defined exacerbations defined by EXACT was defined as the highest EXACT Total Score (not using the 3-day Rolling Average) during the period from date of onset of the subsequent HCRU-exacerbation until date of EXACT-defined recovery of subsequent exacerbation. EXACT-PRO, 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an eDiary. Total score ranges from 0-100, higher score indicates more severe condition. For participants with more than one subsequent exacerbation, severity was calculated for each subsequent exacerbation.
Time frame: Up to Week 12
Percentage of Responders Using the COPD Assessment Test (CAT) on Treatment Days 28, 56, and 84, and Following EXACT Defined Recovery From the Index Exacerbation
The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating severe condition. The percentage of responders using the CAT is defined as number of participants with a decrease from Baseline in CAT Total Score \>=2 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Percentage of responders using CAT was derived only for participants with a Baseline CAT Total Score \>=2. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.
Time frame: Days 28, 56 and 84
Change From Baseline in CAT Total Score
The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score was calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating more severe condition. Baseline (Day 1) is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in CAT Total Score is defined as CAT Total Score on Days 28, 56 and 84 minus Baseline CAT Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI has been presented.
Time frame: Baseline and at Days 28, 56 and 84
Percentage of Responders on the St. George's Respiratory Questionnaire (SGRQ) Total Score as Measured by the SGRQ for COPD Participants (SGRQ-C) at Days 28, 56, and 84
SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to the SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. The percentage of responders on the SGRQ Total Score was derived for participants with a Baseline SGRQ Total Score \>=4. Percentage of responders on the SGRQ Total Score is defined as number of participants with a decrease from Baseline in SGRQ Total Score \>=4 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.
Time frame: Days 28, 56 and 84
Change From Baseline in SGRQ Total Score at Days 28, 56 and 84
SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. Scores on a scale were calculated as 100 multiplied by summed weights from positive items in questionnaire divided by sum of weights of all items in questionnaire. Baseline (Day 1) is defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in SGRQ Total Score is defined as SGRQ Total Score on Days 28, 56 and 84 minus Baseline SGRQ Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI was presented
Time frame: Baseline and Days 28, 56 and 84
Mean Number of Occasions of Rescue Medication Use Per Day
Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Rescue medication use was recorded as the number of occasions of rescue medication use each day. The mean number of occasions of rescue medication use per day is defined as sum of the number of occasions of rescue medication use each day within the time-period divided by the total number of days with non-missing values within the time-period. Over the 12-Week treatment period is defined as Day 1 to Day of last dose.
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period
Percentage of Rescue-free Days
Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Percentage of Rescue-Free Days is defined as sum of the number of days where the number of occasions of rescue medication use is zero within the time-period divided by total number of days with non-missing values within the time-period multiplied by 100 where the time-period is defined as follows: Week 1: Day 1-7; Week 2: Day 8 - 14; Week 3: Day 15-21; Week 4: Day 22-28; Week 5: Day 29-35; Week 6: Day 36-42; Week 7: Day 43-49; Week 8: Day 50-56; Week 9: Day 57-63; Week 10: Day 64-70; Week 11: Day 71-77; Week 12: Day 78 to Day of last dose; Over the 12-Week: Day 1 to Day of last dose.
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 of treatment and over the Week 12 treatment period
Plasma Concentration of Nemiralisib
Plasma samples were collected at indicated time points and analyzed for concentrations of Nemiralisb. Pharmacokinetic (PK) Population consists of all participants in the Safety population who had at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values will be considered as non-missing values). Participants were summarized according to the treatment that they actually received.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Number of Participants Reporting Non-serious Adverse Events (Non-SAEs), SAEs and AE of Special Interest (AESI)
An AE is any untoward medical occurrence in a clinical investigation subject, 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, is a congenital anomaly/ birth effect and other important medical events. Safety Population consists of all randomized participants who received at least one dose of study treatment. Participants were summarized according to treatment that they actually received.
Time frame: Up to Week 24
Number of Participants With Worst Case Post Baseline Diastolic Blood Pressure (DBP), Systolic Blood Pressure (SBP) and Pulse Rate
The DBP, SBP and pulse rate were measured with participants seated at least 5 minutes before the assessments. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.
Time frame: Up to Week 16
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
A single 12-lead ECG with a 15-second rhythm strip was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Abnormal ECG findings are presented.
Time frame: Screening, Days 14, 84, 112 and at early withdrawal
Number of Participants With Worst Case Post Baseline Clinical Chemistry Values
Blood samples were collected for the analysis of clinical chemistry parameters including: blood urea nitrogen (BUN), creatinine (Crt), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin, total protein and albumin (Alb). Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.
Time frame: Upto Week 16
Number of Participants With Worst Case Post Baseline Hematology Values
Blood samples were collected for the analysis of hematology parameters including: platelets (Pla), red blood cells count, Hemoglobin (Hb), Hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), percentage reticulocytes, neutrophils (Neu), lymphocytes (Lym), monocytes, eosinophils, leukocytes (Leu) and basophils. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.
Time frame: Upto Week 16
Number of Participants Reporting COPD Exacerbations
Participants reporting acute COPD exacerbations during the study period has been presented.
Time frame: Up to Week 16
Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Time to Reach Cmax (Tmax) of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib
Plasma samples were collected at indicated time points and analyzed.
Time frame: Pre-dose, 0-1 hour, >1-6 hours post-dose on Days 14 and 28
This was a Phase IIb, multicenter, randomized, stratified, double-blind (sponsor open), placebo controlled parallel-group study in participants who presented with an acute moderate or severe exacerbation of chronic obstructive pulmonary disease (COPD) requiring Standard of Care (SoC).
| Milestone | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Started | 276 | 22 | 91 | 92 | 90 | 89 | 278 |
| Completed | 244 | 19 | 79 | 81 | 75 | 73 | 233 |
| Not completed | 32 | 3 | 12 | 11 | 15 | 16 | 45 |
| Withdrew: Withdrawal by subject | 11 | 1 | 5 | 6 | 3 | 6 | 16 |
| Withdrew: Physician decision | 3 | 1 | 0 | 0 | 1 | 2 | 3 |
| Withdrew: Lost to follow-up | 2 | 0 | 1 | 0 | 1 | 2 | 3 |
| Withdrew: Protocol-defined stopping criteria | 9 | 0 | 0 | 0 | 2 | 1 | 1 |
| Withdrew: Protocol violation | 2 | 0 | 0 | 0 | 1 | 0 | 3 |
| Withdrew: Lack of efficacy | 1 | 1 | 1 | 1 | 1 | 0 | 3 |
| Withdrew: Adverse event | 4 | 0 | 5 | 4 | 6 | 5 | 16 |
FEV1 is maximal amount of air exhaled forcefully from lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered 4 inhalations of albuterol (salbutamol) via MDI using spacer/valved-holding chamber or via one nebulized treatment. Post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and post-bronchodilator. Change from Baseline in clinic visit trough FEV1 at Day 84 measured post-bronchodilator is FEV1 measured prior to dosing and post-bronchodilator on Day 84 minus post-bronchodilator Baseline FEV1. Bayesian repeated measure model adjusted for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender was used. Posterior adjusted median change from Baseline and 95% highest posterior density (HPD) credible interval (CrI) was presented.
| Liters | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Change From Baseline in Clinic Visit Trough Forced Expiratory Volume in One Second (FEV1) at Day 84 Measured Post Bronchodilator | 0.052 (0.018 to 0.091) | 0.031 (-0.090 to 0.149) | 0.026 (-0.036 to 0.084) | 0.014 (-0.044 to 0.073) | 0.058 (-0.002 to 0.118) | 0.049 (-0.017 to 0.113) | 0.049 (0.012 to 0.086) |
Moderate COPD exacerbations are defined as worsening symptoms of COPD treated with short-acting bronchodilators (SABDs) plus antibiotics and/or oral/systemic corticosteroids. Severe COPD exacerbations are defined as worsening symptoms of COPD that require hospitalization or visit to the emergency room. Severe exacerbation may also be associated with acute respiratory failure. Rate of exacerbations was analyzed using Bayesian Poisson model adjusting for length of on-treatment follow-up, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior median exacerbation rate and 95% HPD CrI has been presented.
| No.of exacerbation per 84 Days | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Rate of Moderate and Severe Exacerbations Over 12-week Treatment Period | 0.31 (0.25 to 0.39) | NA (NA to NA) | 0.29 (0.20 to 0.39) | 0.28 (0.20 to 0.38) | 0.32 (0.23 to 0.43) | 0.20 (0.13 to 0.29) | 0.36 (0.29 to 0.43) |
Number of participants with time to next (on-treatment) moderate/severe exacerbation following index exacerbation during the 12-Week Treatment Period was defined as time from the date of randomization until the date of onset of the first moderate/severe exacerbation whilst on study treatment. Participants who did not have an exacerbation whilst on study treatment were censored at the date of their last dose of study treatment. Time to next exacerbation was analyzed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.
| Participants | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Number of Participants With Time to Next Moderate/Severe Exacerbation Following Index Exacerbation | 72 | 3 | 24 | 25 | 26 | 15 | 80 |
Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10-30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from Baseline in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre-bronchodilator is defined as FEV1 measured prior to dosing and pre-bronchodilator on Days 14, 28, 56 and 84 minus pre-bronchodilator Baseline FEV1.
| Liters | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Day 14, Pre, n=240, 20, 85, 83, 76, 76, 238 | 0.008 ± 0.2729 | 0.100 ± 0.2511 | -0.021 ± 0.2657 | -0.013 ± 0.2509 | 0.053 ± 0.2958 | 0.041 ± 0.2738 | 0.023 ± 0.2561 |
| Day 14, Post, n=248, 20, 86, 83, 77, 78, 241 | 0.034 ± 0.2707 | 0.075 ± 0.2425 | 0.010 ± 0.2168 | -0.050 ± 0.2477 | 0.054 ± 0.2983 | 0.073 ± 0.2655 | 0.044 ± 0.2216 |
| Day 28, Pre, n=239, 20, 82, 79, 75, 71, 232 | 0.017 ± 0.2585 | 0.081 ± 0.2661 | -0.034 ± 0.2875 | -0.010 ± 0.2333 | 0.064 ± 0.2592 | 0.016 ± 0.2713 | 0.020 ± 0.2512 |
| Day 28, Post, n=245, 19, 83, 81, 76, 72, 232 | 0.036 ± 0.2647 | 0.059 ± 0.2575 | 0.004 ± 0.2183 | -0.034 ± 0.2401 | 0.049 ± 0.2639 | 0.027 ± 0.2369 | 0.029 ± 0.2307 |
| Day 56, Pre, n=230, 20, 78, 76, 73, 67, 224 | 0.005 ± 0.2295 | -0.006 ± 0.2636 | -0.024 ± 0.3210 | 0.011 ± 0.2415 | 0.022 ± 0.2522 | -0.004 ± 0.2233 | -0.001 ± 0.2858 |
| Day 56, Post, n=237, 19, 78, 77, 74, 69, 224 | 0.020 ± 0.2614 | -0.002 ± 0.2252 | -0.012 ± 0.2524 | 0.004 ± 0.2373 | 0.026 ± 0.2556 | -0.011 ± 0.2260 | 0.011 ± 0.2470 |
| Day 84, Pre, n=210, 17, 71, 73, 66, 58, 212 | 0.000 ± 0.2566 | 0.003 ± 0.2232 | -0.049 ± 0.2549 | 0.005 ± 0.2668 | 0.015 ± 0.2739 | 0.007 ± 0.2461 | 0.010 ± 0.2829 |
| Hospital discharge, Pre, n=23, 2, 8, 8, 7, 3, 22 | 0.071 ± 0.1586 | 0.168 ± 0.2652 | 0.108 ± 0.3888 | 0.056 ± 0.1782 | 0.052 ± 0.3481 | 0.162 ± 0.1426 | 0.075 ± 0.1974 |
| Hospital discharge, Post, n=8, 2, 1, 1, 1, 0, 6 | 0.134 ± 0.1514 | 0.153 ± 0.0933 | 0.083 ± NA | -0.076 ± NA | 0.094 ± NA | — | -0.006 ± 0.1079 |
Pulmonary function was measured by FEV1, defined as maximal amount of air exhaled forcefully from the lungs in 1 second. Post-bronchodilator FEV1 was conducted approximately 10 to 30 minutes after participant was administered with 4 inhalations of albuterol via MDI using a spacer/valved-holding chamber or via 1 nebulized treatment. Pre-bronchodilator and post-bronchodilator Baseline FEV1 is defined as latest FEV1 measured prior to first dose of study treatment and pre-bronchodilator and post-bronchodilator, respectively. Change from hospital discharge in clinic visit trough FEV1 at Days 14, 28, 56 and 84 measured pre- and post-bronchodilator is defined as FEV1 measured prior to dosing and pre- and post-bronchodilator on Days 14, 28, 56 and 84 minus pre and post-bronchodilator Baseline FEV1.
| Liters | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Day 14, Pre, n=20, 2, 8, 8, 6, 4, 20 | 0.082 ± 0.2783 | 0.355 ± 0.4207 | 0.069 ± 0.3012 | -0.049 ± 0.1882 | -0.069 ± 0.4905 | 0.173 ± 0.5137 | 0.002 ± 0.2343 |
| Day 14, Post, n=5, 2, 1, 1, 1, 0, 5 | 0.056 ± 0.3372 | 0.431 ± 0.5190 | 0.119 ± NA | 0.310 ± NA | -0.305 ± NA | — | -0.021 ± 0.1326 |
| Day 28, Pre, n=37, 2, 14, 8, 10, 9, 37 | 0.026 ± 0.2691 | 0.261 ± 0.5204 | 0.012 ± 0.2910 | -0.085 ± 0.2072 | 0.012 ± 0.4020 | 0.030 ± 0.4029 | -0.046 ± 0.2639 |
| Day 28, Post, n=22, 2, 8, 1, 4, 4, 22 | 0.034 ± 0.2779 | 0.334 ± 0.5614 | 0.130 ± 0.2327 | 0.130 ± NA | 0.009 ± 0.2006 | 0.007 ± 0.3237 | -0.094 ± 0.2293 |
| Day 56, Pre, n=37, 2, 14, 8, 9, 10, 36 | 0.019 ± 0.2282 | 0.106 ± 0.6138 | 0.019 ± 0.3509 | 0.014 ± 0.1938 | -0.074 ± 0.3847 | -0.042 ± 0.1840 | -0.054 ± 0.2942 |
| Day 56, Post, n=22, 2, 7, 1, 4, 5, 21 | -0.014 ± 0.2896 | 0.139 ± 0.6838 | 0.042 ± 0.3068 | 0.098 ± NA | -0.056 ± 0.3572 | -0.072 ± 0.1490 | -0.135 ± 0.2410 |
| Day 84, Pre, n=37, 2, 12, 8, 7, 10, 35 | 0.007 ± 0.2741 | -0.027 ± 0.4554 | 0.121 ± 0.2770 | -0.081 ± 0.1738 | -0.072 ± 0.4391 | 0.043 ± 0.2511 | -0.062 ± 0.2816 |
| Day 84, Post, n=22, 2, 6, 1, 4, 5, 22 | -0.039 ± 0.2610 | 0.133 ± 0.5162 | 0.037 ± 0.3341 | 0.108 ± NA | 0.021 ± 0.3151 | 0.006 ± 0.2180 | -0.106 ± 0.2956 |
EXACT patient-reported outcome (EXACT-PRO), 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an electronic diary (eDiary). Total score ranges from 0-100, higher score indicates more severe condition. Participants were required to complete EXACT-PRO every evening; however, on the day of randomization it was to be completed in the morning. Response was decrease in rolling average EXACT Total Score \>=9 points from maximum observed value, sustained for \>=7 days, with first of 7 days defined as recovery day. Analysis was performed using Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender.
| Percentage of participants | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Day 14 | 29 | 27 | 37 | 29 | 28 | 24 | 32 |
| Day 28 | 40 | 41 | 52 | 43 | 42 | 27 | 42 |
| Day 56 | 49 | 45 | 59 | 52 | 50 | 31 | 50 |
| Day 84 | 51 | 50 | 59 | 54 | 50 | 37 | 54 |
Time to EXACT-defined recovery from index exacerbation is defined as time from the date of randomization until date of the first EXACT-defined recovery day during the 12-Week Treatment Period. EXACT-defined recovery from the index exacerbation is defined as a decrease in the Rolling Average EXACT total Score \>=9 points from the Maximum Observed Value, sustained for \>=7 days, with the first of the 7 days defined as the recovery day. Analysis was performed using a Bayesian Cox proportional hazards model adjusting for treatment group, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Number of participants reporting events is presented.
| Participants | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Number of Participants With Time to Recovery From Index Exacerbation Using EXACT- PRO Tool | 141 | 11 | 54 | 50 | 45 | 34 | 149 |
Severity of subsequent HCRU-defined exacerbations defined by EXACT was defined as the highest EXACT Total Score (not using the 3-day Rolling Average) during the period from date of onset of the subsequent HCRU-exacerbation until date of EXACT-defined recovery of subsequent exacerbation. EXACT-PRO, 14-item instrument to capture occurrence, frequency, severity, and duration of exacerbations using an eDiary. Total score ranges from 0-100, higher score indicates more severe condition. For participants with more than one subsequent exacerbation, severity was calculated for each subsequent exacerbation.
| Scores on a scale | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Moderate/Severe, n=66, 3, 23, 25, 26, 15, 78 | 53.3 ± 12.16 | 64.6 ± 25.20 | 59.8 ± 12.82 | 50.5 ± 10.76 | 47.5 ± 13.95 | 57.6 ± 10.30 | 51.9 ± 10.78 |
| Moderate, n=55, 3, 15, 23, 17, 10, 63 | 53.1 ± 11.54 | 60.0 ± 26.56 | 57.4 ± 11.08 | 50.0 ± 11.15 | 46.3 ± 14.20 | 53.8 ± 9.28 | 50.0 ± 10.17 |
| Severe, n=13, 1, 9, 3, 10, 6, 20 | 54.0 ± 15.53 | 83.0 ± NA | 64.0 ± 15.01 | 55.3 ± 5.69 | 49.5 ± 13.95 | 64.1 ± 8.99 | 58.8 ± 10.34 |
The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score is calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating severe condition. The percentage of responders using the CAT is defined as number of participants with a decrease from Baseline in CAT Total Score \>=2 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Percentage of responders using CAT was derived only for participants with a Baseline CAT Total Score \>=2. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.
| Percentage of responders | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Day 28 | 32 | 36 | 34 | 39 | 38 | 34 | 25 |
| Day 56 | 63 | 50 | 73 | 61 | 69 | 55 | 61 |
| Day 84 | 70 | 55 | 78 | 65 | 72 | 60 | 66 |
The CAT is a short, self-completed, 8-item questionnaire, each item was rated on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment). The total CAT score was calculated by summing the scores of all items and ranges from 0 to 40, higher scores indicating more severe condition. Baseline (Day 1) is defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in CAT Total Score is defined as CAT Total Score on Days 28, 56 and 84 minus Baseline CAT Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI has been presented.
| Scores on a scale | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Day 28, n=234, 19, 86, 80, 77, 74, 229 | -4.7 (-5.6 to -3.8) | -2.3 (-5.1 to 0.5) | -4.0 (-5.4 to -2.7) | -3.9 (-5.4 to -2.4) | -5.1 (-6.5 to -3.7) | -3.1 (-4.5 to -1.6) | -4.7 (-5.6 to -3.8) |
| Day 56, n=231, 20, 78, 77, 76, 69, 222 | -4.2 (-5.2 to -3.3) | -1.9 (-4.7 to 1.0) | -3.4 (-5.0 to -1.9) | -4.5 (-6.0 to -2.9) | -4.8 (-6.4 to -3.4) | -3.8 (-5.5 to -2.3) | -4.4 (-5.4 to -3.5) |
| Day 84, n=218, 17, 75, 75, 69, 62, 213 | -4.6 (-5.6 to -3.6) | -2.7 (-6.0 to 0.3) | -3.5 (-5.0 to -1.9) | -5.1 (-6.7 to -3.5) | -4.7 (-6.3 to -3.1) | -3.8 (-5.4 to -2.1) | -4.2 (-5.2 to -3.2) |
SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to the SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. The percentage of responders on the SGRQ Total Score was derived for participants with a Baseline SGRQ Total Score \>=4. Percentage of responders on the SGRQ Total Score is defined as number of participants with a decrease from Baseline in SGRQ Total Score \>=4 on or before Days 28, 56 and 84 divided by total number of participants in the MITT population. Analysis was performed using a separate Bayesian logistic regression for each time point adjusting for treatment group, smoking status at baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in the previous 12 months and gender.
| Percentage of responders | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Day 28 | 21 | 14 | 19 | 26 | 32 | 24 | 21 |
| Day 56 | 50 | 36 | 56 | 55 | 60 | 49 | 53 |
| Day 84 | 61 | 50 | 66 | 63 | 68 | 57 | 62 |
SGRQ-C is a 40-item questionnaire designed specifically to focus on COPD participants and was scored equivalent to SGRQ Total Score, ranging from 0 to 100, where higher scores reflect worse health-related quality of life. Scores on a scale were calculated as 100 multiplied by summed weights from positive items in questionnaire divided by sum of weights of all items in questionnaire. Baseline (Day 1) is defined as latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline in SGRQ Total Score is defined as SGRQ Total Score on Days 28, 56 and 84 minus Baseline SGRQ Total Score. Analysis was performed using Bayesian repeated measures model adjusting for Baseline by visit interaction, treatment by visit interaction, smoking status at Baseline, region, severity of index exacerbation, number of moderate/severe exacerbations in previous 12 months and gender. Posterior adjusted median change from Baseline and 95% HPD CrI was presented
| Scores on a scale | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Day 28, n=232, 19, 86, 78, 77, 72, 225 | -7.7 (-9.8 to -5.7) | -5.7 (-12.2 to 0.5) | -8.2 (-11.4 to -5.1) | -10.6 (-13.8 to -7.1) | -10.9 (-14.2 to -7.6) | -7.8 (-11.2 to -4.3) | -7.9 (-9.9 to -5.9) |
| Day 56, n=227, 20, 78, 77, 74, 68, 219 | -8.0 (-10.2 to -6.0) | -3.9 (-10.4 to 2.8) | -9.3 (-12.5 to -5.9) | -10.7 (-14.1 to -7.3) | -11.3 (-14.6 to -7.6) | -8.9 (-12.6 to -5.5) | -8.4 (-10.6 to -6.3) |
| Day 84, n=218, 17, 74, 74, 69, 60, 209 | -9.1 (-11.3 to -6.8) | -6.6 (-13.6 to 0.3) | -9.3 (-12.8 to -6.0) | -11.3 (-14.8 to -7.7) | -10.9 (-14.4 to -7.2) | -9.4 (-13.1 to -5.5) | -7.9 (-10.1 to -5.7) |
Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Rescue medication use was recorded as the number of occasions of rescue medication use each day. The mean number of occasions of rescue medication use per day is defined as sum of the number of occasions of rescue medication use each day within the time-period divided by the total number of days with non-missing values within the time-period. Over the 12-Week treatment period is defined as Day 1 to Day of last dose.
| No. of occasions of rescue use per day | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Week 1, n=254, 21, 87, 88, 80, 79, 254 | 1.699 ± 1.7674 | 2.112 ± 2.2977 | 1.633 ± 1.4320 | 1.926 ± 2.1569 | 1.670 ± 1.5728 | 1.917 ± 1.9298 | 1.747 ± 1.7332 |
| Week 2, n=259, 21, 88, 89, 80, 82, 252 | 1.650 ± 1.8711 | 2.231 ± 2.7169 | 1.469 ± 1.4036 | 1.712 ± 2.0310 | 1.497 ± 1.5700 | 1.611 ± 1.7717 | 1.587 ± 1.6531 |
| Week 3, n=256, 21, 90, 88, 80, 81, 245 | 1.729 ± 1.8157 | 2.021 ± 2.2926 | 1.495 ± 1.3943 | 1.693 ± 1.9679 | 1.488 ± 1.6611 | 1.742 ± 1.8380 | 1.655 ± 1.7430 |
| Week 4, n=250, 21, 89, 87, 81, 77, 243 | 1.684 ± 1.7706 | 2.190 ± 2.3657 | 1.514 ± 1.5022 | 1.720 ± 2.0083 | 1.489 ± 1.6734 | 2.009 ± 2.0506 | 1.707 ± 1.7512 |
| Week 5, n=251, 20, 88, 85, 78, 76, 240 | 1.735 ± 1.8662 | 2.329 ± 2.6394 | 1.533 ± 1.5706 | 1.750 ± 2.0380 | 1.535 ± 1.8384 | 1.949 ± 1.9685 | 1.737 ± 1.8030 |
| Week 6, n=250, 20, 86, 84, 78, 72, 234 | 1.741 ± 1.9543 | 2.378 ± 2.6904 | 1.382 ± 1.4000 | 1.792 ± 2.0822 | 1.636 ± 1.8042 | 1.936 ± 2.0729 | 1.780 ± 1.8083 |
| Week 7, n=250, 20, 85, 83, 77, 71, 231 | 1.703 ± 1.9914 | 2.479 ± 2.6976 | 1.531 ± 1.6374 | 1.697 ± 2.0769 | 1.628 ± 1.8741 | 1.899 ± 2.1694 | 1.826 ± 1.8778 |
| Week 8, n=250, 20, 84, 83, 77, 71, 231 | 1.656 ± 1.8606 | 2.736 ± 3.1579 | 1.553 ± 1.5884 | 1.616 ± 1.9444 | 1.572 ± 1.8294 | 2.006 ± 2.2242 | 1.824 ± 1.8397 |
| Week 9, n=244, 20, 82, 81, 76, 71, 229 | 1.708 ± 1.8709 | 2.765 ± 3.1104 | 1.608 ± 1.7699 | 1.658 ± 2.0646 | 1.720 ± 1.8918 | 1.953 ± 2.1838 | 1.775 ± 1.8753 |
| Week 10, n=241, 20, 81, 80, 73, 71, 227 | 1.698 ± 1.9023 | 2.543 ± 2.8753 | 1.589 ± 1.6571 | 1.596 ± 1.9809 | 1.546 ± 1.8824 | 1.927 ± 2.1613 | 1.705 ± 1.7646 |
| Week 11, n=241, 20, 79, 80, 73, 71, 226 | 1.729 ± 1.9406 | 2.164 ± 2.2504 | 1.404 ± 1.4897 | 1.602 ± 1.9435 | 1.672 ± 1.9447 | 1.926 ± 2.3243 | 1.716 ± 1.7421 |
| Week 12, n=240, 20, 78, 80, 73, 70, 225 | 1.666 ± 1.7913 | 2.386 ± 2.8157 | 1.414 ± 1.3920 | 1.671 ± 1.9612 | 1.712 ± 1.9532 | 1.790 ± 2.1140 | 1.731 ± 1.7245 |
| Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 1.684 ± 1.6903 | 2.330 ± 2.4715 | 1.553 ± 1.4044 | 1.750 ± 1.9048 | 1.620 ± 1.5994 | 1.921 ± 1.9201 | 1.733 ± 1.6618 |
Albuterol (Salbutamol) MDI or nebules was used as a rescue medication. Percentage of Rescue-Free Days is defined as sum of the number of days where the number of occasions of rescue medication use is zero within the time-period divided by total number of days with non-missing values within the time-period multiplied by 100 where the time-period is defined as follows: Week 1: Day 1-7; Week 2: Day 8 - 14; Week 3: Day 15-21; Week 4: Day 22-28; Week 5: Day 29-35; Week 6: Day 36-42; Week 7: Day 43-49; Week 8: Day 50-56; Week 9: Day 57-63; Week 10: Day 64-70; Week 11: Day 71-77; Week 12: Day 78 to Day of last dose; Over the 12-Week: Day 1 to Day of last dose.
| Percentage of rescue free days | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Week 1, n=254, 21, 87, 88, 80, 79, 254 | 34.898 ± 37.7118 | 36.076 ± 44.3182 | 29.849 ± 38.3385 | 33.392 ± 39.7372 | 32.583 ± 38.3577 | 34.453 ± 35.9802 | 29.779 ± 36.1498 |
| Week 2, n=259, 21, 88, 89, 80, 82, 252 | 41.002 ± 40.9566 | 40.819 ± 46.7899 | 32.145 ± 41.2227 | 43.017 ± 43.9884 | 38.573 ± 40.3629 | 40.595 ± 41.1717 | 33.639 ± 38.9767 |
| Week 3, n=256, 21, 90, 88, 80, 81, 245 | 38.204 ± 39.0621 | 38.776 ± 44.0612 | 31.643 ± 38.0943 | 39.964 ± 40.3936 | 41.191 ± 42.1751 | 34.923 ± 40.4026 | 33.006 ± 38.4986 |
| Week 4, n=250, 21, 89, 87, 81, 77, 243 | 39.678 ± 40.8359 | 35.376 ± 43.9405 | 32.531 ± 39.0078 | 42.202 ± 43.0692 | 43.194 ± 41.0201 | 30.986 ± 38.5941 | 32.394 ± 39.0174 |
| Week 5, n=251, 20, 88, 85, 78, 76, 240 | 38.262 ± 40.7807 | 35.005 ± 41.8344 | 35.552 ± 40.5745 | 41.682 ± 41.3648 | 41.026 ± 42.1584 | 33.912 ± 37.9973 | 33.168 ± 39.0654 |
| Week 6, n=250, 20, 86, 84, 78, 72, 234 | 40.287 ± 42.2167 | 37.870 ± 40.2125 | 35.384 ± 40.9175 | 41.720 ± 44.0117 | 39.196 ± 41.6575 | 35.519 ± 42.2122 | 32.351 ± 39.2542 |
| Week 7, n=250, 20, 85, 83, 77, 71, 231 | 41.373 ± 43.4266 | 32.145 ± 43.1992 | 35.634 ± 41.3319 | 45.266 ± 43.5910 | 40.409 ± 42.0560 | 38.232 ± 41.0296 | 31.975 ± 39.4910 |
| Week 8, n=250, 20, 84, 83, 77, 71, 231 | 42.058 ± 41.2168 | 34.290 ± 42.8300 | 33.029 ± 41.0867 | 44.118 ± 41.6682 | 42.918 ± 42.8354 | 34.811 ± 39.3585 | 32.357 ± 39.9221 |
| Week 9, n=244, 20, 82, 81, 76, 71, 229 | 39.268 ± 40.5300 | 32.145 ± 44.6657 | 32.759 ± 39.2972 | 42.505 ± 41.2121 | 39.476 ± 42.2376 | 36.823 ± 42.3513 | 33.606 ± 39.4690 |
| Week 10, n=241, 20, 81, 80, 73, 71, 227 | 40.608 ± 41.0492 | 35.000 ± 42.3430 | 32.456 ± 40.7192 | 43.396 ± 42.3040 | 41.492 ± 42.1984 | 37.024 ± 41.2291 | 33.483 ± 40.1924 |
| Week 11, n=241, 20, 79, 80, 73, 71, 226 | 39.701 ± 41.9689 | 38.575 ± 44.2366 | 35.624 ± 42.6625 | 42.859 ± 41.7845 | 39.337 ± 42.3061 | 39.841 ± 43.7237 | 33.127 ± 39.1842 |
| Week 12, n=240, 20, 78, 80, 73, 70, 225 | 41.390 ± 40.8871 | 39.415 ± 45.0442 | 37.369 ± 40.2613 | 41.300 ± 39.8199 | 39.981 ± 40.8296 | 42.236 ± 42.1567 | 33.906 ± 38.4851 |
| Over 12 Week, n=273, 21, 91, 91, 86, 83, 268 | 39.743 ± 36.8957 | 35.533 ± 39.0694 | 33.590 ± 36.6456 | 40.441 ± 37.6285 | 39.631 ± 36.5157 | 35.820 ± 34.6377 | 32.743 ± 33.9362 |
Plasma samples were collected at indicated time points and analyzed for concentrations of Nemiralisb. Pharmacokinetic (PK) Population consists of all participants in the Safety population who had at least 1 non-missing PK assessment (Non-quantifiable \[NQ\] values will be considered as non-missing values). Participants were summarized according to the treatment that they actually received.
| Picograms per milliliter | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|
| Day 14, Pre-dose, n=2, 19, 24, 16, 18, 69 | 113.6 ± 6 | 62.0 ± 46 | 142.8 ± 44 | 416.0 ± 59 | 687.3 ± 53 | 1069.6 ± 70 |
| Day 14, 0-1 hour, n=4, 19, 24, 15, 18, 67 | 54.9 ± 43 | 109.9 ± 51 | 253.7 ± 73 | 767.6 ± 71 | 1492.0 ± 59 | 1972.0 ± 110 |
| Day 14, >1-6 hours, n=4, 20, 23, 15, 18, 65 | 35.0 ± 57 | 93.1 ± 58 | 231.8 ± 53 | 657.0 ± 61 | 1146.7 ± 56 | 1622.7 ± 90 |
| Day 28, Pre-dose, n=2, 18, 23, 16, 16, 67 | 23.6 ± 24 | 60.5 ± 45 | 129.4 ± 46 | 315.6 ± 85 | 528.3 ± 110 | 937.6 ± 101 |
| Day 28, 0-1 hour, n=3, 19, 23, 16, 15, 63 | 36.2 ± 26 | 104.9 ± 70 | 253.3 ± 52 | 807.0 ± 66 | 1552.2 ± 83 | 1717.6 ± 114 |
| Day 28, >1-6 hours, n=3, 18, 23, 16, 14, 64 | 28.1 ± 15 | 85.4 ± 40 | 211.4 ± 41 | 598.8 ± 39 | 1079.5 ± 80 | 1388.1 ± 101 |
Plasma samples were collected at indicated time points and analyzed.
| Hours*picograms per milliliter | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|
| Area Under the Concentration Time Curve (AUC) From Time Zero to 24 Hours [AUC(0-24)] of Nemiralisib | NA ± NA | NA ± NA | NA ± NA | NA ± NA | NA ± NA | NA ± NA |
Plasma samples were collected at indicated time points and analyzed.
| Hours*picograms per milliliter | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|
| AUC From Time Zero to Time 't' [AUC(0-t)] of Nemiralisib | NA ± NA | NA ± NA | NA ± NA | NA ± NA | NA ± NA | NA ± NA |
Plasma samples were collected at indicated time points and analyzed.
| Picograms per milliliter | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|
| Maximum Observed Plasma Drug Concentration (Cmax) of Nemiralisib | NA ± NA | NA ± NA | NA ± NA | NA ± NA | NA ± NA | NA ± NA |
Plasma samples were collected at indicated time points and analyzed.
| Hours | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|
| Time to Reach Cmax (Tmax) of Nemiralisib | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) |
Plasma samples were collected at indicated time points and analyzed.
| Picograms per milliliter | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|
| Plasma Drug Concentration at Pre-dose (Ctrough) of Nemiralisib | NA ± NA | NA ± NA | NA ± NA | NA ± NA | NA ± NA | NA ± NA |
An AE is any untoward medical occurrence in a clinical investigation subject, 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, is a congenital anomaly/ birth effect and other important medical events. Safety Population consists of all randomized participants who received at least one dose of study treatment. Participants were summarized according to treatment that they actually received.
| Participants | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Any non-SAE | 31 | 1 | 14 | 19 | 25 | 36 | 101 |
| Any SAE | 23 | 2 | 9 | 13 | 16 | 6 | 26 |
| Any AESI | 9 | 0 | 10 | 10 | 21 | 29 | 93 |
The DBP, SBP and pulse rate were measured with participants seated at least 5 minutes before the assessments. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.
| Participants | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| DBP, To low | 8 | 3 | 3 | 0 | 4 | 4 | 7 |
| DBP, To within range/no change | 260 | 17 | 85 | 91 | 79 | 82 | 256 |
| DBP, To high | 3 | 1 | 3 | 1 | 5 | 2 | 3 |
| Pulse rate, To low | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Pulse rate,To within range/no change | 265 | 21 | 84 | 90 | 82 | 83 | 258 |
| Pulse rate, To high | 5 | 0 | 7 | 2 | 6 | 5 | 8 |
| SBP, To low | 11 | 1 | 5 | 3 | 2 | 3 | 8 |
| SBP, To withinn range/no change | 250 | 18 | 83 | 82 | 79 | 80 | 239 |
| SBP, To high | 10 | 2 | 3 | 7 | 8 | 6 | 19 |
A single 12-lead ECG with a 15-second rhythm strip was obtained using an ECG machine that automatically calculated the heart rate and measured PR, QRS, QT and corrected QT (QTc) intervals. Abnormal ECG findings are presented.
| Participants | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Screening | 93 | 10 | 25 | 37 | 28 | 21 | 86 |
| Day 14 | 88 | 8 | 24 | 33 | 29 | 18 | 74 |
| Day 84 | 79 | 8 | 22 | 27 | 24 | 18 | 64 |
| Day 112 | 77 | 11 | 28 | 28 | 25 | 20 | 75 |
| Early withdrawal | 3 | 0 | 2 | 1 | 3 | 1 | 4 |
Blood samples were collected for the analysis of clinical chemistry parameters including: blood urea nitrogen (BUN), creatinine (Crt), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total and direct bilirubin, total protein and albumin (Alb). Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.
| Participants | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Alb,To low, n=266, 21, 91, 90, 87, 85, 263 | 2 | 0 | 0 | 0 | 1 | 1 | 2 |
| Alb,w/in range/no change,n=266,21,91,90,87,85,263 | 264 | 21 | 90 | 90 | 85 | 84 | 261 |
| Alb,To high,n=266,21,91,90,87,85,263 | 0 | 0 | 1 | 0 | 1 | 0 | 0 |
| Cal,To low, n=266, 21, 90, 90, 87, 85, 263 | 1 | 0 | 0 | 0 | 0 | 1 | 1 |
| Cal,w/in range/no change,n=266,21,90,90,87,85,263 | 265 | 21 | 90 | 90 | 87 | 84 | 262 |
| Cal,To high, n=266,21,90,90,87,85,263 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Crt,To low, n=266, 21, 91, 90, 87, 85, 263 | 27 | 3 | 10 | 7 | 4 | 9 | 32 |
| Crt,w/in range/no change,n=266,21,91,90,87,85,263 | 237 | 18 | 81 | 82 | 80 | 76 | 231 |
| Crt,To high, n=266,21,91,90,87,85,263 | 2 | 0 | 0 | 1 | 3 | 0 | 0 |
| Glu,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Glu,w/in range/no change,n=266,21,91,90,87,85,263 | 266 | 21 | 91 | 89 | 87 | 85 | 263 |
| Glu,To high, n=266,21,91,90,87,85,263 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Pot,To low, n=266, 21, 90, 90, 87, 85, 263 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Pot,w/in range/no change,n=266,21,90,90,87,85,263 | 264 | 21 | 90 | 90 | 86 | 84 | 262 |
| Pot,To high, n=266,21,90,90,87,85,263 | 2 | 0 | 0 | 0 | 1 | 1 | 1 |
| Sod,To low, n=266, 21, 91, 90, 87, 85, 263 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Sod,w/in range/no change,n=266,21,91,90,87,85,263 | 266 | 21 | 91 | 90 | 87 | 85 | 263 |
| Sod,To high, n=266,21,91,90,87,85,263 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| BUN,To low, n=266, 21, 91, 90, 87, 85, 263 | 7 | 0 | 3 | 2 | 2 | 3 | 6 |
| BUN,w/in range/no change,n=266,21,91,90,87,85,263 | 256 | 21 | 88 | 86 | 85 | 82 | 253 |
| BUN,To high, n=266,21,91,90,87,85,263 | 3 | 0 | 0 | 2 | 0 | 0 | 4 |
Blood samples were collected for the analysis of hematology parameters including: platelets (Pla), red blood cells count, Hemoglobin (Hb), Hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), percentage reticulocytes, neutrophils (Neu), lymphocytes (Lym), monocytes, eosinophils, leukocytes (Leu) and basophils. Participants are counted in the worst case category if their value changes to (low, within range or no change, or high). Participants whose value category was unchanged (e.g., High to High), or whose value became within range, are recorded in the "To w/in Range or No Change" category. Participants are counted twice if the participant has values that changed "To Low" and "To High", so the percentages may not add to 100%. Participants with missing baseline value are assumed to have within range value.
| Participants | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Hb,To low, n=260, 20, 90, 90, 84, 81, 254 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Hb,w/in range/no change,n=260,20,90,90,84,81,254 | 260 | 20 | 90 | 90 | 84 | 81 | 253 |
| Hb,To high,n=260, 20, 90, 90, 84, 81, 254 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Leu,To low,n=259, 20, 90, 90, 83, 78, 251 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Leu,w/in range/no change,n=259,20,90,90,83,78,251 | 211 | 16 | 81 | 74 | 63 | 62 | 201 |
| Leu,To high, n=259,20,90,90,83,78,251 | 48 | 4 | 9 | 16 | 20 | 16 | 50 |
| Lym,To low, n=256, 20, 85, 88, 82, 77, 249 | 8 | 1 | 6 | 7 | 7 | 2 | 11 |
| Lym,w/in range/no change,n=256,20,85,88,82,77,249 | 239 | 19 | 79 | 76 | 70 | 73 | 226 |
| Lym,To high,n=256,20,85,88,82,77,249 | 9 | 0 | 0 | 5 | 5 | 2 | 12 |
| Neu, To low, n=256,20,85,88,82,77,249 | 3 | 0 | 1 | 1 | 0 | 0 | 2 |
| Neu,w/in range/no change,n=256,20,85,88,82,77,249 | 215 | 17 | 73 | 76 | 68 | 60 | 213 |
| Neu,To high, n=256,20,85,88,82,77,249 | 38 | 3 | 11 | 11 | 14 | 17 | 34 |
| Pla,To low, n=253, 19, 88, 90, 84, 78, 245 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Pla,w/in range/no change,n=253,19,88,90,84,78,245 | 253 | 19 | 88 | 90 | 84 | 78 | 245 |
| Pla,To high, n=253,19,88,90,84,78,245 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Participants reporting acute COPD exacerbations during the study period has been presented.
| Participants | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Number of Participants Reporting COPD Exacerbations | 8 | 1 | 6 | 4 | 4 | 3 | 17 |
Collected over Non-serious AEs and SAEs were collected up to Week 24. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 1/276 (0.4%) | 23/276 (8.3%) | 31/276 (11.2%) |
| Nemiralisib 12.5 mcg | 0/22 (0%) | 2/22 (9.1%) | 1/22 (4.5%) |
| Nemiralisib 50 mcg | 3/91 (3.3%) | 9/91 (9.9%) | 14/91 (15.4%) |
| Nemiralisib 100 mcg | 1/92 (1.1%) | 13/92 (14.1%) | 19/92 (20.7%) |
| Nemiralisib 250 mcg | 0/90 (0%) | 16/90 (17.8%) | 25/90 (27.8%) |
| Nemiralisib 500 mcg | 0/89 (0%) | 6/89 (6.7%) | 36/89 (40.4%) |
| Nemiralisib 750 mcg | 1/278 (0.4%) | 26/278 (9.4%) | 101/278 (36.3%) |
| Event | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| Chroni obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders | 8/276 | 1/22 | 6/91 | 4/92 | 4/90 | 3/89 | 17/278 |
| DehydrationMetabolism and nutrition disorders | 0/276 | 1/22 | 0/91 | 0/92 | 0/90 | 0/89 | 0/278 |
| Renal impairmentRenal and urinary disorders | 0/276 | 1/22 | 0/91 | 0/92 | 0/90 | 0/89 | 0/278 |
| PneumoniaInfections and infestations | 4/276 | 0/22 | 1/91 | 2/92 | 3/90 | 0/89 | 1/278 |
| Angina unstableCardiac disorders | 0/276 | 0/22 | 0/91 | 1/92 | 2/90 | 0/89 | 0/278 |
| Myocardial ischaemiaCardiac disorders | 0/276 | 0/22 | 0/91 | 0/92 | 1/90 | 1/89 | 0/278 |
| Ventricular tachycardiaCardiac disorders | 0/276 | 0/22 | 0/91 | 0/92 | 0/90 | 1/89 | 0/278 |
| HaematocheziaGastrointestinal disorders | 0/276 | 0/22 | 0/91 | 0/92 | 0/90 | 1/89 | 0/278 |
| Alanine aminotransferase increasedInvestigations | 0/276 | 0/22 | 0/91 | 0/92 | 0/90 | 1/89 | 0/278 |
| Blood bilirubin increasedInvestigations | 0/276 | 0/22 | 0/91 | 0/92 | 0/90 | 1/89 | 0/278 |
| Event | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg |
|---|---|---|---|---|---|---|---|
| CoughRespiratory, thoracic and mediastinal disorders | 13/276 | 0/22 | 10/91 | 11/92 | 23/90 | 31/89 | 96/278 |
| HeadacheNervous system disorders | 23/276 | 1/22 | 6/91 | 8/92 | 4/90 | 2/89 | 15/278 |
| Oropharyngeal painRespiratory, thoracic and mediastinal disorders | 2/276 | 0/22 | 0/91 | 2/92 | 3/90 | 5/89 | 2/278 |
| Age, Continuous(Years) | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg | Total |
|---|---|---|---|---|---|---|---|---|
| Mean | 65.4 ± 7.94 | 67.8 ± 7.20 | 63.1 ± 7.61 | 65.1 ± 7.43 | 66.0 ± 6.94 | 64.9 ± 8.04 | 64.8 ± 7.61 | 65.0 ± 7.68 |
| Sex: Female, Male(Participants) | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg | Total |
|---|---|---|---|---|---|---|---|---|
| Female | 86 | 6 | 35 | 29 | 31 | 22 | 100 | 309 |
| Male | 190 | 16 | 56 | 63 | 59 | 67 | 178 | 629 |
| Race/Ethnicity, Customized(Participants) | Placebo | Nemiralisib 12.5 mcg | Nemiralisib 50 mcg | Nemiralisib 100 mcg | Nemiralisib 250 mcg | Nemiralisib 500 mcg | Nemiralisib 750 mcg | Total |
|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 2 | 0 | 2 | 1 | 2 | 2 | 6 | 15 |
| Asian-East Asian Heritage | 18 | 4 | 7 | 2 | 9 | 7 | 19 | 66 |
| Asian-South East Asian Heritage | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 4 |
| Black or African American | 2 | 1 | 2 | 1 | 0 | 2 | 6 | 14 |
| White-Arabic/North African Heritage | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 4 |
| White-White Caucasian/European Heritage | 252 | 17 | 79 | 86 | 79 | 76 | 246 | 835 |
Showing the first 100 of 162 sites across 16 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — IPD for this study is available via the Clinical Study Data Request site
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Access criteria: Access is provided after a research proposal is submitted and has received 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 ↗ · www.clinicalstudydatarequest.com
Ran from Nov 2017 to primary completion in Jan 2019, 13 months.
Results were first posted in Feb 2020, 1 year 1 month after primary completion.
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This study is terminated, as verified in Jul 2021. You cannot join it, but the record below documents what was studied.
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Pulmonary Disease, Chronic Obstructive →