Toxoplasmosis
Conditions
Keywords
Japanese, Caucasian, pharmacokinetics, pyrimethamine, toxoplasmosis
Brief summary
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.
Interventions
DRUGPyrimethamine
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.
DRUGCalcium folinate
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
20 Years to 64 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects should be between 20 and 64 years of age inclusive, at the time of signing the informed consent. * Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. * Body weight \>= 50 kilograms (kg) and body mass index (BMI) within the range 18.5 to 30.0 kilogram per square meters (kg/m\^2) (inclusive). * Japanese or Caucasian male. * A male subject must agree to use contraception during the treatment period and until follow-up. * Japanese ethnic origin defined as having been born in Japan, having four ethnic Japanese grandparents, holding a Japanese passport or identity papers and being able to speak Japanese. Subjects should also have lived outside Japan for less than 10 years at the time of screening. * Caucasian subject will be defined as an individual having four grandparents who are all descendants of the original people of Europe. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions of the study.
Exclusion criteria
* Alanine aminotransferase (ALT) \> 1.5 times upper limit of normal (ULN). * Bilirubin \> 1.5 times ULN (isolated bilirubin \> 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35 percent). * QT interval corrected for heart rate according to Fridericia's formula (QTcF) \> 450 milliseconds (msec). * Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). * History of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data. * Abnormal blood pressure as determined by the investigator. * Hematological values: outside normal range at screening. * Serum creatinine level: outside normal range at screening visit. * Past or intended use of over-the-counter or prescription medication including herbal medications within 14 days prior to dosing. * Participation in the study would result in loss of blood or blood products in excess of 500 milliliters (mL) within 3 months. * Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day. * Current enrollment or past participation within the last 30 days before signing of consent in this clinical study involving an investigational study treatment or any other type of medical research. * Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C antibody test result at screening. Subjects with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. * Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment. Test is optional and subjects with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing. * Positive pre-study drug/alcohol screen. * Positive human immunodeficiency virus (HIV) antibody test. * Regular use of known drugs of abuse. * Regular alcohol consumption within 6 months prior to the study defined as: For an average weekly intake of \> 14 units for males. One unit is equivalent to 10 grams (g) of alcohol: a can of mid-strength (equivalent to 375 mL) beer, 1 glass (100 mL) of table wine or 1 measure (30 mL) of spirits (including rice wine). * History or regular use of tobacco- or nicotine-containing products within 6 months prior to screening. * Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants | 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 | 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. |
| Area Under the Concentration-time Curve From Time 0 to t (AUC[0-t]) of Pyrimethamine in Healthy Japanese Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-inf]) of Pyrimethamine in Healthy Japanese Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Area Under the Concentration-time Curve From Time 0 to 24 (AUC[0-24]) of Pyrimethamine in Healthy Japanese Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Apparent Clearance Following Oral Dosing (CL/F) of Pyrimethamine in Healthy Japanese Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Apparent Volume of Distribution Following Oral Dosing (Vd/F) of Pyrimethamine in Healthy Japanese Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Up to Day 23 | 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. |
| Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Change From Baseline of Clinical Chemistry Parameters: Protein | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Change From Baseline in Hematology Parameter: Reticulocytes | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Change From Baseline in Hematology Parameter: Hematocrit | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Change From Baseline in Hematology Parameter: Hemoglobin | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Tmax of Pyrimethamine in Healthy Caucasian Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Change From Baseline in Hematology Parameter: Erythrocytes | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Number of Participants With Abnormal Urinalysis Parameter | Day -1, 24, 96, 168, 336 and follow up (504 hours) | 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. |
| Specific Gravity at Indicated Time Points | Day -1, 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, 24, 96, 168, 336 hours and follow up (504 hours) | 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). |
| Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours | 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. |
| Change From Baseline in Pulse Rate | Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours | 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. |
| Change From Baseline in Temperature | Baseline (Pre-dose on Day 1), 4, 12, 24, 48, 72, 96, 120, 144, 168, 336 and 504 hours | 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. |
| 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 | Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours | 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. |
| Change From Baseline of ECG Parameter: ECG Mean Heart Rate | Baseline (Pre-dose on Day 1), 4, 12, 24, 48, and 504 hours | 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. |
| Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | Baseline (Day -1), 24, 96, 168, 336 hours and follow up (504 hours) | 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. |
| Cmax of Pyrimethamine in Healthy Caucasian Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| AUC (0-t) of Pyrimethamine in Healthy Caucasian Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| AUC (0-inf) of Pyrimethamine in Healthy Caucasian Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| AUC (0-24) of Pyrimethamine in Healthy Caucasian Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| T1/2 of Pyrimethamine in Healthy Caucasian Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| CL/F of Pyrimethamine in Healthy Caucasian Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
| Vd/F of Pyrimethamine in Healthy Caucasian Male Participants | 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 | Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis. |
Countries
Australia
Participant flow
Recruitment details
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.
Pre-assignment details
A total of 14 healthy participants were enrolled in this study.
Participants by arm
| Arm | Count |
|---|---|
| Healthy Japanese Participants Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water. | 7 |
| Healthy Caucasian Participants Healthy Caucasian male participants received a single oral dose of Pyrimethamine 50 mg tablet in the fasted state co-administered with calcium folinate 15 mg tablet on Day 1. Oral calcium folinate was administered once daily until Day 8 along with 240 mL of water. | 7 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Healthy Caucasian Participants | Total | Healthy Japanese Participants |
|---|---|---|---|
| Age, Continuous | 30.7 Years STANDARD_DEVIATION 6.02 | 29.9 Years STANDARD_DEVIATION 4.74 | 29.0 Years STANDARD_DEVIATION 3.27 |
| Race/Ethnicity, Customized Asian: Japanese Heritage/East Asian | 0 Participants | 7 Participants | 7 Participants |
| Race/Ethnicity, Customized White/Caucasian/European heritage | 7 Participants | 7 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 |
| other Total, other adverse events | 2 / 7 | 6 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 |
Outcome results
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | Apparent Clearance Following Oral Dosing (CL/F) of Pyrimethamine in Healthy Japanese Male Participants | 773.2 Milliliter per hour | Geometric Coefficient of Variation 16.6 |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | Apparent Volume of Distribution Following Oral Dosing (Vd/F) of Pyrimethamine in Healthy Japanese Male Participants | 135330.9 Milliliter | Geometric Coefficient of Variation 5.5 |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 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 Hours* nanogram per milliliter | Geometric Coefficient of Variation 8 |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 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 Hours* nanogram per milliliter | Geometric Coefficient of Variation 16.6 |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 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 Hours* nanogram per milliliter | Geometric Coefficient of Variation 15.3 |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants | 430.5 Nanogram per milliliter | Geometric Coefficient of Variation 13.3 |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants | 122.75 Hours | Geometric Coefficient of Variation 21.499 |
Primary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Japanese Participants | Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants | 2.000 Hours |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | AUC (0-24) of Pyrimethamine in Healthy Caucasian Male Participants | 6930.8 Hours* nanogram per milliliter | Geometric Coefficient of Variation 19.3 |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | AUC (0-inf) of Pyrimethamine in Healthy Caucasian Male Participants | 44869.1 Hours* nanogram per milliliter | Geometric Coefficient of Variation 27 |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | AUC (0-t) of Pyrimethamine in Healthy Caucasian Male Participants | 41582.0 Hours* nanogram per milliliter | Geometric Coefficient of Variation 26.9 |
Secondary
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
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 4 hours, n=7, 7 | -0.1 Millimeter of mercury (mmHg) | Standard Deviation 5.93 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 120 hours, n=7, 7 | -4.1 Millimeter of mercury (mmHg) | Standard Deviation 10.02 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 12 hours, n=7, 7 | 1.4 Millimeter of mercury (mmHg) | Standard Deviation 3.41 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 24 hours, n=7, 7 | -3.9 Millimeter of mercury (mmHg) | Standard Deviation 5.24 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 24 hours, n=7, 7 | -1.0 Millimeter of mercury (mmHg) | Standard Deviation 6.32 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 144 hours, n=7, 7 | -7.6 Millimeter of mercury (mmHg) | Standard Deviation 8.81 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 48 hours, n=7, 7 | -1.9 Millimeter of mercury (mmHg) | Standard Deviation 6.2 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 72 hours, n=7, 7 | -4.0 Millimeter of mercury (mmHg) | Standard Deviation 9.11 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 72 hours, n=7, 7 | -1.0 Millimeter of mercury (mmHg) | Standard Deviation 6.78 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 168 hours, n=7, 7 | -5.1 Millimeter of mercury (mmHg) | Standard Deviation 10.25 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 96 hours, n=7, 7 | -1.4 Millimeter of mercury (mmHg) | Standard Deviation 9.96 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 12 hours, n=7, 7 | -5.4 Millimeter of mercury (mmHg) | Standard Deviation 6.02 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 120 hours, n=7, 7 | -6.3 Millimeter of mercury (mmHg) | Standard Deviation 5.53 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 336 hours, n=7, 7 | -5.7 Millimeter of mercury (mmHg) | Standard Deviation 9.66 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP,144 hours, n=7, 7 | -6.6 Millimeter of mercury (mmHg) | Standard Deviation 7.3 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 96 hours, n=7, 7 | -5.9 Millimeter of mercury (mmHg) | Standard Deviation 10.14 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 168 hours, n=7, 7 | 0.4 Millimeter of mercury (mmHg) | Standard Deviation 8.18 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 504 hours, n=7, 6 | -7.3 Millimeter of mercury (mmHg) | Standard Deviation 8.73 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 336 hours, n=7, 7 | -3.9 Millimeter of mercury (mmHg) | Standard Deviation 11.05 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 48 hours, n=7, 7 | -3.4 Millimeter of mercury (mmHg) | Standard Deviation 6.5 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 504 hours, n=7, 6 | -5.0 Millimeter of mercury (mmHg) | Standard Deviation 7.92 |
| Healthy Japanese Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 4 hours, n=7, 7 | -7.0 Millimeter of mercury (mmHg) | Standard Deviation 6.98 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 504 hours, n=7, 6 | -1.5 Millimeter of mercury (mmHg) | Standard Deviation 5.89 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 4 hours, n=7, 7 | -0.7 Millimeter of mercury (mmHg) | Standard Deviation 6.92 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 12 hours, n=7, 7 | -0.3 Millimeter of mercury (mmHg) | Standard Deviation 8.6 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 24 hours, n=7, 7 | -2.9 Millimeter of mercury (mmHg) | Standard Deviation 4.74 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 48 hours, n=7, 7 | 2.0 Millimeter of mercury (mmHg) | Standard Deviation 2.08 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 72 hours, n=7, 7 | -4.6 Millimeter of mercury (mmHg) | Standard Deviation 5.13 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 96 hours, n=7, 7 | -2.7 Millimeter of mercury (mmHg) | Standard Deviation 9.29 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 120 hours, n=7, 7 | -3.4 Millimeter of mercury (mmHg) | Standard Deviation 11.16 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 144 hours, n=7, 7 | -5.4 Millimeter of mercury (mmHg) | Standard Deviation 7.32 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 168 hours, n=7, 7 | -1.0 Millimeter of mercury (mmHg) | Standard Deviation 6.68 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 336 hours, n=7, 7 | -5.3 Millimeter of mercury (mmHg) | Standard Deviation 4.39 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | DBP, 504 hours, n=7, 6 | -0.7 Millimeter of mercury (mmHg) | Standard Deviation 10.01 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 4 hours, n=7, 7 | 1.3 Millimeter of mercury (mmHg) | Standard Deviation 7.04 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 12 hours, n=7, 7 | 1.0 Millimeter of mercury (mmHg) | Standard Deviation 9.73 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 24 hours, n=7, 7 | -3.4 Millimeter of mercury (mmHg) | Standard Deviation 11.03 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 48 hours, n=7, 7 | -1.1 Millimeter of mercury (mmHg) | Standard Deviation 8.55 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 72 hours, n=7, 7 | -4.6 Millimeter of mercury (mmHg) | Standard Deviation 11.8 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 96 hours, n=7, 7 | 2.6 Millimeter of mercury (mmHg) | Standard Deviation 8.48 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 120 hours, n=7, 7 | 0.9 Millimeter of mercury (mmHg) | Standard Deviation 7.88 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP,144 hours, n=7, 7 | -3.3 Millimeter of mercury (mmHg) | Standard Deviation 6.52 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 168 hours, n=7, 7 | 0.9 Millimeter of mercury (mmHg) | Standard Deviation 6.67 |
| Healthy Caucasian Participants | Change From Baseline in Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) | SBP, 336 hours, n=7, 7 | -2.6 Millimeter of mercury (mmHg) | Standard Deviation 8.81 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Erythrocytes | 96 hours, n=7, 7 | 0.101 10^12 cells per liter | Standard Deviation 0.1642 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Erythrocytes | 336 hours, n= 7, 7 | -0.187 10^12 cells per liter | Standard Deviation 0.2051 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Erythrocytes | 168 hours, n=7, 7 | -0.024 10^12 cells per liter | Standard Deviation 0.2204 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Erythrocytes | Follow up (504 hours), n=7, 6 | -0.411 10^12 cells per liter | Standard Deviation 0.2032 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Erythrocytes | 24 hours, n= 7, 7 | 0.026 10^12 cells per liter | Standard Deviation 0.082 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Erythrocytes | Follow up (504 hours), n=7, 6 | -0.183 10^12 cells per liter | Standard Deviation 0.1229 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Erythrocytes | 24 hours, n= 7, 7 | 0.100 10^12 cells per liter | Standard Deviation 0.1943 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Erythrocytes | 96 hours, n=7, 7 | 0.006 10^12 cells per liter | Standard Deviation 0.068 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Erythrocytes | 168 hours, n=7, 7 | -0.021 10^12 cells per liter | Standard Deviation 0.1906 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Erythrocytes | 336 hours, n= 7, 7 | -0.079 10^12 cells per liter | Standard Deviation 0.1901 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hematocrit | 96 hours, n=7, 7 | 0.009 Proportion of red blood cells in blood | Standard Deviation 0.0186 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hematocrit | 336 hours, n= 7, 7 | -0.014 Proportion of red blood cells in blood | Standard Deviation 0.019 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hematocrit | 168 hours, n=7, 7 | -0.004 Proportion of red blood cells in blood | Standard Deviation 0.0181 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hematocrit | Follow up (504 hours), n=7, 6 | -0.036 Proportion of red blood cells in blood | Standard Deviation 0.023 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hematocrit | 24 hours, n= 7, 7 | 0.001 Proportion of red blood cells in blood | Standard Deviation 0.0135 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hematocrit | Follow up (504 hours), n=7, 6 | -0.025 Proportion of red blood cells in blood | Standard Deviation 0.0152 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hematocrit | 24 hours, n= 7, 7 | 0.007 Proportion of red blood cells in blood | Standard Deviation 0.0198 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hematocrit | 96 hours, n=7, 7 | -0.006 Proportion of red blood cells in blood | Standard Deviation 0.0127 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hematocrit | 168 hours, n=7, 7 | -0.006 Proportion of red blood cells in blood | Standard Deviation 0.0162 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hematocrit | 336 hours, n= 7, 7 | -0.016 Proportion of red blood cells in blood | Standard Deviation 0.0215 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hemoglobin | 96 hours, n=7, 7 | 2.6 Gram per liter | Standard Deviation 5.71 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hemoglobin | 336 hours, n= 7, 7 | -4.9 Gram per liter | Standard Deviation 4.95 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hemoglobin | 168 hours, n=7, 7 | 0.0 Gram per liter | Standard Deviation 5.32 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hemoglobin | Follow up (504 hours), n=7, 6 | -12.1 Gram per liter | Standard Deviation 6.47 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Hemoglobin | 24 hours, n= 7, 7 | 2.0 Gram per liter | Standard Deviation 2.45 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hemoglobin | Follow up (504 hours), n=7, 6 | -6.0 Gram per liter | Standard Deviation 3.22 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hemoglobin | 24 hours, n= 7, 7 | 3.0 Gram per liter | Standard Deviation 5.23 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hemoglobin | 96 hours, n=7, 7 | 0.0 Gram per liter | Standard Deviation 2.24 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hemoglobin | 168 hours, n=7, 7 | -1.7 Gram per liter | Standard Deviation 5.5 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Hemoglobin | 336 hours, n= 7, 7 | -3.6 Gram per liter | Standard Deviation 4.54 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | 96 hours, n=7, 7 | -0.4 Picogram | Standard Deviation 0.53 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | 336 hours, n= 7, 7 | 0.1 Picogram | Standard Deviation 0.9 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | 168 hours, n=7, 7 | 0.0 Picogram | Standard Deviation 0.82 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | Follow up (504 hours), n=7, 6 | 0.0 Picogram | Standard Deviation 0.58 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | 24 hours, n= 7, 7 | 0.0 Picogram | Standard Deviation 0 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | Follow up (504 hours), n=7, 6 | -0.2 Picogram | Standard Deviation 0.41 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | 24 hours, n= 7, 7 | 0.0 Picogram | Standard Deviation 0 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | 96 hours, n=7, 7 | 0.0 Picogram | Standard Deviation 0.58 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | 168 hours, n=7, 7 | -0.1 Picogram | Standard Deviation 0.69 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin | 336 hours, n= 7, 7 | -0.3 Picogram | Standard Deviation 0.76 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | 96 hours, n=7, 7 | 0.1 Femtoliter | Standard Deviation 0.9 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | 336 hours, n= 7, 7 | 0.4 Femtoliter | Standard Deviation 0.98 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | 168 hours, n=7, 7 | -0.3 Femtoliter | Standard Deviation 1.11 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | Follow up (504 hours), n=7, 6 | 0.4 Femtoliter | Standard Deviation 1.27 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | 24 hours, n= 7, 7 | -0.6 Femtoliter | Standard Deviation 0.98 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | Follow up (504 hours), n=7, 6 | -1.7 Femtoliter | Standard Deviation 1.21 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | 24 hours, n= 7, 7 | -0.7 Femtoliter | Standard Deviation 2.43 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | 96 hours, n=7, 7 | -1.4 Femtoliter | Standard Deviation 1.4 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | 168 hours, n=7, 7 | -1.1 Femtoliter | Standard Deviation 1.35 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Mean Corpuscular Volume | 336 hours, n= 7, 7 | -1.9 Femtoliter | Standard Deviation 1.68 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Reticulocytes | 96 hours, n=7, 7 | 0.0017 Proportion of reticulocytes in blood | Standard Deviation 0.00544 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Reticulocytes | 336 hours, n= 7, 7 | -0.0011 Proportion of reticulocytes in blood | Standard Deviation 0.0043 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Reticulocytes | 168 hours, n=7, 7 | 0.0013 Proportion of reticulocytes in blood | Standard Deviation 0.00577 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Reticulocytes | Follow up (504 hours), n=7, 6 | -0.0013 Proportion of reticulocytes in blood | Standard Deviation 0.00368 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameter: Reticulocytes | 24 hours, n= 7, 7 | -0.0016 Proportion of reticulocytes in blood | Standard Deviation 0.00172 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Reticulocytes | Follow up (504 hours), n=7, 6 | 0.0017 Proportion of reticulocytes in blood | Standard Deviation 0.00308 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Reticulocytes | 24 hours, n= 7, 7 | 0.0003 Proportion of reticulocytes in blood | Standard Deviation 0.00125 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Reticulocytes | 96 hours, n=7, 7 | -0.0006 Proportion of reticulocytes in blood | Standard Deviation 0.00162 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Reticulocytes | 168 hours, n=7, 7 | 0.0009 Proportion of reticulocytes in blood | Standard Deviation 0.00212 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameter: Reticulocytes | 336 hours, n= 7, 7 | 0.0003 Proportion of reticulocytes in blood | Standard Deviation 0.00335 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, Follow up (504 hours), n=4, 2 | -0.05 10^9 cells per liter | Standard Deviation 0.058 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, 336 hours, n=7, 7 | -0.09 10^9 cells per liter | Standard Deviation 0.177 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, 24 hours, n=4, 3 | -0.03 10^9 cells per liter | Standard Deviation 0.096 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, Follow up (504 hours), n=7, 6 | -0.06 10^9 cells per liter | Standard Deviation 0.172 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, 24 hours, n=7, 7 | -0.27 10^9 cells per liter | Standard Deviation 0.528 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, 24 hours, n=7, 7 | -0.63 10^9 cells per liter | Standard Deviation 0.939 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, Follow up (504 hours), n=7, 6 | -1.59 10^9 cells per liter | Standard Deviation 1.757 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, 96 hours, n=7, 7 | -0.76 10^9 cells per liter | Standard Deviation 1.066 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, 96 hours, n=7, 7 | -0.11 10^9 cells per liter | Standard Deviation 0.508 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, 168 hours, n=7, 7 | -0.61 10^9 cells per liter | Standard Deviation 1.128 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, 96 hours, n=4, 3 | -0.03 10^9 cells per liter | Standard Deviation 0.15 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, 336 hours, n=7, 7 | -0.93 10^9 cells per liter | Standard Deviation 1.181 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, 168 hours, n=7, 7 | -0.10 10^9 cells per liter | Standard Deviation 0.574 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, Follow up (504 hours), n=7, 6 | -1.09 10^9 cells per liter | Standard Deviation 1.299 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, 336 hours, n=7, 7 | -1.50 10^9 cells per liter | Standard Deviation 1.649 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, 24 hours, n=7, 7 | -18.3 10^9 cells per liter | Standard Deviation 18.82 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, 336 hours, n=7, 7 | -0.50 10^9 cells per liter | Standard Deviation 0.616 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, 96 hours, n=7, 7 | -15.1 10^9 cells per liter | Standard Deviation 20.82 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, 168 hours, n=4, 3 | 0.00 10^9 cells per liter | Standard Deviation 0.115 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, 168 hours, n=7, 7 | -20.0 10^9 cells per liter | Standard Deviation 26.58 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, Follow up (504 hours), n=7, 6 | -0.41 10^9 cells per liter | Standard Deviation 0.441 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, 336 hours, n=7, 7 | -22.4 10^9 cells per liter | Standard Deviation 35.09 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, 168 hours, n=7, 7 | -0.67 10^9 cells per liter | Standard Deviation 1.738 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, Follow up (504 hours), n=7, 6 | -22.9 10^9 cells per liter | Standard Deviation 31.49 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, 24 hours, n=7, 7 | -0.11 10^9 cells per liter | Standard Deviation 0.107 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, 24 hours, n=7, 7 | -1.00 10^9 cells per liter | Standard Deviation 1.441 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, 336 hours, n=3, 3 | 0.00 10^9 cells per liter | Standard Deviation 0.1 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, 96 hours, n=7, 7 | -0.04 10^9 cells per liter | Standard Deviation 0.19 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, 96 hours, n=7, 7 | -0.89 10^9 cells per liter | Standard Deviation 1.624 |
| Healthy Japanese Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, 168 hours, n=7, 7 | 0.01 10^9 cells per liter | Standard Deviation 0.186 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, Follow up (504 hours), n=7, 6 | -0.97 10^9 cells per liter | Standard Deviation 1.159 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, 24 hours, n=4, 3 | 0.07 10^9 cells per liter | Standard Deviation 0.058 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, 96 hours, n=4, 3 | 0.00 10^9 cells per liter | Standard Deviation 0.1 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, 168 hours, n=4, 3 | 0.00 10^9 cells per liter | Standard Deviation 0.1 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, 336 hours, n=3, 3 | 0.00 10^9 cells per liter | Standard Deviation 0.1 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Eosinophils, Follow up (504 hours), n=4, 2 | -0.05 10^9 cells per liter | Standard Deviation 0.071 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, 24 hours, n=7, 7 | 0.36 10^9 cells per liter | Standard Deviation 0.251 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, 96 hours, n=7, 7 | 0.30 10^9 cells per liter | Standard Deviation 0.277 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, 168 hours, n=7, 7 | 0.26 10^9 cells per liter | Standard Deviation 0.276 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, 336 hours, n=7, 7 | 0.09 10^9 cells per liter | Standard Deviation 0.363 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Lymphocytes, Follow up (504 hours), n=7, 6 | 0.00 10^9 cells per liter | Standard Deviation 0.514 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, 24 hours, n=7, 7 | 0.04 10^9 cells per liter | Standard Deviation 0.113 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, 96 hours, n=7, 7 | -0.01 10^9 cells per liter | Standard Deviation 0.227 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, 168 hours, n=7, 7 | 0.00 10^9 cells per liter | Standard Deviation 0.153 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, 336 hours, n=7, 7 | 0.00 10^9 cells per liter | Standard Deviation 0.115 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Monocytes, Follow up (504 hours), n=7, 6 | -0.03 10^9 cells per liter | Standard Deviation 0.216 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, 24 hours, n=7, 7 | -0.54 10^9 cells per liter | Standard Deviation 0.702 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, 96 hours, n=7, 7 | -0.79 10^9 cells per liter | Standard Deviation 0.799 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, 168 hours, n=7, 7 | -0.69 10^9 cells per liter | Standard Deviation 0.546 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, 336 hours, n=7, 7 | -0.96 10^9 cells per liter | Standard Deviation 0.516 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Neutrophils, Follow up (504 hours), n=7, 6 | -0.97 10^9 cells per liter | Standard Deviation 0.612 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, 24 hours, n=7, 7 | -11.6 10^9 cells per liter | Standard Deviation 27.99 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, 96 hours, n=7, 7 | -6.3 10^9 cells per liter | Standard Deviation 22.65 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, 168 hours, n=7, 7 | -13.3 10^9 cells per liter | Standard Deviation 38.84 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, 336 hours, n=7, 7 | -27.3 10^9 cells per liter | Standard Deviation 38.7 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Platelet, Follow up (504 hours), n=7, 6 | -24.3 10^9 cells per liter | Standard Deviation 44.96 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, 24 hours, n=7, 7 | -0.09 10^9 cells per liter | Standard Deviation 0.912 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, 96 hours, n=7, 7 | -0.46 10^9 cells per liter | Standard Deviation 1.149 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, 168 hours, n=7, 7 | -0.36 10^9 cells per liter | Standard Deviation 0.735 |
| Healthy Caucasian Participants | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Leukocytes, 336 hours, n=7, 7 | -0.77 10^9 cells per liter | Standard Deviation 0.911 |
| Unknown | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Basophils, 96 hours, n=0, 0 | — 10^9 cells per liter | — |
| Unknown | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Basophils, 168 hours, n=0, 0 | — 10^9 cells per liter | — |
| Unknown | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Basophils, Follow up (504 hours), n=0, 0 | — 10^9 cells per liter | — |
| Unknown | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Basophils, 24 hours, n=0, 0 | — 10^9 cells per liter | — |
| Unknown | Change From Baseline in Hematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Platelet and Leukocytes | Basophils, 336 hours, n=0, 0 | — 10^9 cells per liter | — |
Secondary
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
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 12 hours, n=7, 7 | 5.0 Beats per minute | Standard Deviation 11.45 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 120 hours, n=7, 7 | 1.1 Beats per minute | Standard Deviation 9.58 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 4 hours, n=7, 7 | 3.6 Beats per minute | Standard Deviation 5.19 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 144 hours, n=7, 7 | 0.1 Beats per minute | Standard Deviation 16.74 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 72 hours, n=7, 7 | 4.9 Beats per minute | Standard Deviation 11.26 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 168 hours, n=7, 7 | 4.4 Beats per minute | Standard Deviation 17.62 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 24 hours, n=7, 7 | 3.4 Beats per minute | Standard Deviation 8.38 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 336 hours, n=7, 7 | 1.0 Beats per minute | Standard Deviation 17.61 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 96 hours, n=7, 7 | 1.4 Beats per minute | Standard Deviation 13.44 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 504 hours, n=7, 6 | -2.1 Beats per minute | Standard Deviation 18.52 |
| Healthy Japanese Participants | Change From Baseline in Pulse Rate | 48 hours, n=7, 7 | 3.4 Beats per minute | Standard Deviation 18.12 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 504 hours, n=7, 6 | 2.2 Beats per minute | Standard Deviation 6.79 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 4 hours, n=7, 7 | 4.7 Beats per minute | Standard Deviation 6.95 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 12 hours, n=7, 7 | 10.1 Beats per minute | Standard Deviation 6.74 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 24 hours, n=7, 7 | -5.0 Beats per minute | Standard Deviation 4.36 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 48 hours, n=7, 7 | -0.3 Beats per minute | Standard Deviation 4.39 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 72 hours, n=7, 7 | -0.3 Beats per minute | Standard Deviation 4.15 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 96 hours, n=7, 7 | 0.6 Beats per minute | Standard Deviation 3.21 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 120 hours, n=7, 7 | 2.0 Beats per minute | Standard Deviation 6.11 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 144 hours, n=7, 7 | -0.1 Beats per minute | Standard Deviation 3.24 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 168 hours, n=7, 7 | 7.1 Beats per minute | Standard Deviation 7.2 |
| Healthy Caucasian Participants | Change From Baseline in Pulse Rate | 336 hours, n=7, 7 | 1.6 Beats per minute | Standard Deviation 7.5 |
Secondary
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
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline in Temperature | 12 hours, n=7, 7 | 0.04 Celsius | Standard Deviation 0.172 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 120 hours, n=7, 7 | -0.10 Celsius | Standard Deviation 0.191 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 4 hours, n=7, 7 | -0.01 Celsius | Standard Deviation 0.195 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 144 hours, n=7, 7 | -0.14 Celsius | Standard Deviation 0.223 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 72 hours, n=7, 7 | -0.10 Celsius | Standard Deviation 0.271 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 168 hours, n=7, 7 | -0.09 Celsius | Standard Deviation 0.186 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 24 hours, n=7, 7 | -0.07 Celsius | Standard Deviation 0.15 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 336 hours, n=7, 7 | -0.27 Celsius | Standard Deviation 0.315 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 96 hours, n=7, 7 | -0.11 Celsius | Standard Deviation 0.212 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 504 hours, n=7, 6 | -0.26 Celsius | Standard Deviation 0.479 |
| Healthy Japanese Participants | Change From Baseline in Temperature | 48 hours, n=7, 7 | -0.16 Celsius | Standard Deviation 0.19 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 504 hours, n=7, 6 | -0.07 Celsius | Standard Deviation 0.242 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 4 hours, n=7, 7 | 0.27 Celsius | Standard Deviation 0.095 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 12 hours, n=7, 7 | 0.26 Celsius | Standard Deviation 0.23 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 24 hours, n=7, 7 | -0.01 Celsius | Standard Deviation 0.241 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 48 hours, n=7, 7 | -0.04 Celsius | Standard Deviation 0.113 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 72 hours, n=7, 7 | -0.10 Celsius | Standard Deviation 0.1 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 96 hours, n=7, 7 | -0.04 Celsius | Standard Deviation 0.098 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 120 hours, n=7, 7 | -0.17 Celsius | Standard Deviation 0.189 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 144 hours, n=7, 7 | -0.09 Celsius | Standard Deviation 0.107 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 168 hours, n=7, 7 | 0.01 Celsius | Standard Deviation 0.135 |
| Healthy Caucasian Participants | Change From Baseline in Temperature | 336 hours, n=7, 7 | -0.13 Celsius | Standard Deviation 0.17 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, Follow-up (504 hours), n=7,6 | -9.6 International units per liter | Standard Deviation 11.18 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, 336 hours, n=7, 7 | 0.9 International units per liter | Standard Deviation 9.84 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, 96 hours, n=7, 7 | -6.7 International units per liter | Standard Deviation 10.67 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, Follow up (504 hours), n=7, 6 | 0.4 International units per liter | Standard Deviation 11.25 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, 24 hours, n=7, 7 | -3.0 International units per liter | Standard Deviation 5.03 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, 24 hours, n=7, 7 | -3.4 International units per liter | Standard Deviation 4.61 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, 336 hours, n=7, 7 | -11.0 International units per liter | Standard Deviation 12 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, 96 hours, n=7, 7 | -3.7 International units per liter | Standard Deviation 5.12 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, 96 hours, n=7, 7 | -2.1 International units per liter | Standard Deviation 6.23 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, 168 hours, n=7, 7 | -2.0 International units per liter | Standard Deviation 5.32 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, 168 hours, n=7, 7 | -7.0 International units per liter | Standard Deviation 11.56 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, 336 hours, n=7, 7 | 0.3 International units per liter | Standard Deviation 9.81 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, 168 hours, n=7, 7 | 0.7 International units per liter | Standard Deviation 5.53 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, Follow up (504 hours), n=7, 6 | 0.0 International units per liter | Standard Deviation 4.16 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, 24 hours, n=7, 7 | -9.0 International units per liter | Standard Deviation 11.6 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, Follow up (504 hours), n=7, 6 | -1.5 International units per liter | Standard Deviation 6.83 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, 24 hours, n=7, 7 | -3.3 International units per liter | Standard Deviation 5.71 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, 96 hours, n=7, 7 | -3.1 International units per liter | Standard Deviation 2.97 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, 168 hours, n=7, 7 | -4.1 International units per liter | Standard Deviation 3.48 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, 336 hours, n=7, 7 | -2.9 International units per liter | Standard Deviation 5.9 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | Alkaline Phosphatase, Follow-up (504 hours), n=7,6 | -9.3 International units per liter | Standard Deviation 5.89 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, 24 hours, n=7, 7 | -3.3 International units per liter | Standard Deviation 2.81 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, 96 hours, n=7, 7 | -5.1 International units per liter | Standard Deviation 4.91 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, 168 hours, n=7, 7 | -4.4 International units per liter | Standard Deviation 8.16 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, 336 hours, n=7, 7 | -3.9 International units per liter | Standard Deviation 2.79 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | ALT, Follow up (504 hours), n=7, 6 | -5.3 International units per liter | Standard Deviation 4.59 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, 24 hours, n=7, 7 | -1.9 International units per liter | Standard Deviation 4.56 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, 96 hours, n=7, 7 | -4.3 International units per liter | Standard Deviation 6.55 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, 168 hours, n=7, 7 | -3.0 International units per liter | Standard Deviation 7.62 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) | AST, 336 hours, n=7, 7 | -2.4 International units per liter | Standard Deviation 5.86 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, Follow up (504 hours), n=7, 6 | 5.6 Micromoles per liter | Standard Deviation 6.16 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, 24 hours, n=7, 7 | 0.7 Micromoles per liter | Standard Deviation 1.98 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, 96 hours, n=7, 7 | 0.4 Micromoles per liter | Standard Deviation 1.27 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, 168 hours, n=7, 7 | 0.6 Micromoles per liter | Standard Deviation 2.3 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, 336 hours, n=7, 7 | -0.3 Micromoles per liter | Standard Deviation 1.6 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, Follow-up (504 hours), n=7, 6 | -0.3 Micromoles per liter | Standard Deviation 1.5 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, 24 hours, n=7, 7 | 1.4 Micromoles per liter | Standard Deviation 5.16 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, 96 hours, n=7, 7 | -0.6 Micromoles per liter | Standard Deviation 5.83 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, 168 hours, n=7, 7 | 0.7 Micromoles per liter | Standard Deviation 8.1 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, 336 hours, n=7, 7 | -4.0 Micromoles per liter | Standard Deviation 5.83 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, Follow up (504 hours), n=7, 6 | -3.4 Micromoles per liter | Standard Deviation 5.56 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, 24 hours, n=7, 7 | 21.7 Micromoles per liter | Standard Deviation 8.16 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, 96 hours, n=7, 7 | 24.4 Micromoles per liter | Standard Deviation 5.06 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, 168 hours, n=7, 7 | 20.9 Micromoles per liter | Standard Deviation 5.08 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, 336 hours, n=7, 7 | 14.1 Micromoles per liter | Standard Deviation 6.18 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, Follow up (504 hours), n=7, 6 | 9.5 Micromoles per liter | Standard Deviation 7.77 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, 168 hours, n=7, 7 | 1.0 Micromoles per liter | Standard Deviation 5.23 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, 24 hours, n=7, 7 | 0.6 Micromoles per liter | Standard Deviation 0.53 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, 96 hours, n=7, 7 | 30.1 Micromoles per liter | Standard Deviation 7.84 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, 96 hours, n=7, 7 | 0.7 Micromoles per liter | Standard Deviation 1.7 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, 336 hours, n=7, 7 | -0.3 Micromoles per liter | Standard Deviation 5.22 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, 168 hours, n=7, 7 | 0.9 Micromoles per liter | Standard Deviation 1.35 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, 336 hours, n=7, 7 | 14.9 Micromoles per liter | Standard Deviation 4.71 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, 336 hours, n=7, 7 | 0.9 Micromoles per liter | Standard Deviation 1.95 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, Follow up (504 hours), n=7, 6 | -1.7 Micromoles per liter | Standard Deviation 7.06 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Direct bilirubin, Follow-up (504 hours), n=7, 6 | 0.3 Micromoles per liter | Standard Deviation 1.97 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, 168 hours, n=7, 7 | 24.6 Micromoles per liter | Standard Deviation 4.83 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, 24 hours, n=7, 7 | 3.1 Micromoles per liter | Standard Deviation 4.56 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Creatinine, 24 hours, n=7, 7 | 26.6 Micromoles per liter | Standard Deviation 6.68 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. | Bilirubin, 96 hours, n=7, 7 | 2.4 Micromoles per liter | Standard Deviation 5.47 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, 168 hours, n=7, 7 | 0.01 Millimoles per liter | Standard Deviation 0.463 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, 96 hours, n=7, 7 | -0.006 Millimoles per liter | Standard Deviation 0.0947 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, 336 hours, n=7, 7 | -0.10 Millimoles per liter | Standard Deviation 0.216 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Category title 4. : Glucose, 336 hours, n=7, 7 | -0.43 Millimoles per liter | Standard Deviation 0.335 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, Follow up (504 hours), n=7, 6 | 0.09 Millimoles per liter | Standard Deviation 0.402 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, 168 hours, n=7, 7 | -0.006 Millimoles per liter | Standard Deviation 0.073 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, 24 hours, n=7, 7 | -0.3 Millimoles per liter | Standard Deviation 3.55 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Glucose, 24 hours, n=7, 7 | -0.33 Millimoles per liter | Standard Deviation 0.403 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, 96 hours, n=7, 7 | -0.6 Millimoles per liter | Standard Deviation 3.05 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, 336 hours, n=7, 7 | -0.083 Millimoles per liter | Standard Deviation 0.1224 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, 168 hours, n=7, 7 | -1.3 Millimoles per liter | Standard Deviation 2.63 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Glucose, Follow-up (504 hours), n= 7, 6 | -0.24 Millimoles per liter | Standard Deviation 0.395 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, 336 hours, n=7, 7 | 0.3 Millimoles per liter | Standard Deviation 1.38 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, Follow up (504 hours), n=7, 6 | -0.100 Millimoles per liter | Standard Deviation 0.0781 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, Follow up (504 hours), n=7, 6 | -0.1 Millimoles per liter | Standard Deviation 1.86 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, 24 hours, n=7, 7 | 0.33 Millimoles per liter | Standard Deviation 0.772 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Glucose, 168 hours, n=7, 7 | -0.60 Millimoles per liter | Standard Deviation 0.424 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, 96 hours, n=7, 7 | 0.26 Millimoles per liter | Standard Deviation 1.19 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, 24 hours, n=7, 7 | -0.03 Millimoles per liter | Standard Deviation 0.427 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, 168 hours, n=7, 7 | 0.41 Millimoles per liter | Standard Deviation 1.053 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, 24 hours, n=7, 7 | -0.116 Millimoles per liter | Standard Deviation 0.0608 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, 336 hours, n=7, 7 | -0.16 Millimoles per liter | Standard Deviation 0.896 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, 96 hours, n=7, 7 | 0.00 Millimoles per liter | Standard Deviation 0.356 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, Follow up,(504 hours) n=7, 6 | 0.99 Millimoles per liter | Standard Deviation 1.995 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Glucose, 96 hours, n=7, 7 | -0.43 Millimoles per liter | Standard Deviation 0.281 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, Follow up,(504 hours) n=7, 6 | 1.27 Millimoles per liter | Standard Deviation 1.317 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Glucose, 24 hours, n=7, 7 | -0.26 Millimoles per liter | Standard Deviation 0.31 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Glucose, 96 hours, n=7, 7 | -0.10 Millimoles per liter | Standard Deviation 0.2 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Glucose, 168 hours, n=7, 7 | -0.37 Millimoles per liter | Standard Deviation 0.214 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Category title 4. : Glucose, 336 hours, n=7, 7 | -0.09 Millimoles per liter | Standard Deviation 0.241 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Glucose, Follow-up (504 hours), n= 7, 6 | 0.00 Millimoles per liter | Standard Deviation 0.276 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, 24 hours, n=7, 7 | -0.054 Millimoles per liter | Standard Deviation 0.0862 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, 96 hours, n=7, 7 | -0.033 Millimoles per liter | Standard Deviation 0.067 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, 168 hours, n=7, 7 | -0.033 Millimoles per liter | Standard Deviation 0.0739 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, 336 hours, n=7, 7 | -0.040 Millimoles per liter | Standard Deviation 0.0432 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Calcium, Follow up (504 hours), n=7, 6 | -0.042 Millimoles per liter | Standard Deviation 0.0637 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, 24 hours, n=7, 7 | 0.00 Millimoles per liter | Standard Deviation 0.58 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, 96 hours, n=7, 7 | -0.11 Millimoles per liter | Standard Deviation 0.515 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, 168 hours, n=7, 7 | -0.21 Millimoles per liter | Standard Deviation 0.241 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, 336 hours, n=7, 7 | -0.21 Millimoles per liter | Standard Deviation 0.515 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Potassium, Follow up (504 hours), n=7, 6 | -0.22 Millimoles per liter | Standard Deviation 0.488 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, 24 hours, n=7, 7 | 0.0 Millimoles per liter | Standard Deviation 2.83 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, 96 hours, n=7, 7 | 1.0 Millimoles per liter | Standard Deviation 1.73 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, 168 hours, n=7, 7 | 1.7 Millimoles per liter | Standard Deviation 1.25 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, 336 hours, n=7, 7 | -0.3 Millimoles per liter | Standard Deviation 1.38 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, 24 hours, n=7, 7 | 1.01 Millimoles per liter | Standard Deviation 1.11 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, 96 hours, n=7, 7 | -0.03 Millimoles per liter | Standard Deviation 0.66 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, 168 hours, n=7, 7 | -0.26 Millimoles per liter | Standard Deviation 0.885 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Urea, 336 hours, n=7, 7 | 1.06 Millimoles per liter | Standard Deviation 1.726 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Glucose, Sodium, Calcium, Potassium, and Urea. | Sodium, Follow up (504 hours), n=7, 6 | -0.5 Millimoles per liter | Standard Deviation 1.76 |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | 96 hours, n=7, 7 | -4.6 Gram per liter | Standard Deviation 6.8 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | 336 hours, n=7, 7 | -4.4 Gram per liter | Standard Deviation 6.29 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | 168 hours, n=7, 7 | -3.6 Gram per liter | Standard Deviation 7.32 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | Follow-up (504 hours), n=7, 6 | -5.4 Gram per liter | Standard Deviation 4.69 |
| Healthy Japanese Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | 24 hours, n=7, 7 | -4.9 Gram per liter | Standard Deviation 4.06 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | Follow-up (504 hours), n=7, 6 | -4.2 Gram per liter | Standard Deviation 3.54 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | 24 hours, n=7, 7 | -2.3 Gram per liter | Standard Deviation 4.03 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | 96 hours, n=7, 7 | -2.9 Gram per liter | Standard Deviation 1.95 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | 168 hours, n=7, 7 | -4.1 Gram per liter | Standard Deviation 2.67 |
| Healthy Caucasian Participants | Change From Baseline of Clinical Chemistry Parameters: Protein | 336 hours, n=7, 7 | -2.4 Gram per liter | Standard Deviation 1.99 |
Secondary
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
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 12 hours, n=7, 7 | 2.3 Beats per minute | Standard Deviation 19.91 |
| Healthy Japanese Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 48 hours, n=7, 7 | 6.7 Beats per minute | Standard Deviation 15.64 |
| Healthy Japanese Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 24 hours, n=7, 7 | -5.3 Beats per minute | Standard Deviation 19.67 |
| Healthy Japanese Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 504 hours, n=7, 6 | -7.1 Beats per minute | Standard Deviation 25.71 |
| Healthy Japanese Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 4 hours, n=7, 7 | -2.3 Beats per minute | Standard Deviation 11.37 |
| Healthy Caucasian Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 504 hours, n=7, 6 | 3.2 Beats per minute | Standard Deviation 7.65 |
| Healthy Caucasian Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 4 hours, n=7, 7 | 6.0 Beats per minute | Standard Deviation 6.32 |
| Healthy Caucasian Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 12 hours, n=7, 7 | 7.1 Beats per minute | Standard Deviation 5.37 |
| Healthy Caucasian Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 24 hours, n=7, 7 | 3.1 Beats per minute | Standard Deviation 6.72 |
| Healthy Caucasian Participants | Change From Baseline of ECG Parameter: ECG Mean Heart Rate | 48 hours, n=7, 7 | 5.0 Beats per minute | Standard Deviation 5.32 |
Secondary
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
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | 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 | PR Interval, 4 hours, n=7, 7 | -5.3 Millisecond | Standard Deviation 4.07 |
| Healthy Japanese Participants | 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 | PR Interval, 12 hours, n=7, 7 | -8.7 Millisecond | Standard Deviation 10.52 |
| Healthy Japanese Participants | 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 | PR Interval, 24 hours, n=7, 7 | -3.1 Millisecond | Standard Deviation 8.67 |
| Healthy Japanese Participants | 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 | PR Interval, 48 hours, n=7, 7 | -17.0 Millisecond | Standard Deviation 33.8 |
| Healthy Japanese Participants | 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 | PR Interval, 504 hours, n=7, 6 | -7.3 Millisecond | Standard Deviation 10.05 |
| Healthy Japanese Participants | 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 | QRS duration, 4 hours, n=7, 7 | -1.6 Millisecond | Standard Deviation 1.4 |
| Healthy Japanese Participants | 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 | QRS duration, 12 hours, n=7, 7 | -0.3 Millisecond | Standard Deviation 3.86 |
| Healthy Japanese Participants | 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 | QRS duration, 24 hours, n=7, 7 | 0.3 Millisecond | Standard Deviation 2.5 |
| Healthy Japanese Participants | 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 | QRS duration, 48 hours, n=7, 7 | 3.1 Millisecond | Standard Deviation 11.16 |
| Healthy Japanese Participants | 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 | QRS duration, 504 hours, n=7, 6 | -0.3 Millisecond | Standard Deviation 3.59 |
| Healthy Japanese Participants | 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 | QT interval, 4 hours, n=7, 7 | -4.0 Millisecond | Standard Deviation 15.59 |
| Healthy Japanese Participants | 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 | QT interval, 12 hours, n=7, 7 | -17.9 Millisecond | Standard Deviation 29.17 |
| Healthy Japanese Participants | 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 | QT interval, 24 hours, n=7, 7 | 4.3 Millisecond | Standard Deviation 25.79 |
| Healthy Japanese Participants | 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 | QT interval, 48 hours, n=7, 7 | 2.3 Millisecond | Standard Deviation 21.55 |
| Healthy Japanese Participants | 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 | QT interval, 504 hours, n=7, 6 | 14.7 Millisecond | Standard Deviation 32.07 |
| Healthy Japanese Participants | 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 | QTcF interval, 4 hours, n=7, 7 | -4.9 Millisecond | Standard Deviation 10.42 |
| Healthy Japanese Participants | 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 | QTcF interval, 12 hours, n=7, 7 | -7.7 Millisecond | Standard Deviation 8.94 |
| Healthy Japanese Participants | 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 | QTcF interval, 24 hours, n=7, 7 | -0.9 Millisecond | Standard Deviation 7.71 |
| Healthy Japanese Participants | 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 | QTcF interval, 48 hours, n=7, 7 | 11.6 Millisecond | Standard Deviation 40.64 |
| Healthy Japanese Participants | 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 | QTcF interval, 504 hours, n=7, 6 | 6.7 Millisecond | Standard Deviation 12.84 |
| Healthy Caucasian Participants | 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 | QTcF interval, 24 hours, n=7, 7 | -0.1 Millisecond | Standard Deviation 12.76 |
| Healthy Caucasian Participants | 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 | PR Interval, 4 hours, n=7, 7 | -4.6 Millisecond | Standard Deviation 5.44 |
| Healthy Caucasian Participants | 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 | QT interval, 4 hours, n=7, 7 | -20.4 Millisecond | Standard Deviation 14.28 |
| Healthy Caucasian Participants | 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 | PR Interval, 12 hours, n=7, 7 | -5.9 Millisecond | Standard Deviation 3.89 |
| Healthy Caucasian Participants | 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 | QTcF interval, 4 hours, n=7, 7 | -6.6 Millisecond | Standard Deviation 12.39 |
| Healthy Caucasian Participants | 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 | PR Interval, 24 hours, n=7, 7 | -0.1 Millisecond | Standard Deviation 5.7 |
| Healthy Caucasian Participants | 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 | QT interval, 12 hours, n=7, 7 | -21.7 Millisecond | Standard Deviation 20.09 |
| Healthy Caucasian Participants | 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 | PR Interval, 48 hours, n=7, 7 | 0.3 Millisecond | Standard Deviation 5.41 |
| Healthy Caucasian Participants | 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 | QTcF interval, 504 hours, n=7, 6 | -2.2 Millisecond | Standard Deviation 9.64 |
| Healthy Caucasian Participants | 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 | PR Interval, 504 hours, n=7, 6 | 2.2 Millisecond | Standard Deviation 9.91 |
| Healthy Caucasian Participants | 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 | QT interval, 24 hours, n=7, 7 | -7.3 Millisecond | Standard Deviation 7.48 |
| Healthy Caucasian Participants | 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 | QRS duration, 4 hours, n=7, 7 | -2.1 Millisecond | Standard Deviation 3.24 |
| Healthy Caucasian Participants | 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 | QTcF interval, 12 hours, n=7, 7 | -5.7 Millisecond | Standard Deviation 12.72 |
| Healthy Caucasian Participants | 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 | QRS duration, 12 hours, n=7, 7 | -0.6 Millisecond | Standard Deviation 4.04 |
| Healthy Caucasian Participants | 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 | QT interval, 48 hours, n=7, 7 | -14.7 Millisecond | Standard Deviation 13.5 |
| Healthy Caucasian Participants | 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 | QRS duration, 24 hours, n=7, 7 | -2.0 Millisecond | Standard Deviation 3.96 |
| Healthy Caucasian Participants | 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 | QTcF interval, 48 hours, n=7, 7 | -2.9 Millisecond | Standard Deviation 12.88 |
| Healthy Caucasian Participants | 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 | QRS duration, 48 hours, n=7, 7 | 0.4 Millisecond | Standard Deviation 7.91 |
| Healthy Caucasian Participants | 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 | QT interval, 504 hours, n=7, 6 | -9.2 Millisecond | Standard Deviation 22.93 |
| Healthy Caucasian Participants | 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 | QRS duration, 504 hours, n=7, 6 | -0.8 Millisecond | Standard Deviation 8.08 |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | CL/F of Pyrimethamine in Healthy Caucasian Male Participants | 1114.4 Milliliters per hour | Geometric Coefficient of Variation 27 |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | Cmax of Pyrimethamine in Healthy Caucasian Male Participants | 371.1 Nanogram per milliliter | Geometric Coefficient of Variation 10 |
Secondary
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)
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Ketones, 336 hours, ++ | 2 Participants |
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Ketones, 336 hours, trace | 0 Participants |
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Ketones, follow up (504 hours), + | 1 Participants |
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Occult blood, 336 hours, + | 1 Participants |
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Occult blood, follow up, trace | 0 Participants |
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, Day -1, trace | 0 Participants |
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, 24 hours, trace | 2 Participants |
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, 96 hours, trace | 2 Participants |
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, 168 hours, trace | 2 Participants |
| Healthy Japanese Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, 336 hours, trace | 3 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, 96 hours, trace | 4 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Ketones, 336 hours, ++ | 0 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, Day -1, trace | 1 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Ketones, 336 hours, trace | 1 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, 336 hours, trace | 3 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Ketones, follow up (504 hours), + | 0 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, 24 hours, trace | 3 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Occult blood, 336 hours, + | 0 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Protein, 168 hours, trace | 1 Participants |
| Healthy Caucasian Participants | Number of Participants With Abnormal Urinalysis Parameter | Occult blood, follow up, trace | 1 Participants |
Secondary
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
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Healthy Japanese Participants | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AEs | 2 Participants |
| Healthy Japanese Participants | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAEs | 0 Participants |
| Healthy Caucasian Participants | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any AEs | 6 Participants |
| Healthy Caucasian Participants | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | Any SAEs | 0 Participants |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Specific Gravity at Indicated Time Points | 24 hours, n=7, 7 | 1.0214 Ratio | Standard Deviation 0.00621 |
| Healthy Japanese Participants | Specific Gravity at Indicated Time Points | 168 hours, n=7, 7 | 1.0211 Ratio | Standard Deviation 0.00821 |
| Healthy Japanese Participants | Specific Gravity at Indicated Time Points | Day -1, n=7, 7 | 1.0127 Ratio | Standard Deviation 0.00856 |
| Healthy Japanese Participants | Specific Gravity at Indicated Time Points | 96 hours, n=7, 7 | 1.0211 Ratio | Standard Deviation 0.00832 |
| Healthy Japanese Participants | Specific Gravity at Indicated Time Points | Follow up (504 hours), n=7, 6 | 1.0183 Ratio | Standard Deviation 0.0072 |
| Healthy Japanese Participants | Specific Gravity at Indicated Time Points | 336 hours, n=7, 7 | 1.0193 Ratio | Standard Deviation 0.00871 |
| Healthy Caucasian Participants | Specific Gravity at Indicated Time Points | Follow up (504 hours), n=7, 6 | 1.0222 Ratio | Standard Deviation 0.00728 |
| Healthy Caucasian Participants | Specific Gravity at Indicated Time Points | Day -1, n=7, 7 | 1.0177 Ratio | Standard Deviation 0.0072 |
| Healthy Caucasian Participants | Specific Gravity at Indicated Time Points | 24 hours, n=7, 7 | 1.0256 Ratio | Standard Deviation 0.00665 |
| Healthy Caucasian Participants | Specific Gravity at Indicated Time Points | 96 hours, n=7, 7 | 1.0236 Ratio | Standard Deviation 0.0055 |
| Healthy Caucasian Participants | Specific Gravity at Indicated Time Points | 168 hours, n=7, 7 | 1.0207 Ratio | Standard Deviation 0.00562 |
| Healthy Caucasian Participants | Specific Gravity at Indicated Time Points | 336 hours, n=7, 7 | 1.0246 Ratio | Standard Deviation 0.00945 |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | T1/2 of Pyrimethamine in Healthy Caucasian Male Participants | 99.46 Hours | Standard Deviation 20.745 |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Healthy Japanese Participants | Tmax of Pyrimethamine in Healthy Caucasian Male Participants | 1.000 Hours |
Secondary
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)
Population: Safety Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Japanese Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, n=7, 7 | 6.21 pH | Standard Deviation 0.699 |
| Healthy Japanese Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | 24 hours, n=7, 7 | 5.86 pH | Standard Deviation 0.244 |
| Healthy Japanese Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | 96 hours, n=7, 7 | 5.79 pH | Standard Deviation 0.393 |
| Healthy Japanese Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | 168 hours, n=7, 7 | 5.93 pH | Standard Deviation 0.535 |
| Healthy Japanese Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | 336 hours, n=7, 7 | 6.00 pH | Standard Deviation 0.577 |
| Healthy Japanese Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | Follow up (504 hours), n=7, 6 | 6.43 pH | Standard Deviation 0.673 |
| Healthy Caucasian Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | 336 hours, n=7, 7 | 6.00 pH | Standard Deviation 0.408 |
| Healthy Caucasian Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | Day -1, n=7, 7 | 6.86 pH | Standard Deviation 1.144 |
| Healthy Caucasian Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | 168 hours, n=7, 7 | 6.07 pH | Standard Deviation 0.45 |
| Healthy Caucasian Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | 24 hours, n=7, 7 | 5.79 pH | Standard Deviation 0.567 |
| Healthy Caucasian Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | Follow up (504 hours), n=7, 6 | 6.08 pH | Standard Deviation 0.492 |
| Healthy Caucasian Participants | Urine Potential of Hydrogen (pH) at Indicated Time Points | 96 hours, n=7, 7 | 6.07 pH | Standard Deviation 0.345 |
Secondary
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
Population: Pharmacokinetic Population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Healthy Japanese Participants | Vd/F of Pyrimethamine in Healthy Caucasian Male Participants | 157125.8 Milliliters | Geometric Coefficient of Variation 16.8 |