Trial Outcomes & Findings for Phase I Study of Pyrimethamine in Healthy Japanese and Caucasian Subjects (NCT NCT03258762)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

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

Results posted on

2020-03-27

Participant Flow

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.

A total of 14 healthy participants were enrolled in this study.

Participant milestones

Participant milestones
Measure	Healthy Japanese Participants Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 milligram (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 milliliters (mL) of water.	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.
Overall Study STARTED	7	7
Overall Study COMPLETED	7	6
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Healthy Japanese Participants Healthy Japanese male participants received a single oral dose of Pyrimethamine 50 milligram (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 milliliters (mL) of water.	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.
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Phase I Study of Pyrimethamine in Healthy Japanese and Caucasian Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.	Total n=14 Participants Total of all reporting groups
Age, Continuous	29.0 Years STANDARD_DEVIATION 3.27 • n=5 Participants	30.7 Years STANDARD_DEVIATION 6.02 • n=7 Participants	29.9 Years STANDARD_DEVIATION 4.74 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	7 Participants n=7 Participants	14 Participants n=5 Participants
Race/Ethnicity, Customized Asian: Japanese Heritage/East Asian	7 Participants n=5 Participants	0 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian/European heritage	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
Maximum Observed Concentration (Cmax) of Pyrimethamine in Healthy Japanese Male Participants	430.5 Nanogram per milliliter Geometric Coefficient of Variation 13.3	—

PRIMARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
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 outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
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 outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
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 8.0	—

PRIMARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
Terminal Half-life (t1/2) of Pyrimethamine in Healthy Japanese Male Participants	122.75 Hours Geometric Coefficient of Variation 21.499	—

PRIMARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
Time to Maximum Observed Concentration (Tmax) of Pyrimethamine in Healthy Japanese Male Participants	2.000 Hours Interval 1.0 to 6.0	—

PRIMARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
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 outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
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	—

SECONDARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
Cmax of Pyrimethamine in Healthy Caucasian Male Participants	371.1 Nanogram per milliliter Geometric Coefficient of Variation 10.0	—

SECONDARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
AUC (0-t) of Pyrimethamine in Healthy Caucasian Male Participants	41582.0 Hours* nanogram per milliliter Geometric Coefficient of Variation 26.9	—

SECONDARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
AUC (0-inf) of Pyrimethamine in Healthy Caucasian Male Participants	44869.1 Hours* nanogram per milliliter Geometric Coefficient of Variation 27.0	—

SECONDARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
AUC (0-24) of Pyrimethamine in Healthy Caucasian Male Participants	6930.8 Hours* nanogram per milliliter Geometric Coefficient of Variation 19.3	—

SECONDARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
Tmax of Pyrimethamine in Healthy Caucasian Male Participants	1.000 Hours Interval 1.0 to 6.0	—

SECONDARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
T1/2 of Pyrimethamine in Healthy Caucasian Male Participants	99.46 Hours Standard Deviation 20.745	—

SECONDARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
CL/F of Pyrimethamine in Healthy Caucasian Male Participants	1114.4 Milliliters per hour Geometric Coefficient of Variation 27.0	—

SECONDARY outcome

Timeframe: 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

Blood samples were collected at indicated time points. The PK parameters were calculated by non-compartmental analysis.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	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.
Vd/F of Pyrimethamine in Healthy Caucasian Male Participants	157125.8 Milliliters Geometric Coefficient of Variation 16.8	—

SECONDARY outcome

Timeframe: Up to Day 23

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any SAEs	0 Participants	0 Participants
Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) Any AEs	2 Participants	6 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Change From Baseline of Clinical Chemistry Parameters: Protein 336 hours, n=7, 7	-4.4 Gram per liter Standard Deviation 6.29	-2.4 Gram per liter Standard Deviation 1.99
Change From Baseline of Clinical Chemistry Parameters: Protein 24 hours, n=7, 7	-4.9 Gram per liter Standard Deviation 4.06	-2.3 Gram per liter Standard Deviation 4.03
Change From Baseline of Clinical Chemistry Parameters: Protein 96 hours, n=7, 7	-4.6 Gram per liter Standard Deviation 6.80	-2.9 Gram per liter Standard Deviation 1.95
Change From Baseline of Clinical Chemistry Parameters: Protein 168 hours, n=7, 7	-3.6 Gram per liter Standard Deviation 7.32	-4.1 Gram per liter Standard Deviation 2.67
Change From Baseline of Clinical Chemistry Parameters: Protein Follow-up (504 hours), n=7, 6	-5.4 Gram per liter Standard Deviation 4.69	-4.2 Gram per liter Standard Deviation 3.54

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Change From Baseline in Hematology Parameter: Reticulocytes 24 hours, n= 7, 7	-0.0016 Proportion of reticulocytes in blood Standard Deviation 0.00172	0.0003 Proportion of reticulocytes in blood Standard Deviation 0.00125
Change From Baseline in Hematology Parameter: Reticulocytes 96 hours, n=7, 7	0.0017 Proportion of reticulocytes in blood Standard Deviation 0.00544	-0.0006 Proportion of reticulocytes in blood Standard Deviation 0.00162
Change From Baseline in Hematology Parameter: Reticulocytes 168 hours, n=7, 7	0.0013 Proportion of reticulocytes in blood Standard Deviation 0.00577	0.0009 Proportion of reticulocytes in blood Standard Deviation 0.00212
Change From Baseline in Hematology Parameter: Reticulocytes 336 hours, n= 7, 7	-0.0011 Proportion of reticulocytes in blood Standard Deviation 0.00430	0.0003 Proportion of reticulocytes in blood Standard Deviation 0.00335
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	0.0017 Proportion of reticulocytes in blood Standard Deviation 0.00308

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
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	0.007 Proportion of red blood cells in blood Standard Deviation 0.0198
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	-0.006 Proportion of red blood cells in blood Standard Deviation 0.0127
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	-0.006 Proportion of red blood cells in blood Standard Deviation 0.0162
Change From Baseline in Hematology Parameter: Hematocrit 336 hours, n= 7, 7	-0.014 Proportion of red blood cells in blood Standard Deviation 0.0190	-0.016 Proportion of red blood cells in blood Standard Deviation 0.0215
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 0.0230	-0.025 Proportion of red blood cells in blood Standard Deviation 0.0152

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Change From Baseline in Hematology Parameter: Hemoglobin 24 hours, n= 7, 7	2.0 Gram per liter Standard Deviation 2.45	3.0 Gram per liter Standard Deviation 5.23
Change From Baseline in Hematology Parameter: Hemoglobin 96 hours, n=7, 7	2.6 Gram per liter Standard Deviation 5.71	0.0 Gram per liter Standard Deviation 2.24
Change From Baseline in Hematology Parameter: Hemoglobin 168 hours, n=7, 7	0.0 Gram per liter Standard Deviation 5.32	-1.7 Gram per liter Standard Deviation 5.50
Change From Baseline in Hematology Parameter: Hemoglobin 336 hours, n= 7, 7	-4.9 Gram per liter Standard Deviation 4.95	-3.6 Gram per liter Standard Deviation 4.54
Change From Baseline in Hematology Parameter: Hemoglobin Follow up (504 hours), n=7, 6	-12.1 Gram per liter Standard Deviation 6.47	-6.0 Gram per liter Standard Deviation 3.22

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin 24 hours, n= 7, 7	0.0 Picogram Standard Deviation 0.00	0.0 Picogram Standard Deviation 0.00
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin 96 hours, n=7, 7	-0.4 Picogram Standard Deviation 0.53	0.0 Picogram Standard Deviation 0.58
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin 168 hours, n=7, 7	0.0 Picogram Standard Deviation 0.82	-0.1 Picogram Standard Deviation 0.69
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin 336 hours, n= 7, 7	0.1 Picogram Standard Deviation 0.90	-0.3 Picogram Standard Deviation 0.76
Change From Baseline in Hematology Parameter: Mean Corpuscular Hemoglobin Follow up (504 hours), n=7, 6	0.0 Picogram Standard Deviation 0.58	-0.2 Picogram Standard Deviation 0.41

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume Follow up (504 hours), n=7, 6	0.4 Femtoliter Standard Deviation 1.27	-1.7 Femtoliter Standard Deviation 1.21
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume 24 hours, n= 7, 7	-0.6 Femtoliter Standard Deviation 0.98	-0.7 Femtoliter Standard Deviation 2.43
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume 96 hours, n=7, 7	0.1 Femtoliter Standard Deviation 0.90	-1.4 Femtoliter Standard Deviation 1.40
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume 168 hours, n=7, 7	-0.3 Femtoliter Standard Deviation 1.11	-1.1 Femtoliter Standard Deviation 1.35
Change From Baseline in Hematology Parameter: Mean Corpuscular Volume 336 hours, n= 7, 7	0.4 Femtoliter Standard Deviation 0.98	-1.9 Femtoliter Standard Deviation 1.68

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Change From Baseline in Hematology Parameter: Erythrocytes 24 hours, n= 7, 7	0.026 10^12 cells per liter Standard Deviation 0.0820	0.100 10^12 cells per liter Standard Deviation 0.1943
Change From Baseline in Hematology Parameter: Erythrocytes 96 hours, n=7, 7	0.101 10^12 cells per liter Standard Deviation 0.1642	0.006 10^12 cells per liter Standard Deviation 0.0680
Change From Baseline in Hematology Parameter: Erythrocytes 168 hours, n=7, 7	-0.024 10^12 cells per liter Standard Deviation 0.2204	-0.021 10^12 cells per liter Standard Deviation 0.1906
Change From Baseline in Hematology Parameter: Erythrocytes 336 hours, n= 7, 7	-0.187 10^12 cells per liter Standard Deviation 0.2051	-0.079 10^12 cells per liter Standard Deviation 0.1901
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	-0.183 10^12 cells per liter Standard Deviation 0.1229

SECONDARY outcome

Timeframe: Day -1, 24, 96, 168, 336 and follow up (504 hours)

Population: Safety Population

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Number of Participants With Abnormal Urinalysis Parameter Ketones, 336 hours, trace	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Parameter Protein, 168 hours, trace	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Parameter Protein, 336 hours, trace	3 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Parameter Ketones, 336 hours, ++	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameter Ketones, follow up (504 hours), +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameter Occult blood, 336 hours, +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Parameter Occult blood, follow up, trace	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Parameter Protein, Day -1, trace	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Parameter Protein, 24 hours, trace	2 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Parameter Protein, 96 hours, trace	2 Participants	4 Participants

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Specific Gravity at Indicated Time Points Day -1, n=7, 7	1.0127 Ratio Standard Deviation 0.00856	1.0177 Ratio Standard Deviation 0.00720
Specific Gravity at Indicated Time Points 24 hours, n=7, 7	1.0214 Ratio Standard Deviation 0.00621	1.0256 Ratio Standard Deviation 0.00665
Specific Gravity at Indicated Time Points 96 hours, n=7, 7	1.0211 Ratio Standard Deviation 0.00832	1.0236 Ratio Standard Deviation 0.00550
Specific Gravity at Indicated Time Points 168 hours, n=7, 7	1.0211 Ratio Standard Deviation 0.00821	1.0207 Ratio Standard Deviation 0.00562
Specific Gravity at Indicated Time Points 336 hours, n=7, 7	1.0193 Ratio Standard Deviation 0.00871	1.0246 Ratio Standard Deviation 0.00945
Specific Gravity at Indicated Time Points Follow up (504 hours), n=7, 6	1.0183 Ratio Standard Deviation 0.00720	1.0222 Ratio Standard Deviation 0.00728

SECONDARY outcome

Timeframe: 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).

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).

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Urine Potential of Hydrogen (pH) at Indicated Time Points Day -1, n=7, 7	6.21 pH Standard Deviation 0.699	6.86 pH Standard Deviation 1.144
Urine Potential of Hydrogen (pH) at Indicated Time Points 24 hours, n=7, 7	5.86 pH Standard Deviation 0.244	5.79 pH Standard Deviation 0.567
Urine Potential of Hydrogen (pH) at Indicated Time Points 96 hours, n=7, 7	5.79 pH Standard Deviation 0.393	6.07 pH Standard Deviation 0.345
Urine Potential of Hydrogen (pH) at Indicated Time Points 168 hours, n=7, 7	5.93 pH Standard Deviation 0.535	6.07 pH Standard Deviation 0.450
Urine Potential of Hydrogen (pH) at Indicated Time Points 336 hours, n=7, 7	6.00 pH Standard Deviation 0.577	6.00 pH Standard Deviation 0.408
Urine Potential of Hydrogen (pH) at Indicated Time Points Follow up (504 hours), n=7, 6	6.43 pH Standard Deviation 0.673	6.08 pH Standard Deviation 0.492

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Change From Baseline in Pulse Rate 336 hours, n=7, 7	1.0 Beats per minute Standard Deviation 17.61	1.6 Beats per minute Standard Deviation 7.50
Change From Baseline in Pulse Rate 504 hours, n=7, 6	-2.1 Beats per minute Standard Deviation 18.52	2.2 Beats per minute Standard Deviation 6.79
Change From Baseline in Pulse Rate 96 hours, n=7, 7	1.4 Beats per minute Standard Deviation 13.44	0.6 Beats per minute Standard Deviation 3.21
Change From Baseline in Pulse Rate 120 hours, n=7, 7	1.1 Beats per minute Standard Deviation 9.58	2.0 Beats per minute Standard Deviation 6.11
Change From Baseline in Pulse Rate 144 hours, n=7, 7	0.1 Beats per minute Standard Deviation 16.74	-0.1 Beats per minute Standard Deviation 3.24
Change From Baseline in Pulse Rate 168 hours, n=7, 7	4.4 Beats per minute Standard Deviation 17.62	7.1 Beats per minute Standard Deviation 7.20
Change From Baseline in Pulse Rate 4 hours, n=7, 7	3.6 Beats per minute Standard Deviation 5.19	4.7 Beats per minute Standard Deviation 6.95
Change From Baseline in Pulse Rate 12 hours, n=7, 7	5.0 Beats per minute Standard Deviation 11.45	10.1 Beats per minute Standard Deviation 6.74
Change From Baseline in Pulse Rate 24 hours, n=7, 7	3.4 Beats per minute Standard Deviation 8.38	-5.0 Beats per minute Standard Deviation 4.36
Change From Baseline in Pulse Rate 48 hours, n=7, 7	3.4 Beats per minute Standard Deviation 18.12	-0.3 Beats per minute Standard Deviation 4.39
Change From Baseline in Pulse Rate 72 hours, n=7, 7	4.9 Beats per minute Standard Deviation 11.26	-0.3 Beats per minute Standard Deviation 4.15

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Change From Baseline in Temperature 4 hours, n=7, 7	-0.01 Celsius Standard Deviation 0.195	0.27 Celsius Standard Deviation 0.095
Change From Baseline in Temperature 12 hours, n=7, 7	0.04 Celsius Standard Deviation 0.172	0.26 Celsius Standard Deviation 0.230
Change From Baseline in Temperature 24 hours, n=7, 7	-0.07 Celsius Standard Deviation 0.150	-0.01 Celsius Standard Deviation 0.241
Change From Baseline in Temperature 48 hours, n=7, 7	-0.16 Celsius Standard Deviation 0.190	-0.04 Celsius Standard Deviation 0.113
Change From Baseline in Temperature 72 hours, n=7, 7	-0.10 Celsius Standard Deviation 0.271	-0.10 Celsius Standard Deviation 0.100
Change From Baseline in Temperature 96 hours, n=7, 7	-0.11 Celsius Standard Deviation 0.212	-0.04 Celsius Standard Deviation 0.098
Change From Baseline in Temperature 120 hours, n=7, 7	-0.10 Celsius Standard Deviation 0.191	-0.17 Celsius Standard Deviation 0.189
Change From Baseline in Temperature 144 hours, n=7, 7	-0.14 Celsius Standard Deviation 0.223	-0.09 Celsius Standard Deviation 0.107
Change From Baseline in Temperature 168 hours, n=7, 7	-0.09 Celsius Standard Deviation 0.186	0.01 Celsius Standard Deviation 0.135
Change From Baseline in Temperature 336 hours, n=7, 7	-0.27 Celsius Standard Deviation 0.315	-0.13 Celsius Standard Deviation 0.170
Change From Baseline in Temperature 504 hours, n=7, 6	-0.26 Celsius Standard Deviation 0.479	-0.07 Celsius Standard Deviation 0.242

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
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	-4.6 Millisecond Standard Deviation 5.44
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	-5.9 Millisecond Standard Deviation 3.89
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	-0.1 Millisecond Standard Deviation 5.70
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 33.80	0.3 Millisecond Standard Deviation 5.41
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	2.2 Millisecond Standard Deviation 9.91
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 1.40	-2.1 Millisecond Standard Deviation 3.24
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	-0.6 Millisecond Standard Deviation 4.04
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 2.50	-2.0 Millisecond Standard Deviation 3.96
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	0.4 Millisecond Standard Deviation 7.91
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	-0.8 Millisecond Standard Deviation 8.08
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	-20.4 Millisecond Standard Deviation 14.28
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	-21.7 Millisecond Standard Deviation 20.09
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	-7.3 Millisecond Standard Deviation 7.48
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	-14.7 Millisecond Standard Deviation 13.50
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	-9.2 Millisecond Standard Deviation 22.93
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	-6.6 Millisecond Standard Deviation 12.39
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	-5.7 Millisecond Standard Deviation 12.72
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	-0.1 Millisecond Standard Deviation 12.76
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	-2.9 Millisecond Standard Deviation 12.88
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	-2.2 Millisecond Standard Deviation 9.64

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Outcome measures
Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
Change From Baseline of ECG Parameter: ECG Mean Heart Rate 504 hours, n=7, 6	-7.1 Beats per minute Standard Deviation 25.71	3.2 Beats per minute Standard Deviation 7.65
Change From Baseline of ECG Parameter: ECG Mean Heart Rate 4 hours, n=7, 7	-2.3 Beats per minute Standard Deviation 11.37	6.0 Beats per minute Standard Deviation 6.32
Change From Baseline of ECG Parameter: ECG Mean Heart Rate 12 hours, n=7, 7	2.3 Beats per minute Standard Deviation 19.91	7.1 Beats per minute Standard Deviation 5.37
Change From Baseline of ECG Parameter: ECG Mean Heart Rate 24 hours, n=7, 7	-5.3 Beats per minute Standard Deviation 19.67	3.1 Beats per minute Standard Deviation 6.72
Change From Baseline of ECG Parameter: ECG Mean Heart Rate 48 hours, n=7, 7	6.7 Beats per minute Standard Deviation 15.64	5.0 Beats per minute Standard Deviation 5.32

Adverse Events

Healthy Japanese Participants

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Healthy Caucasian Participants

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Healthy Japanese Participants n=7 participants at risk 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.	Healthy Caucasian Participants n=7 participants at risk 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.
Infections and infestations Folliculitis	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported
Infections and infestations Upper respiratory tract infection	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported
Infections and infestations Viral infection	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported
Gastrointestinal disorders Abdominal discomfort	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported
Gastrointestinal disorders Nausea	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported
Nervous system disorders Headache	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported
Nervous system disorders Tension headache	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported
General disorders Catheter site pain	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported
Skin and subcutaneous tissue disorders Dry skin	14.3% 1/7 • Number of events 1 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported	0.00% 0/7 • Serious adverse events (SAEs) and non-serious AEs were collected up to Day 23 Non-serious AEs and SAEs for Safety Population was reported

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Publication restrictions are in place

Restriction type: OTHER

Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
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	-0.37 Millimoles per liter Standard Deviation 0.214
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 0.0730	-0.033 Millimoles per liter Standard Deviation 0.0739
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	-0.26 Millimoles per liter Standard Deviation 0.310
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	-0.10 Millimoles per liter Standard Deviation 0.200
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	-0.09 Millimoles per liter Standard Deviation 0.241
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	0.00 Millimoles per liter Standard Deviation 0.276
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	-0.054 Millimoles per liter Standard Deviation 0.0862
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	-0.033 Millimoles per liter Standard Deviation 0.0670
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	-0.040 Millimoles per liter Standard Deviation 0.0432
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	-0.042 Millimoles per liter Standard Deviation 0.0637
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	0.00 Millimoles per liter Standard Deviation 0.580
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	-0.11 Millimoles per liter Standard Deviation 0.515
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	-0.21 Millimoles per liter Standard Deviation 0.241
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	-0.21 Millimoles per liter Standard Deviation 0.515
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	-0.22 Millimoles per liter Standard Deviation 0.488
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	0.0 Millimoles per liter Standard Deviation 2.83
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	1.0 Millimoles per liter Standard Deviation 1.73
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	1.7 Millimoles per liter Standard Deviation 1.25
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	-0.3 Millimoles per liter Standard Deviation 1.38
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	-0.5 Millimoles per liter Standard Deviation 1.76
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	1.01 Millimoles per liter Standard Deviation 1.110
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 1.190	-0.03 Millimoles per liter Standard Deviation 0.660
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	-0.26 Millimoles per liter Standard Deviation 0.885
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	1.06 Millimoles per liter Standard Deviation 1.726
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	1.27 Millimoles per liter Standard Deviation 1.317

Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
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 12.00	-2.9 International units per liter Standard Deviation 5.90
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	-1.9 International units per liter Standard Deviation 4.56
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	-4.3 International units per liter Standard Deviation 6.55
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 11.60	-3.3 International units per liter Standard Deviation 5.71
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	-3.1 International units per liter Standard Deviation 2.97
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	-4.1 International units per liter Standard Deviation 3.48
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	-9.3 International units per liter Standard Deviation 5.89
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	-3.3 International units per liter Standard Deviation 2.81
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	-5.1 International units per liter Standard Deviation 4.91
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	-4.4 International units per liter Standard Deviation 8.16
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	-3.9 International units per liter Standard Deviation 2.79
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	-5.3 International units per liter Standard Deviation 4.59
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	-3.0 International units per liter Standard Deviation 7.62
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	-2.4 International units per liter Standard Deviation 5.86
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	-1.5 International units per liter Standard Deviation 6.83

Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
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 1.50	0.3 Micromoles per liter Standard Deviation 1.97
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	3.1 Micromoles per liter Standard Deviation 4.56
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	2.4 Micromoles per liter Standard Deviation 5.47
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	0.6 Micromoles per liter Standard Deviation 0.53
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	0.7 Micromoles per liter Standard Deviation 1.70
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 2.30	0.9 Micromoles per liter Standard Deviation 1.35
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 1.60	0.9 Micromoles per liter Standard Deviation 1.95
Change From Baseline of Clinical Chemistry Parameters: Direct Bilirubin, Bilirubin, Creatinine. Bilirubin, 168 hours, n=7, 7	0.7 Micromoles per liter Standard Deviation 8.10	1.0 Micromoles per liter Standard Deviation 5.23
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	-0.3 Micromoles per liter Standard Deviation 5.22
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	-1.7 Micromoles per liter Standard Deviation 7.06
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	26.6 Micromoles per liter Standard Deviation 6.68
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	30.1 Micromoles per liter Standard Deviation 7.84
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	24.6 Micromoles per liter Standard Deviation 4.83
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	14.9 Micromoles per liter Standard Deviation 4.71
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	9.5 Micromoles per liter Standard Deviation 7.77

Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
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	0.00 10^9 cells per liter Standard Deviation 0.100
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	0.30 10^9 cells per liter Standard Deviation 0.277
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	0.09 10^9 cells per liter Standard Deviation 0.363
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	0.00 10^9 cells per liter Standard Deviation 0.514
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	0.04 10^9 cells per liter Standard Deviation 0.113
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 0.190	-0.01 10^9 cells per liter Standard Deviation 0.227
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	0.00 10^9 cells per liter Standard Deviation 0.153
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	-0.03 10^9 cells per liter Standard Deviation 0.216
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	-0.54 10^9 cells per liter Standard Deviation 0.702
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	-0.79 10^9 cells per liter Standard Deviation 0.799
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	-0.96 10^9 cells per liter Standard Deviation 0.516
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	-0.97 10^9 cells per liter Standard Deviation 0.612
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	-6.3 10^9 cells per liter Standard Deviation 22.65
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	-13.3 10^9 cells per liter Standard Deviation 38.84
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	-27.3 10^9 cells per liter Standard Deviation 38.70
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	-24.3 10^9 cells per liter Standard Deviation 44.96
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	-0.09 10^9 cells per liter Standard Deviation 0.912
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	-0.46 10^9 cells per liter Standard Deviation 1.149
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	0.07 10^9 cells per liter Standard Deviation 0.058
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 0.150	0.00 10^9 cells per liter Standard Deviation 0.100
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 0.100	0.00 10^9 cells per liter Standard Deviation 0.100
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	-0.05 10^9 cells per liter Standard Deviation 0.071
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	0.36 10^9 cells per liter Standard Deviation 0.251
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	0.26 10^9 cells per liter Standard Deviation 0.276
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	0.00 10^9 cells per liter Standard Deviation 0.115
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	-0.69 10^9 cells per liter Standard Deviation 0.546
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	-11.6 10^9 cells per liter Standard Deviation 27.99
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	-0.36 10^9 cells per liter Standard Deviation 0.735
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	-0.77 10^9 cells per liter Standard Deviation 0.911
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	-0.97 10^9 cells per liter Standard Deviation 1.159

Measure	Healthy Japanese Participants n=7 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.	Healthy Caucasian Participants n=7 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.
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	-0.7 Millimeter of mercury (mmHg) Standard Deviation 6.92
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	-0.3 Millimeter of mercury (mmHg) Standard Deviation 8.60
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	-2.9 Millimeter of mercury (mmHg) Standard Deviation 4.74
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 6.50	2.0 Millimeter of mercury (mmHg) Standard Deviation 2.08
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	-4.6 Millimeter of mercury (mmHg) Standard Deviation 5.13
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	-2.7 Millimeter of mercury (mmHg) Standard Deviation 9.29
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	-3.4 Millimeter of mercury (mmHg) Standard Deviation 11.16
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	-5.4 Millimeter of mercury (mmHg) Standard Deviation 7.32
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	-1.0 Millimeter of mercury (mmHg) Standard Deviation 6.68
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	-5.3 Millimeter of mercury (mmHg) Standard Deviation 4.39
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	-0.7 Millimeter of mercury (mmHg) Standard Deviation 10.01
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	1.3 Millimeter of mercury (mmHg) Standard Deviation 7.04
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	1.0 Millimeter of mercury (mmHg) Standard Deviation 9.73
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	-3.4 Millimeter of mercury (mmHg) Standard Deviation 11.03
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 6.20	-1.1 Millimeter of mercury (mmHg) Standard Deviation 8.55
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	-4.6 Millimeter of mercury (mmHg) Standard Deviation 11.80
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	2.6 Millimeter of mercury (mmHg) Standard Deviation 8.48
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	0.9 Millimeter of mercury (mmHg) Standard Deviation 7.88
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 7.30	-3.3 Millimeter of mercury (mmHg) Standard Deviation 6.52
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	0.9 Millimeter of mercury (mmHg) Standard Deviation 6.67
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	-2.6 Millimeter of mercury (mmHg) Standard Deviation 8.81
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	-1.5 Millimeter of mercury (mmHg) Standard Deviation 5.89