A Phase 1 interventional study of Pyrimethamine and Calcium folinate in Toxoplasmosis, sponsored by GlaxoSmithKline. Completed at 1 site in Australia. Open to male participants aged 20 Years to 64 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-03-27.
Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment
Pyrimethamine in combination with a sulphonamide is known to be effective in the treatment of toxoplasmosis. However, Pyrimethamine has not been approved by the Japanese regulatory body (Pharmaceutical and Medical Devices Agency [PMDA]/ Ministry of Health, Labor and Welfare [MHLW]). The pharmacokinetics (PK) of Pyrimethamine has been investigated following administration of Sulfadoxine/Pyrimethamine tablet in healthy Japanese subjects. However, the study did not provide sufficient information for approval of Pyrimethamine in Japan; hence, PMDA has requested confirmation of the PK of Pyrimethamine in another PK study in Japanese and Caucasian healthy subjects. This study will be a single centre, open-label, parallel-group, single oral dose study to evaluate the PK, safety and tolerability of Pyrimethamine in healthy Japanese and Caucasian male subjects. Subjects will undergo a screening visit within 30 days prior to first dose of the study drug. On Day 1, subjects will be administered a single oral dose of pyrimethamine 50 milligrams (mg) along with calcium folinate 15 mg after an overnight fast of at least 10 hours. Subjects will continue to receive calcium folinate once daily until Day 8 of the treatment period. Blood sampling for PK analysis and safety assessments will be performed prior to dosing and over 22 days after dosing. Each subject will participate in the study for approximately 2 months from screening to follow-up.
29 studies on the registry are indexed under Toxoplasmosis; 8 are open to participants now.
This study's enrollment of 14 is below the median of 66 across 15 interventional studies indexed under Toxoplasmosis.
Browse Toxoplasmosis studies →GlaxoSmithKline is the lead sponsor of 3,650 studies on the registry; 118 are open to participants now.
Of its 264 completed or terminated interventional studies of FDA-regulated products, 241 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Healthy Japanese male subjects will receive a single oral dose of Pyrimethamine 50 mg in the fasted state co-administered with calcium folinate 15 mg on Day 1. Oral calcium folinate will be administered once daily until Day 8. Blood samples for PK analysis will be collected prior to administering first dose of Pyrimethamine and over 22 days post dose. Each subject will participate in the study for a duration of approximately 2 months from screening to follow-up.
Drug: Pyrimethamine · Drug: Calcium folinate
Healthy Caucasian male subjects will receive a single oral dose of Pyrimethamine 50 mg in the fasted state co-administered with calcium folinate 15 mg on Day 1. Oral calcium folinate will be administered once daily until Day 8. Blood samples for PK analysis will be collected prior to administering first dose of Pyrimethamine and over 22 days post dose. Each subject will participate in the study for a duration of approximately 2 months from screening to follow-up.
Drug: Pyrimethamine · Drug: Calcium folinate
Pyrimethamine will be available as 25 mg tablets. Subjects will be orally administered two pyrimethamine tablets on Day 1 in a fasted condition with 240 mL of water.
Calcium folinate will be available as 5 mg tablets. Subjects will be orally administered three calcium folinate tablets on Day 1 along with pyrimethamine followed by once daily administration of calcium folinate until Day 8. Each administration will be with 240 mL water.
Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants
Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. PK Population is defined as all participants who administered at least one dose of study treatment and who have PK sample taken and analyzed.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Area Under the Concentration-time Curve From Time 0 to t (AUC[0-t]) of Pyrimethamine in Healthy Japanese Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Pyrimethamine in Healthy Japanese Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Area Under the Concentration-time Curve From Time 0 to 24 (AUC[0-24]) of Pyrimethamine in Healthy Japanese Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Apparent Clearance Following Oral Dosing (CL/F) of Pyrimethamine in Healthy Japanese Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Apparent Volume of Distribution Following Oral Dosing (Vd/F) of Pyrimethamine in Healthy Japanese Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Cmax of Pyrimethamine in Healthy Caucasian Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
AUC (0-t) of Pyrimethamine in Healthy Caucasian Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
AUC (0-inf) of Pyrimethamine in Healthy Caucasian Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
AUC (0-24) of Pyrimethamine in Healthy Caucasian Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Tmax of Pyrimethamine in Healthy Caucasian Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
T1/2 of Pyrimethamine in Healthy Caucasian Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
CL/F of Pyrimethamine in Healthy Caucasian Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Vd/F of Pyrimethamine in Healthy Caucasian Male Participants
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
Time frame: Pre-dose, 1, 2, 4, 6, 12 hours post-dose on Day 1, Day 2, Day 3, Day 4, Day 6, Day 8, Day 15 and Day 22
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who take at least one dose of study treatment were included in Safety Population.
Time frame: Up to Day 23
Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea.
Blood samples were collected for the analysis of clinical chemistry parameters including glucose, sodium, calcium, potassium, and urea at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphatase, ALT and AST at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine.
Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, bilirubin and creatinine at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline of Clinical Chemistry Parameters: Protein
Blood samples were collected for the analysis of clinical chemistry parameter including protein at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes
Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and leukocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value. Data was not available as all basophil values were below the detection limit. Hence, the change from baseline in basophil values were not calculated.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline in Hematology Parameter: Reticulocytes
Blood samples were collected for the analysis of hematology parameter including reticulocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline in Hematology Parameter: Hematocrit
Blood samples were collected for the analysis of hematology parameter including hematocrit at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline in Hematology Parameter: Hemoglobin
Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin
Blood samples were collected for the analysis of hematology parameter including mean corpuscular hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume
Blood samples were collected for the analysis of hematology parameter including mean corpuscular volume at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline in Hematology Parameter: Erythrocytes
Blood samples were collected for the analysis of hematology parameter including erythrocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours)
Number of Participants With Abnormal Urinalysis Parameter
The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of can be read as Trace, + and ++ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.
Time frame: Day -1, 24, 96, 168, 336 and follow up (504 hours)
Specific Gravity at Indicated Time Points
Urine samples were collected for analysis of specific gravity of urine. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.
Time frame: Day -1, 24, 96, 168, 336 hours and follow up (504 hours)
Urine Potential of Hydrogen (pH) at Indicated Time Points
Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
Time frame: Day -1, 24, 96, 168, 336 hours and follow up (504 hours)
Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP)
Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours
Change From Baseline in Pulse Rate
Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours
Change From Baseline in Temperature
Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours
Change From Baseline of Electrocardiogram (ECG) Parameters: PR Interval, QRS Duration, QT Interval, and QT Interval Corrected for Heart Rate by Fredericia's Formula (QTcF) Interval
A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically measures PR, QRS, QT, and QTcF intervals. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours
Change From Baseline of ECG Parameter: ECG Mean Heart Rate
A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically calculates mean ECG heart rate. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
Time frame: Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours
This study was conducted in healthy Japanese and Caucasian male participants to evaluate safety, tolerability and pharmacokinetic (PK) parameters of Pyrimethamine. This study was conducted at a single center in Australia.
| Milestone | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| Started | 7 | 7 |
| Completed | 7 | 6 |
| Not completed | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
Blood samples were collected at indicated time points. The Pharmacokinetic (PK) parameters were calculated by non-compartmental analysis. PK Population is defined as all participants who administered at least one dose of study treatment and who have PK sample taken and analyzed.
| Nanogram per milliliter | Healthy Japanese Participants |
|---|---|
| Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants | 430.5 ± 13.3 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours* nanogram per milliliter | Healthy Japanese Participants |
|---|---|
| Area Under the Concentration-time Curve From Time 0 to t (AUC[0-t]) of Pyrimethamine in Healthy Japanese Male Participants | 59013.1 ± 15.3 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours* nanogram per milliliter | Healthy Japanese Participants |
|---|---|
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Pyrimethamine in Healthy Japanese Male Participants | 64670.3 ± 16.6 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours* nanogram per milliliter | Healthy Japanese Participants |
|---|---|
| Area Under the Concentration-time Curve From Time 0 to 24 (AUC[0-24]) of Pyrimethamine in Healthy Japanese Male Participants | 8756.3 ± 8.0 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours | Healthy Japanese Participants |
|---|---|
| Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants | 122.75 ± 21.499 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours | Healthy Japanese Participants |
|---|---|
| Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants | 2.000 (1.00 to 6.00) |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Milliliter per hour | Healthy Japanese Participants |
|---|---|
| Apparent Clearance Following Oral Dosing (CL/F) of Pyrimethamine in Healthy Japanese Male Participants | 773.2 ± 16.6 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Milliliter | Healthy Japanese Participants |
|---|---|
| Apparent Volume of Distribution Following Oral Dosing (Vd/F) of Pyrimethamine in Healthy Japanese Male Participants | 135330.9 ± 5.5 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Nanogram per milliliter | Healthy Caucasian Participants |
|---|---|
| Cmax of Pyrimethamine in Healthy Caucasian Male Participants | 371.1 ± 10.0 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours* nanogram per milliliter | Healthy Caucasian Participants |
|---|---|
| AUC (0-t) of Pyrimethamine in Healthy Caucasian Male Participants | 41582.0 ± 26.9 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours* nanogram per milliliter | Healthy Caucasian Participants |
|---|---|
| AUC (0-inf) of Pyrimethamine in Healthy Caucasian Male Participants | 44869.1 ± 27.0 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours* nanogram per milliliter | Healthy Caucasian Participants |
|---|---|
| AUC (0-24) of Pyrimethamine in Healthy Caucasian Male Participants | 6930.8 ± 19.3 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours | Healthy Caucasian Participants |
|---|---|
| Tmax of Pyrimethamine in Healthy Caucasian Male Participants | 1.000 (1.000 to 6.00) |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Hours | Healthy Caucasian Participants |
|---|---|
| T1/2 of Pyrimethamine in Healthy Caucasian Male Participants | 99.46 ± 20.745 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Milliliters per hour | Healthy Caucasian Participants |
|---|---|
| CL/F of Pyrimethamine in Healthy Caucasian Male Participants | 1114.4 ± 27.0 |
Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.
| Milliliters | Healthy Caucasian Participants |
|---|---|
| Vd/F of Pyrimethamine in Healthy Caucasian Male Participants | 157125.8 ± 16.8 |
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or events associated with liver injury and impaired liver function were categorized as SAE. All participants who take at least one dose of study treatment were included in Safety Population.
| Participants | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| Any AEs | 2 | 6 |
| Any SAEs | 0 | 0 |
Blood samples were collected for the analysis of clinical chemistry parameters including glucose, sodium, calcium, potassium, and urea at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Millimoles per liter | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| Glucose, 24 hours, n=7, 7 | -0.33 ± 0.403 | -0.26 ± 0.310 |
| Glucose, 96 hours, n=7, 7 | -0.43 ± 0.281 | -0.10 ± 0.200 |
| Glucose, 168 hours, n=7, 7 | -0.60 ± 0.424 | -0.37 ± 0.214 |
| Category title 4. : Glucose, 336 hours, n=7, 7 | -0.43 ± 0.335 | -0.09 ± 0.241 |
| Glucose, Follow-up (504 hours), n= 7, 6 | -0.24 ± 0.395 | 0.00 ± 0.276 |
| Calcium, 24 hours, n=7, 7 | -0.116 ± 0.0608 | -0.054 ± 0.0862 |
| Calcium, 96 hours, n=7, 7 | -0.006 ± 0.0947 | -0.033 ± 0.0670 |
| Calcium, 168 hours, n=7, 7 | -0.006 ± 0.0730 | -0.033 ± 0.0739 |
| Calcium, 336 hours, n=7, 7 | -0.083 ± 0.1224 | -0.040 ± 0.0432 |
| Calcium, Follow up (504 hours), n=7, 6 | -0.100 ± 0.0781 | -0.042 ± 0.0637 |
| Potassium, 24 hours, n=7, 7 | -0.03 ± 0.427 | 0.00 ± 0.580 |
| Potassium, 96 hours, n=7, 7 | 0.00 ± 0.356 | -0.11 ± 0.515 |
| Potassium, 168 hours, n=7, 7 | 0.01 ± 0.463 | -0.21 ± 0.241 |
| Potassium, 336 hours, n=7, 7 | -0.10 ± 0.216 | -0.21 ± 0.515 |
| Potassium, Follow up (504 hours), n=7, 6 | 0.09 ± 0.402 | -0.22 ± 0.488 |
| Sodium, 24 hours, n=7, 7 | -0.3 ± 3.55 | 0.0 ± 2.83 |
| Sodium, 96 hours, n=7, 7 | -0.6 ± 3.05 | 1.0 ± 1.73 |
| Sodium, 168 hours, n=7, 7 | -1.3 ± 2.63 | 1.7 ± 1.25 |
| Sodium, 336 hours, n=7, 7 | 0.3 ± 1.38 | -0.3 ± 1.38 |
| Sodium, Follow up (504 hours), n=7, 6 | -0.1 ± 1.86 | -0.5 ± 1.76 |
| Urea, 24 hours, n=7, 7 | 0.33 ± 0.772 | 1.01 ± 1.110 |
| Urea, 96 hours, n=7, 7 | 0.26 ± 1.190 | -0.03 ± 0.660 |
| Urea, 168 hours, n=7, 7 | 0.41 ± 1.053 | -0.26 ± 0.885 |
| Urea, 336 hours, n=7, 7 | -0.16 ± 0.896 | 1.06 ± 1.726 |
| Urea, Follow up,(504 hours) n=7, 6 | 0.99 ± 1.995 | 1.27 ± 1.317 |
Blood samples were collected for the analysis of clinical chemistry parameters including alkaline phosphatase, ALT and AST at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| International units per liter | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| Alkaline Phosphatase, 24 hours, n=7, 7 | -9.0 ± 11.60 | -3.3 ± 5.71 |
| Alkaline Phosphatase, 96 hours, n=7, 7 | -6.7 ± 10.67 | -3.1 ± 2.97 |
| Alkaline Phosphatase, 168 hours, n=7, 7 | -7.0 ± 11.56 | -4.1 ± 3.48 |
| Alkaline Phosphatase, 336 hours, n=7, 7 | -11.0 ± 12.00 | -2.9 ± 5.90 |
| Alkaline Phosphatase, Follow-up (504 hours), n=7,6 | -9.6 ± 11.18 | -9.3 ± 5.89 |
| ALT, 24 hours, n=7, 7 | -3.0 ± 5.03 | -3.3 ± 2.81 |
| ALT, 96 hours, n=7, 7 | -2.1 ± 6.23 | -5.1 ± 4.91 |
| ALT, 168 hours, n=7, 7 | 0.7 ± 5.53 | -4.4 ± 8.16 |
| ALT, 336 hours, n=7, 7 | 0.9 ± 9.84 | -3.9 ± 2.79 |
| ALT, Follow up (504 hours), n=7, 6 | 0.4 ± 11.25 | -5.3 ± 4.59 |
| AST, 24 hours, n=7, 7 | -3.4 ± 4.61 | -1.9 ± 4.56 |
| AST, 96 hours, n=7, 7 | -3.7 ± 5.12 | -4.3 ± 6.55 |
| AST, 168 hours, n=7, 7 | -2.0 ± 5.32 | -3.0 ± 7.62 |
| AST, 336 hours, n=7, 7 | 0.3 ± 9.81 | -2.4 ± 5.86 |
| AST, Follow up (504 hours), n=7, 6 | 0.0 ± 4.16 | -1.5 ± 6.83 |
Blood samples were collected for the analysis of clinical chemistry parameters including direct bilirubin, bilirubin and creatinine at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Micromoles per liter | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| Direct bilirubin, 24 hours, n=7, 7 | 0.7 ± 1.98 | 0.6 ± 0.53 |
| Direct bilirubin, 96 hours, n=7, 7 | 0.4 ± 1.27 | 0.7 ± 1.70 |
| Direct bilirubin, 168 hours, n=7, 7 | 0.6 ± 2.30 | 0.9 ± 1.35 |
| Direct bilirubin, 336 hours, n=7, 7 | -0.3 ± 1.60 | 0.9 ± 1.95 |
| Direct bilirubin, Follow-up (504 hours), n=7, 6 | -0.3 ± 1.50 | 0.3 ± 1.97 |
| Bilirubin, 24 hours, n=7, 7 | 1.4 ± 5.16 | 3.1 ± 4.56 |
| Bilirubin, 96 hours, n=7, 7 | -0.6 ± 5.83 | 2.4 ± 5.47 |
| Bilirubin, 168 hours, n=7, 7 | 0.7 ± 8.10 | 1.0 ± 5.23 |
| Bilirubin, 336 hours, n=7, 7 | -4.0 ± 5.83 | -0.3 ± 5.22 |
| Bilirubin, Follow up (504 hours), n=7, 6 | -3.4 ± 5.56 | -1.7 ± 7.06 |
| Creatinine, 24 hours, n=7, 7 | 21.7 ± 8.16 | 26.6 ± 6.68 |
| Creatinine, 96 hours, n=7, 7 | 24.4 ± 5.06 | 30.1 ± 7.84 |
| Creatinine, 168 hours, n=7, 7 | 20.9 ± 5.08 | 24.6 ± 4.83 |
| Creatinine, 336 hours, n=7, 7 | 14.1 ± 6.18 | 14.9 ± 4.71 |
| Creatinine, Follow up (504 hours), n=7, 6 | 5.6 ± 6.16 | 9.5 ± 7.77 |
Blood samples were collected for the analysis of clinical chemistry parameter including protein at indicated time points. Day -1 value was defined as Baseline for clinical chemistry parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Gram per liter | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 24 hours, n=7, 7 | -4.9 ± 4.06 | -2.3 ± 4.03 |
| 96 hours, n=7, 7 | -4.6 ± 6.80 | -2.9 ± 1.95 |
| 168 hours, n=7, 7 | -3.6 ± 7.32 | -4.1 ± 2.67 |
| 336 hours, n=7, 7 | -4.4 ± 6.29 | -2.4 ± 1.99 |
| Follow-up (504 hours), n=7, 6 | -5.4 ± 4.69 | -4.2 ± 3.54 |
Blood samples were collected for the analysis of hematology parameters including basophils, eosinophils, lymphocytes, monocytes, neutrophils, platelet and leukocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value. Data was not available as all basophil values were below the detection limit. Hence, the change from baseline in basophil values were not calculated.
| 10^9 cells per liter | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| Eosinophils, 24 hours, n=4, 3 | -0.03 ± 0.096 | 0.07 ± 0.058 |
| Eosinophils, 96 hours, n=4, 3 | -0.03 ± 0.150 | 0.00 ± 0.100 |
| Eosinophils, 168 hours, n=4, 3 | 0.00 ± 0.115 | 0.00 ± 0.100 |
| Eosinophils, 336 hours, n=3, 3 | 0.00 ± 0.100 | 0.00 ± 0.100 |
| Eosinophils, Follow up (504 hours), n=4, 2 | -0.05 ± 0.058 | -0.05 ± 0.071 |
| Lymphocytes, 24 hours, n=7, 7 | -0.27 ± 0.528 | 0.36 ± 0.251 |
| Lymphocytes, 96 hours, n=7, 7 | -0.11 ± 0.508 | 0.30 ± 0.277 |
| Lymphocytes, 168 hours, n=7, 7 | -0.10 ± 0.574 | 0.26 ± 0.276 |
| Lymphocytes, 336 hours, n=7, 7 | -0.50 ± 0.616 | 0.09 ± 0.363 |
| Lymphocytes, Follow up (504 hours), n=7, 6 | -0.41 ± 0.441 | 0.00 ± 0.514 |
| Monocytes, 24 hours, n=7, 7 | -0.11 ± 0.107 | 0.04 ± 0.113 |
| Monocytes, 96 hours, n=7, 7 | -0.04 ± 0.190 | -0.01 ± 0.227 |
| Monocytes, 168 hours, n=7, 7 | 0.01 ± 0.186 | 0.00 ± 0.153 |
| Monocytes, 336 hours, n=7, 7 | -0.09 ± 0.177 | 0.00 ± 0.115 |
| Monocytes, Follow up (504 hours), n=7, 6 | -0.06 ± 0.172 | -0.03 ± 0.216 |
| Neutrophils, 24 hours, n=7, 7 | -0.63 ± 0.939 | -0.54 ± 0.702 |
| Neutrophils, 96 hours, n=7, 7 | -0.76 ± 1.066 | -0.79 ± 0.799 |
| Neutrophils, 168 hours, n=7, 7 | -0.61 ± 1.128 | -0.69 ± 0.546 |
| Neutrophils, 336 hours, n=7, 7 | -0.93 ± 1.181 | -0.96 ± 0.516 |
| Neutrophils, Follow up (504 hours), n=7, 6 | -1.09 ± 1.299 | -0.97 ± 0.612 |
| Platelet, 24 hours, n=7, 7 | -18.3 ± 18.82 | -11.6 ± 27.99 |
| Platelet, 96 hours, n=7, 7 | -15.1 ± 20.82 | -6.3 ± 22.65 |
| Platelet, 168 hours, n=7, 7 | -20.0 ± 26.58 | -13.3 ± 38.84 |
| Platelet, 336 hours, n=7, 7 | -22.4 ± 35.09 | -27.3 ± 38.70 |
| Platelet, Follow up (504 hours), n=7, 6 | -22.9 ± 31.49 | -24.3 ± 44.96 |
| Leukocytes, 24 hours, n=7, 7 | -1.00 ± 1.441 | -0.09 ± 0.912 |
| Leukocytes, 96 hours, n=7, 7 | -0.89 ± 1.624 | -0.46 ± 1.149 |
| Leukocytes, 168 hours, n=7, 7 | -0.67 ± 1.738 | -0.36 ± 0.735 |
| Leukocytes, 336 hours, n=7, 7 | -1.50 ± 1.649 | -0.77 ± 0.911 |
| Leukocytes, Follow up (504 hours), n=7, 6 | -1.59 ± 1.757 | -0.97 ± 1.159 |
Blood samples were collected for the analysis of hematology parameter including reticulocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Proportion of reticulocytes in blood | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 24 hours, n= 7, 7 | -0.0016 ± 0.00172 | 0.0003 ± 0.00125 |
| 96 hours, n=7, 7 | 0.0017 ± 0.00544 | -0.0006 ± 0.00162 |
| 168 hours, n=7, 7 | 0.0013 ± 0.00577 | 0.0009 ± 0.00212 |
| 336 hours, n= 7, 7 | -0.0011 ± 0.00430 | 0.0003 ± 0.00335 |
| Follow up (504 hours), n=7, 6 | -0.0013 ± 0.00368 | 0.0017 ± 0.00308 |
Blood samples were collected for the analysis of hematology parameter including hematocrit at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Proportion of red blood cells in blood | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 24 hours, n= 7, 7 | 0.001 ± 0.0135 | 0.007 ± 0.0198 |
| 96 hours, n=7, 7 | 0.009 ± 0.0186 | -0.006 ± 0.0127 |
| 168 hours, n=7, 7 | -0.004 ± 0.0181 | -0.006 ± 0.0162 |
| 336 hours, n= 7, 7 | -0.014 ± 0.0190 | -0.016 ± 0.0215 |
| Follow up (504 hours), n=7, 6 | -0.036 ± 0.0230 | -0.025 ± 0.0152 |
Blood samples were collected for the analysis of hematology parameter including hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Gram per liter | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 24 hours, n= 7, 7 | 2.0 ± 2.45 | 3.0 ± 5.23 |
| 96 hours, n=7, 7 | 2.6 ± 5.71 | 0.0 ± 2.24 |
| 168 hours, n=7, 7 | 0.0 ± 5.32 | -1.7 ± 5.50 |
| 336 hours, n= 7, 7 | -4.9 ± 4.95 | -3.6 ± 4.54 |
| Follow up (504 hours), n=7, 6 | -12.1 ± 6.47 | -6.0 ± 3.22 |
Blood samples were collected for the analysis of hematology parameter including mean corpuscular hemoglobin at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Picogram | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 24 hours, n= 7, 7 | 0.0 ± 0.00 | 0.0 ± 0.00 |
| 96 hours, n=7, 7 | -0.4 ± 0.53 | 0.0 ± 0.58 |
| 168 hours, n=7, 7 | 0.0 ± 0.82 | -0.1 ± 0.69 |
| 336 hours, n= 7, 7 | 0.1 ± 0.90 | -0.3 ± 0.76 |
| Follow up (504 hours), n=7, 6 | 0.0 ± 0.58 | -0.2 ± 0.41 |
Blood samples were collected for the analysis of hematology parameter including mean corpuscular volume at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Femtoliter | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 24 hours, n= 7, 7 | -0.6 ± 0.98 | -0.7 ± 2.43 |
| 96 hours, n=7, 7 | 0.1 ± 0.90 | -1.4 ± 1.40 |
| 168 hours, n=7, 7 | -0.3 ± 1.11 | -1.1 ± 1.35 |
| 336 hours, n= 7, 7 | 0.4 ± 0.98 | -1.9 ± 1.68 |
| Follow up (504 hours), n=7, 6 | 0.4 ± 1.27 | -1.7 ± 1.21 |
Blood samples were collected for the analysis of hematology parameter including erythrocytes at indicated time points. Day -1 value was defined as Baseline for hematology parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| 10^12 cells per liter | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 24 hours, n= 7, 7 | 0.026 ± 0.0820 | 0.100 ± 0.1943 |
| 96 hours, n=7, 7 | 0.101 ± 0.1642 | 0.006 ± 0.0680 |
| 168 hours, n=7, 7 | -0.024 ± 0.2204 | -0.021 ± 0.1906 |
| 336 hours, n= 7, 7 | -0.187 ± 0.2051 | -0.079 ± 0.1901 |
| Follow up (504 hours), n=7, 6 | -0.411 ± 0.2032 | -0.183 ± 0.1229 |
The dipstick test gives results in a semi-quantitative manner, and results for urinalysis parameters of can be read as Trace, + and ++ indicating proportional concentrations in the urine sample. Only participants with abnormal findings for urinalysis at any visit has been presented.
| Participants | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| Ketones, 336 hours, ++ | 2 | 0 |
| Ketones, 336 hours, trace | 0 | 1 |
| Ketones, follow up (504 hours), + | 1 | 0 |
| Occult blood, 336 hours, + | 1 | 0 |
| Occult blood, follow up, trace | 0 | 1 |
| Protein, Day -1, trace | 0 | 1 |
| Protein, 24 hours, trace | 2 | 3 |
| Protein, 96 hours, trace | 2 | 4 |
| Protein, 168 hours, trace | 2 | 1 |
| Protein, 336 hours, trace | 3 | 3 |
Urine samples were collected for analysis of specific gravity of urine. Urinary specific gravity is a measure of the concentration of solutes in the urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine.
| Ratio | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| Day -1, n=7, 7 | 1.0127 ± 0.00856 | 1.0177 ± 0.00720 |
| 24 hours, n=7, 7 | 1.0214 ± 0.00621 | 1.0256 ± 0.00665 |
| 96 hours, n=7, 7 | 1.0211 ± 0.00832 | 1.0236 ± 0.00550 |
| 168 hours, n=7, 7 | 1.0211 ± 0.00821 | 1.0207 ± 0.00562 |
| 336 hours, n=7, 7 | 1.0193 ± 0.00871 | 1.0246 ± 0.00945 |
| Follow up (504 hours), n=7, 6 | 1.0183 ± 0.00720 | 1.0222 ± 0.00728 |
Urine samples were collected for analysis of urine pH. pH is calculated on a scale of 0 to 14, values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).
| pH | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| Day -1, n=7, 7 | 6.21 ± 0.699 | 6.86 ± 1.144 |
| 24 hours, n=7, 7 | 5.86 ± 0.244 | 5.79 ± 0.567 |
| 96 hours, n=7, 7 | 5.79 ± 0.393 | 6.07 ± 0.345 |
| 168 hours, n=7, 7 | 5.93 ± 0.535 | 6.07 ± 0.450 |
| 336 hours, n=7, 7 | 6.00 ± 0.577 | 6.00 ± 0.408 |
| Follow up (504 hours), n=7, 6 | 6.43 ± 0.673 | 6.08 ± 0.492 |
Blood pressure of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Millimeter of mercury (mmHg) | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| DBP, 4 hours, n=7, 7 | -7.0 ± 6.98 | -0.7 ± 6.92 |
| DBP, 12 hours, n=7, 7 | -5.4 ± 6.02 | -0.3 ± 8.60 |
| DBP, 24 hours, n=7, 7 | -3.9 ± 5.24 | -2.9 ± 4.74 |
| DBP, 48 hours, n=7, 7 | -3.4 ± 6.50 | 2.0 ± 2.08 |
| DBP, 72 hours, n=7, 7 | -4.0 ± 9.11 | -4.6 ± 5.13 |
| DBP, 96 hours, n=7, 7 | -5.9 ± 10.14 | -2.7 ± 9.29 |
| DBP, 120 hours, n=7, 7 | -4.1 ± 10.02 | -3.4 ± 11.16 |
| DBP, 144 hours, n=7, 7 | -7.6 ± 8.81 | -5.4 ± 7.32 |
| DBP, 168 hours, n=7, 7 | -5.1 ± 10.25 | -1.0 ± 6.68 |
| DBP, 336 hours, n=7, 7 | -5.7 ± 9.66 | -5.3 ± 4.39 |
| DBP, 504 hours, n=7, 6 | -7.3 ± 8.73 | -0.7 ± 10.01 |
| SBP, 4 hours, n=7, 7 | -0.1 ± 5.93 | 1.3 ± 7.04 |
| SBP, 12 hours, n=7, 7 | 1.4 ± 3.41 | 1.0 ± 9.73 |
| SBP, 24 hours, n=7, 7 | -1.0 ± 6.32 | -3.4 ± 11.03 |
| SBP, 48 hours, n=7, 7 | -1.9 ± 6.20 | -1.1 ± 8.55 |
| SBP, 72 hours, n=7, 7 | -1.0 ± 6.78 | -4.6 ± 11.80 |
| SBP, 96 hours, n=7, 7 | -1.4 ± 9.96 | 2.6 ± 8.48 |
| SBP, 120 hours, n=7, 7 | -6.3 ± 5.53 | 0.9 ± 7.88 |
| SBP,144 hours, n=7, 7 | -6.6 ± 7.30 | -3.3 ± 6.52 |
| SBP, 168 hours, n=7, 7 | 0.4 ± 8.18 | 0.9 ± 6.67 |
| SBP, 336 hours, n=7, 7 | -3.9 ± 11.05 | -2.6 ± 8.81 |
| SBP, 504 hours, n=7, 6 | -5.0 ± 7.92 | -1.5 ± 5.89 |
Pulse rate of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Beats per minute | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 4 hours, n=7, 7 | 3.6 ± 5.19 | 4.7 ± 6.95 |
| 12 hours, n=7, 7 | 5.0 ± 11.45 | 10.1 ± 6.74 |
| 24 hours, n=7, 7 | 3.4 ± 8.38 | -5.0 ± 4.36 |
| 48 hours, n=7, 7 | 3.4 ± 18.12 | -0.3 ± 4.39 |
| 72 hours, n=7, 7 | 4.9 ± 11.26 | -0.3 ± 4.15 |
| 96 hours, n=7, 7 | 1.4 ± 13.44 | 0.6 ± 3.21 |
| 120 hours, n=7, 7 | 1.1 ± 9.58 | 2.0 ± 6.11 |
| 144 hours, n=7, 7 | 0.1 ± 16.74 | -0.1 ± 3.24 |
| 168 hours, n=7, 7 | 4.4 ± 17.62 | 7.1 ± 7.20 |
| 336 hours, n=7, 7 | 1.0 ± 17.61 | 1.6 ± 7.50 |
| 504 hours, n=7, 6 | -2.1 ± 18.52 | 2.2 ± 6.79 |
Temperature of participants were measured at indicated time points in semi-supine position after 5 minutes rest. Day 1 (Pre-dose) value was defined as Baseline for vital sign parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Celsius | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 4 hours, n=7, 7 | -0.01 ± 0.195 | 0.27 ± 0.095 |
| 12 hours, n=7, 7 | 0.04 ± 0.172 | 0.26 ± 0.230 |
| 24 hours, n=7, 7 | -0.07 ± 0.150 | -0.01 ± 0.241 |
| 48 hours, n=7, 7 | -0.16 ± 0.190 | -0.04 ± 0.113 |
| 72 hours, n=7, 7 | -0.10 ± 0.271 | -0.10 ± 0.100 |
| 96 hours, n=7, 7 | -0.11 ± 0.212 | -0.04 ± 0.098 |
| 120 hours, n=7, 7 | -0.10 ± 0.191 | -0.17 ± 0.189 |
| 144 hours, n=7, 7 | -0.14 ± 0.223 | -0.09 ± 0.107 |
| 168 hours, n=7, 7 | -0.09 ± 0.186 | 0.01 ± 0.135 |
| 336 hours, n=7, 7 | -0.27 ± 0.315 | -0.13 ± 0.170 |
| 504 hours, n=7, 6 | -0.26 ± 0.479 | -0.07 ± 0.242 |
A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically measures PR, QRS, QT, and QTcF intervals. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Millisecond | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| PR Interval, 4 hours, n=7, 7 | -5.3 ± 4.07 | -4.6 ± 5.44 |
| PR Interval, 12 hours, n=7, 7 | -8.7 ± 10.52 | -5.9 ± 3.89 |
| PR Interval, 24 hours, n=7, 7 | -3.1 ± 8.67 | -0.1 ± 5.70 |
| PR Interval, 48 hours, n=7, 7 | -17.0 ± 33.80 | 0.3 ± 5.41 |
| PR Interval, 504 hours, n=7, 6 | -7.3 ± 10.05 | 2.2 ± 9.91 |
| QRS duration, 4 hours, n=7, 7 | -1.6 ± 1.40 | -2.1 ± 3.24 |
| QRS duration, 12 hours, n=7, 7 | -0.3 ± 3.86 | -0.6 ± 4.04 |
| QRS duration, 24 hours, n=7, 7 | 0.3 ± 2.50 | -2.0 ± 3.96 |
| QRS duration, 48 hours, n=7, 7 | 3.1 ± 11.16 | 0.4 ± 7.91 |
| QRS duration, 504 hours, n=7, 6 | -0.3 ± 3.59 | -0.8 ± 8.08 |
| QT interval, 4 hours, n=7, 7 | -4.0 ± 15.59 | -20.4 ± 14.28 |
| QT interval, 12 hours, n=7, 7 | -17.9 ± 29.17 | -21.7 ± 20.09 |
| QT interval, 24 hours, n=7, 7 | 4.3 ± 25.79 | -7.3 ± 7.48 |
| QT interval, 48 hours, n=7, 7 | 2.3 ± 21.55 | -14.7 ± 13.50 |
| QT interval, 504 hours, n=7, 6 | 14.7 ± 32.07 | -9.2 ± 22.93 |
| QTcF interval, 4 hours, n=7, 7 | -4.9 ± 10.42 | -6.6 ± 12.39 |
| QTcF interval, 12 hours, n=7, 7 | -7.7 ± 8.94 | -5.7 ± 12.72 |
| QTcF interval, 24 hours, n=7, 7 | -0.9 ± 7.71 | -0.1 ± 12.76 |
| QTcF interval, 48 hours, n=7, 7 | 11.6 ± 40.64 | -2.9 ± 12.88 |
| QTcF interval, 504 hours, n=7, 6 | 6.7 ± 12.84 | -2.2 ± 9.64 |
A single 12-lead ECG was obtained at indicated time points using an ECG machine that automatically calculates mean ECG heart rate. Day 1 (Pre-dose) value was defined as Baseline for ECG parameters. Change from Baseline was defined as difference between post-dose visit values minus Baseline value.
| Beats per minute | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| 4 hours, n=7, 7 | -2.3 ± 11.37 | 6.0 ± 6.32 |
| 12 hours, n=7, 7 | 2.3 ± 19.91 | 7.1 ± 5.37 |
| 24 hours, n=7, 7 | -5.3 ± 19.67 | 3.1 ± 6.72 |
| 48 hours, n=7, 7 | 6.7 ± 15.64 | 5.0 ± 5.32 |
| 504 hours, n=7, 6 | -7.1 ± 25.71 | 3.2 ± 7.65 |
Collected over Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Healthy Japanese Participants | 0/7 (0%) | 0/7 (0%) | 2/7 (28.6%) |
| Healthy Caucasian Participants | 0/7 (0%) | 0/7 (0%) | 6/7 (85.7%) |
| Event | Healthy Japanese Participants | Healthy Caucasian Participants |
|---|---|---|
| FolliculitisInfections and infestations | 0/7 | 1/7 |
| Upper respiratory tract infectionInfections and infestations | 0/7 | 1/7 |
| Viral infectionInfections and infestations | 1/7 | 0/7 |
| Abdominal discomfortGastrointestinal disorders | 0/7 | 1/7 |
| NauseaGastrointestinal disorders | 0/7 | 1/7 |
| HeadacheNervous system disorders | 0/7 | 1/7 |
| Tension headacheNervous system disorders | 1/7 | 0/7 |
| Catheter site painGeneral disorders | 0/7 | 1/7 |
| Musculoskeletal painMusculoskeletal and connective tissue disorders | 0/7 | 1/7 |
| Dry skinSkin and subcutaneous tissue disorders | 1/7 | 0/7 |
| Age, Continuous(Years) | Healthy Japanese Participants | Healthy Caucasian Participants | Total |
|---|---|---|---|
| Mean | 29.0 ± 3.27 | 30.7 ± 6.02 | 29.9 ± 4.74 |
| Sex: Female, Male(Participants) | Healthy Japanese Participants | Healthy Caucasian Participants | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 7 | 7 | 14 |
| Race/Ethnicity, Customized(Participants) | Healthy Japanese Participants | Healthy Caucasian Participants | Total |
|---|---|---|---|
| Asian: Japanese Heritage/East Asian | 7 | 0 | 7 |
| White/Caucasian/European heritage | 0 | 7 | 7 |
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 is available via the Clinical Study Data Request site (click on the link provided below)
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 ↗ · clinicalstudydatarequest.com
Ran from Sep 2017 to primary completion in Nov 2017, 1 month.
Results were first posted in Mar 2019, 1 year 4 months after primary completion.
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Studies of the drug tested here: Pyrimethamine