Trial Outcomes & Findings for Study to Assess the Incidence of Hemolysis, Safety, and Efficacy of Tafenoquine (SB-252263, WR238605) Versus Primaquine in Subjects With Plasmodium Vivax Malaria (NCT NCT02216123)

Last Updated: 2018-05-16

Results Overview

Clinically relevant hemolysis is defined as a decrease in hemoglobin of \>=30% or \>3 grams per deciliter (g/dL) from Baseline; or, an overall drop in hemoglobin below 6.0 g/dL at any visit after the first dose of study medication. The percentage of participants with clinically relevant hemolysis has been summarized. Safety Population comprised of all randomized participants who received at least one dose of blinded study medication.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

251 participants

Primary outcome timeframe

Up to Day 180

Results posted on

2018-05-16

Participant Flow

This is a randomized, double-blind, double-dummy, comparative, multicenter study to assess the incidence of hemolysis, safety and efficacy of Tafenoquine (TQ) versus Primaquine (PQ) in treatment of participants with Plasmodium vivax (P. vivax) malaria.

A total of 369 participants were screened of which 118 failed screening and 251 participants were randomized to receive either TQ+chloroquine (CQ) or PQ+CQ in a ratio of 2:1.

Participant milestones

Participant milestones
Measure	TQ+CQ Participants were administered CQ 600 milligram (mg) once daily on Days 1 and 2 and CQ 300 mg on Day 3. A single dose of TQ 300 mg was administered orally on Day 1 or Day 2. PQ placebo capsules were administered orally once daily for 14 days starting on the same day as TQ administration.	PQ+CQ Participants were administered CQ 600 mg tablet once daily on Days 1 and 2 and CQ 300 mg on Day 3. Participants received a single TQ placebo tablet orally on Day 1 or Day 2. PQ 15 mg was administered orally once daily for 14 days starting on the same day as TQ placebo administration.
Overall Study STARTED	166	85
Overall Study COMPLETED	160	83
Overall Study NOT COMPLETED	6	2

Reasons for withdrawal

Reasons for withdrawal
Measure	TQ+CQ Participants were administered CQ 600 milligram (mg) once daily on Days 1 and 2 and CQ 300 mg on Day 3. A single dose of TQ 300 mg was administered orally on Day 1 or Day 2. PQ placebo capsules were administered orally once daily for 14 days starting on the same day as TQ administration.	PQ+CQ Participants were administered CQ 600 mg tablet once daily on Days 1 and 2 and CQ 300 mg on Day 3. Participants received a single TQ placebo tablet orally on Day 1 or Day 2. PQ 15 mg was administered orally once daily for 14 days starting on the same day as TQ placebo administration.
Overall Study Lost to Follow-up	4	2
Overall Study Withdrawal by Subject	2	0

Baseline Characteristics

Study to Assess the Incidence of Hemolysis, Safety, and Efficacy of Tafenoquine (SB-252263, WR238605) Versus Primaquine in Subjects With Plasmodium Vivax Malaria

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TQ+CQ n=166 Participants Participants were administered CQ 600 milligram (mg) once daily on Days 1 and 2 and CQ 300 mg on Day 3. A single dose of TQ 300 mg was administered orally on Day 1 or Day 2. PQ placebo capsules were administered orally once daily for 14 days starting on the same day as TQ administration.	PQ+CQ n=85 Participants Participants were administered CQ 600 mg tablet once daily on Days 1 and 2 and CQ 300 mg on Day 3. Participants received a single TQ placebo tablet orally on Day 1 or Day 2. PQ 15 mg was administered orally once daily for 14 days starting on the same day as TQ placebo administration.	Total n=251 Participants Total of all reporting groups
Age, Continuous	37.5 Years STANDARD_DEVIATION 14.28 • n=5 Participants	37.7 Years STANDARD_DEVIATION 14.69 • n=7 Participants	37.6 Years STANDARD_DEVIATION 14.39 • n=5 Participants
Sex: Female, Male Female	52 Participants n=5 Participants	32 Participants n=7 Participants	84 Participants n=5 Participants
Sex: Female, Male Male	114 Participants n=5 Participants	53 Participants n=7 Participants	167 Participants n=5 Participants
Race/Ethnicity, Customized American (Amer) Indian (Ind) or Alaska Native (N)	87 Count of Participants n=5 Participants	43 Count of Participants n=7 Participants	130 Count of Participants n=5 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	6 Count of Participants n=5 Participants	3 Count of Participants n=7 Participants	9 Count of Participants n=5 Participants
Race/Ethnicity, Customized Asian-South East Asian Heritage	35 Count of Participants n=5 Participants	20 Count of Participants n=7 Participants	55 Count of Participants n=5 Participants
Race/Ethnicity, Customized Black or African Amer	2 Count of Participants n=5 Participants	0 Count of Participants n=7 Participants	2 Count of Participants n=5 Participants
Race/Ethnicity, Customized African Amer/African Heritage/Amer Ind or Alaska N	36 Count of Participants n=5 Participants	19 Count of Participants n=7 Participants	55 Count of Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 180

Population: Safety Population

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Percentage of Participants With Clinically Relevant Hemolysis.	2.41 Percentage of participants Interval 0.941 to 6.031	1.18 Percentage of participants Interval 0.208 to 6.367

PRIMARY outcome

Timeframe: Up to Day 180

Population: Safety Population

Clinically relevant hemolysis is defined as a decrease in hemoglobin of \>=30% or \>3 g/dL from Baseline; or, an overall drop in hemoglobin below 6.0 g/dL at any visit after the first dose of study medication. Despite additional efforts, no females with moderate G6PD-deficiency were enrolled that experienced clinically-significant hemolysis during the study; hence, the end point could not be estimated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 months post dose

Population: Microbiologic-Intent-To-Treat (mITT) Population comprised of all randomized participants who received at least one dose of blinded study medication and had microscopically-confimed P. vivax parasitemia at Baseline.

A participant was considered to have demonstrated relapse-free efficacy at 6 months if: a) Participant had non-zero P. vivax asexual parasite count at Baseline. b) Participant showed initial clearance of P. vivax parasitemia defined as two negative asexual P. vivax parasite counts, with at least 6 hours between the counts, and no positive counts in the interval. c) Participant had no positive asexual P. vivax parasite count at any assessment prior to or on Study Day 201 following initial parasite clearance. d) Participant did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment. e) Participant is parasite-free at 6 months. The rate of relapse-free efficacy was estimated by Kaplan-Meier methodology. The percentage of participants who were relapse-free at 6 months post dose has been presented along with 95% confidence interval.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Rate of Relapse-free Efficacy at Six Months Post Dose	72.7 Percentage of participants Interval 64.8 to 79.2	75.1 Percentage of participants Interval 64.2 to 83.2

SECONDARY outcome

Timeframe: 4 months post dose

Population: mITT Population

A participant was considered to have demonstrated recurrence-free efficacy at 4 months if: a) Participant had non-zero P. vivax asexual parasite count at Baseline. b) Participant showed initial clearance of P. vivax parasitemia. c) Participant had no positive asexual P. vivax parasite count at any assessment prior to or on Study Day 130 following initial parasite clearance. d) Participant did not take a concomitant medication with anti-malarial activity at any point between Study Day 1 and their last parasite assessment after Study Day 109 (up to and including Study Day 130). e) Participant is parasite-free at 4 months. The rate of relapse-free efficacy was estimated by Kaplan-Meier methodology. The percentage of participants who were relapse-free at 4 months post dose has been presented along with 95% confidence interval.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Rate of Relapse-free Efficacy at Four Months Post Dose	82.3 Percentage of participants Interval 74.9 to 87.7	79.7 Percentage of participants Interval 68.9 to 87.1

SECONDARY outcome

Timeframe: Up to Day 180

Population: mITT Population

Relapse is defined by a positive blood smear with or without vivax symptoms. Relapse is described as any recurrence of malaria that occurred after Day 32 of the study. The time to relapse was analyzed by the Kaplan-Meier method. The median number of days to relapse along with 95% confidence interval has been presented for each treatment group.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Time to Relapse of P. Vivax Malaria	NA Days The median estimate for the time to relapse is the time taken (in days) for 50% of participants to relapse. As less than 50% of participants in both treatment arms relapsed during the study, the median times to relapse could not be calculated.	NA Days The median estimate for the time to relapse is the time taken (in days) for 50% of participants to relapse. As less than 50% of participants in both treatment arms relapsed during the study, the median times to relapse could not be calculated.

SECONDARY outcome

Timeframe: Up to Day 180

Population: mITT Population

Parasite clearance time is defined as time needed to clear asexual parasite from the blood that is, parasite numbers falling below the limit of detection in the thick blood smear and remaining undetectable after 6 to 12 hours later. The time to achieve parasite clearance was analyzed by Kaplan-Meier methodology. The median parasite clearance time along with 95% confidence interval has been presented for each treatment group.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Time to Parasite Clearance	41 Hours Interval 38.0 to 45.0	44 Hours Interval 41.0 to 49.0

SECONDARY outcome

Timeframe: Up to Day 9

Population: mITT Population

Fever clearance time is defined as the time from first dose of treatment to the time when body temperature falls to normal within Study Days 1-4 and remains normal for at least 48 hours up to the Day 8 visit. Fever clearance was considered to have been achieved once an initial temperature of more than 37.4 degree Celsius is reduced to a value less than or equal to 37.4 degree Celsius, in the absence of value more than 37.4 degree Celsius in the following 48 hours up to the Day 8 visit. The time taken to achieve fever clearance was analyzed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Time to Fever Clearance	10 Hours Interval 7.0 to 19.0	13 Hours Interval 8.0 to 22.0

SECONDARY outcome

Timeframe: Up to Day 180

Population: mITT Population

Gametocyte clearance time is defined as time from first dose until the first slide that was gametocyte negative and remained so at the next slide reading. The time taken to achieve gametocyte clearance was analyzed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Time to Gametocyte Clearance	38 Hours Interval 37.0 to 43.0	41 Hours Interval 37.0 to 48.0

SECONDARY outcome

Timeframe: Up to Day 32

Population: mITT Population

Recrudescence is defined as any P. vivax parasitemia occurring on or before Day 32 (that is, blood stage treatment failure). A participant was considered to have had a recrudescence if both of the following were true: a) Participant had a positive P. vivax asexual parasite count at Baseline and demonstrated clearance (that is, did not have two negative asexual P. vivax parasite counts, with at least 6 hours between the counts, and no positive counts in the interval). b) Participant had a positive genetically homologous asexual P. vivax parasite count, after their zero count in Days 1 to 5, but on or before Study Day 32. The number of participants with recrudescence before Study Day 33 has been presented.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Recrudescence	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to Day 180

Population: mITT Population. Only those participants who had a recurrence of infection were included in the analysis.

Two drops of peripheral blood were collected onto pre-printed filter paper for subsequent deoxyribonucleic acid (DNA) extraction and polymerase chain reaction (PCR) analysis of Plasmodium species on all participants at screening (Day 1; pre-dose) and; if necessary, at the time of the first recrudescence/relapse or re-infection. PCR of the P. vivax genes, was used to distinguish between genetically homologous and genetically heterologous infection. The number of participants with genetically homologous and genetically heterologous P. vivax infections has been summarized for each treatment group. Only those participants with an infection occuring on or after Study Day 33 were analyzed.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=42 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=20 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Genetically Homologous and Genetically Heterologous P. Vivax Infections Heterologous P. vivax	8 Participants	9 Participants
Number of Participants With Genetically Homologous and Genetically Heterologous P. Vivax Infections Homologous P. vivax	29 Participants	10 Participants
Number of Participants With Genetically Homologous and Genetically Heterologous P. Vivax Infections Unknown genetic classification	5 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Day 120

Population: Safety Population

Plasma or serum samples were anlalyzed to evaluate clinical chemistry parameters such as alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), bilirubin, creatine kinase, creatinine, glomerular filtration rate (GFR), indirect bilirubin and urea. The number of participants with clinical chemistry laboratory values outside the extended normal range (F3) has been presented. The upper and lower limits for F3 range were defined by multiplying the normal range limits by different factors. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment. Safety Population consisted of all randomized participants who received at least one dose of blinded study medication.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range ALT, High	8 Participants	0 Participants
Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range ALP, High	0 Participants	1 Participants
Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range AST, High	6 Participants	3 Participants
Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range Bilirubin, High	28 Participants	18 Participants
Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range Creatine kinase, High	3 Participants	4 Participants
Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range Creatinine, High	0 Participants	0 Participants
Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range GFR, Low	0 Participants	0 Participants
Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range Indirect bilirubin, High	36 Participants	21 Participants
Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range Urea, High	40 Participants	19 Participants

SECONDARY outcome

Timeframe: Up to Day 120

Population: Safety Population

Blood samples were collected for the evaluation of hematology parameters including eosinophils, leukocytes, lymphocytes, neutrophils, platelets, reticulocytes and methemoglobin. The number of participants with hematology laboratory data outside the extended normal range (F3) has been presented. The upper and lower limits for F3 range were defined by multiplying the normal range limits by different factors. High and low indicated that the participants had values flagged as high and low respectively for the particular parameter any time on-treatment. Participants having both High and Low values for Normal Ranges at any post-baseline visits for safety parameters were counted in both the High and Low categories.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Hematology Laboratory Data Outside the Reference Range Blood eosinophils, High	32 Participants	15 Participants
Number of Participants With Hematology Laboratory Data Outside the Reference Range Blood leukocytes, Low	0 Participants	0 Participants
Number of Participants With Hematology Laboratory Data Outside the Reference Range Blood lymphocytes, Low	8 Participants	1 Participants
Number of Participants With Hematology Laboratory Data Outside the Reference Range Blood lymphocytes, High	11 Participants	4 Participants
Number of Participants With Hematology Laboratory Data Outside the Reference Range Blood neutrophils, Low	5 Participants	3 Participants
Number of Participants With Hematology Laboratory Data Outside the Reference Range Blood platelets, Low	13 Participants	8 Participants
Number of Participants With Hematology Laboratory Data Outside the Reference Range Blood reticulocytes, High	80 Participants	39 Participants
Number of Participants With Hematology Laboratory Data Outside the Reference Range Methemoglobin, High	2 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to Day 120

Population: Safety Population

Mid-stream urine was collected and analyzed for bilirubin, glucose, ketones, leukocyte esterase (LE), nitrites, occult blood, proteins and urobilinogen by dipstick method. The number of participants with abnormal urinalysis results (Trace, +, ++, +++, ++++) has been presented. Only those participants with data available at the specified data points were analyzed.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 60, Trace	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 60, +	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 90, +	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 120, +	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 1, +	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 1, ++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day1, +++	2 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day1, ++++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 3, +	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 3, ++	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 3, +++	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 3, ++++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 5, ++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 5, +++	0 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 1, Trace	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 1, +	9 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day1, ++	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 3, +	8 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 3, ++	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 5, Trace	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 5, +	4 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 8, +	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 11, Trace	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 22, Trace	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Bilirubin, Day 22, +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 8, +	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 8, ++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 8,+++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 11, Trace	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 11, +	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 11, ++	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 11, +++	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 15, ++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 15, +++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 15, ++++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 22, +	1 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 22, +++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 29, Trace	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 29, ++	1 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 60, +	0 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 60, ++	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 90, +	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 90, ++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 90, +++	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 120, Trace	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 120, +	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 120, ++	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 120, +++	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Glucose, Day 120, ++++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 1, Trace	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 1, +	4 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day1, ++	4 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day1, +++	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 3, Trace	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 3, +	5 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 3, ++	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 3, +++	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 5, +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 8, +	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 11, Trace	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 22, Trace	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 22, +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 90, Trace	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 90, +	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 90, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 120, Trace	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 120, +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Ketones, Day 120, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 1, Trace	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 1, +	19 Participants	9 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day1, ++	5 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day1, +++	1 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 3, Trace	4 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 3, +	13 Participants	5 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 3, ++	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 3, +++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 5, Trace	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 5, +	11 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 5, ++	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 5, +++	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 8, Trace	7 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 8, +	10 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 8, ++	6 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 8, +++	2 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 11, Trace	6 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 11, +	11 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 11, ++	3 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 11, +++	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 15, Trace	8 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 15, +	4 Participants	8 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 15, ++	4 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 15, +++	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 22, Trace	4 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 22, +	13 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 22, ++	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 22, +++	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 29, Trace	5 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 29, +	11 Participants	6 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 29, ++	1 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 29, +++	4 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 60, Trace	8 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 60, +	8 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 60, ++	5 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 60, +++	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 90, Trace	6 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 90, +	13 Participants	7 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 90, ++	2 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 90, +++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 120, Trace	5 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 120, +	12 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 120, ++	5 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results LE, Day 120, +++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 1, Trace	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 1, +	4 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 3, +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 5, +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 5, +++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 8, +++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 11, +	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 15, +	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 22, Trace	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 29, +	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 60, +	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 90, Trace	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 90, +	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 120, +	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Nitrite, Day 120, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 1, Trace	2 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 1, +	18 Participants	7 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 1, ++	9 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day1, +++	12 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day1, ++++	6 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 3, Trace	4 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 3, +	14 Participants	6 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 3, ++	9 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 3, +++	5 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 3, ++++	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 5, Trace	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 5, +	7 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 5, ++	6 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 5, +++	4 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 5, ++++	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 8, Trace	4 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 8, +	12 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 8, ++	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 8,+++	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 11, Trace	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 11, +	8 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 11, ++	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 11, +++	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 11, ++++	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 15, Trace	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 15, +	11 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 15, ++	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 15, +++	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 15, ++++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 22, Trace	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 22, +	11 Participants	5 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 22, ++	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 22, +++	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 22, ++++	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 29, Trace	5 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 29, +	17 Participants	5 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 29, ++	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 29, +++	3 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 29, ++++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 60, Trace	5 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 60, +	15 Participants	7 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 60, ++	2 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 60, +++	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 60, ++++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 90, Trace	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 90, +	13 Participants	7 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 90, ++	7 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 90, +++	4 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 90, ++++	2 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 120, Trace	2 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 120, +	13 Participants	5 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 120, ++	3 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 120, +++	6 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Occult blood, Day 120, ++++	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 1, Trace	15 Participants	8 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 1, +	19 Participants	8 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day1, ++	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 3, Trace	8 Participants	6 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 3, +	21 Participants	13 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 3, ++	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 5, Trace	5 Participants	5 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 5, +	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 5, ++	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 8, Trace	6 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 8, +	6 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 8,++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 11, Trace	1 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 11, +	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 11, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 15, +	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 15, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 22, Trace	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 22, +	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 22, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 29, Trace	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 29, +	4 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 29, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 60, Trace	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 60, +	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 60, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 90, Trace	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein Day 90, +	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 120, Trace	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 120, +	6 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Protein, Day 120, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 1, Trace	8 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 1, +	23 Participants	5 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day1, ++	10 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day1, +++	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 3, Trace	6 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 3, +	14 Participants	11 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 3, ++	8 Participants	4 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen Day 3, +++	0 Participants	3 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 3, ++++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 5, Trace	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 5, +	3 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 8, Trace	2 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 8, +	0 Participants	2 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 8, ++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 8,+++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 11, Trace	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 11, +	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 11, ++	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 15, Trace	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 15, +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 15, ++	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 22, Trace	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 29, Trace	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 29, +	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 60, Trace	3 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 60, +	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 90, Trace	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 90, +	3 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 120, Trace	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 120, +	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Dipstick Results Urobilinogen, Day 120, ++	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Day 180

Population: Safety Population

An adverse event (AE) is defined as any untoward medical occurrence in a participant under clinical investigation, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/ birth defect, other situations such as important medical events and events of possible drug induced liver injury with hyperbilirubinemia. TEAEs are defined as AEs with an onset date and time on or after that of the start of first dose of study medication (including CQ). Number of participants with TEAEs and serious TEAEs have been presented.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs TEAEs	119 Participants	64 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Serious TEAEs	6 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Day 29

Population: Safety Population

12 lead ECG was performed with the participant in a semi-supine position having rested in this position for at least 10 minutes. ECG assessments were performed in triplicate at screening followed by single ECGs 12 hours after the first dose of study medication and at Day 29. The number of participants with abnormal-clinically significant ECG findings have been presented. The 12 Hour Post Randomized Treatment (11.5-12.5 Hours) timepoint included all readings taken between 11.5 and 12.5 hours post randomized treatment. The 12 Hour Post Randomized Treatment (8-72 Hours) timepoint is a sensitivity analysis of the 12 Hour post randomized treatment timepoint, including all readings taken between 8 and 72 hours post randomized treatment. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Electrocardiogram (ECG) Findings 11.5 to 12.5 hours Day 1, Assessment 1; n=143, 75	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Findings 11.5 to 12.5 hours Day 1 Assessment 2; n=6, 6	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Findings 11.5 to 12.5 hours Day 1 Assessment 3; n=5, 5	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Findings 8 to 72 hours Day 1 Assessment 1; n=166, 85	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Findings 8 to 72 hours Day 1 Assessment 2; n=6, 6	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Findings 8 to 72 hours Day 1 Assessment 3; n=5, 5	0 Participants	0 Participants
Number of Participants With Electrocardiogram (ECG) Findings Day 29; n=161, 84	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and up to Day 180

Population: Safety Population

Vital signs were measured twice a day on Days 1 through 3, at least 4 hours apart, and immediately prior to pharmacokinetic (PK) measurements. MAP was calculated as the sum of SBP and two times DBP divided by 3. The mean and standard deviation of SBP, DBP and MAP has been presented. The values presented does not include Day 3 assessments for participant number 570. Baseline value is defined as the latest pre-treatment assessment where treatment is their first dose of study medication (CQ/PQ/TQ/Placebo). Change from Baseline is the value at post dose minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

SECONDARY outcome

Timeframe: Baseline and up to Day 180

Population: Safety Population

Vital signs were measured twice a day on Days 1 through 3, at least 4 hours apart, and immediately prior to PK measurements. The mean and standard deviation of pulse rate has been presented. The values presented does not include Day 3 assessments for participant number 570. Baseline value is defined as the latest pre-treatment assessment where treatment is their first dose of study medication (CQ/PQ/TQ/Placebo). Change from Baseline is the value at post dose minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Change From Baseline in Pulse Rate Day 1 assessment 4; n=161, 84	-10.8 beats per minute Standard Deviation 15.24	-9.3 beats per minute Standard Deviation 15.05
Change From Baseline in Pulse Rate Day 2 assessment 1; n=166, 85	-9.9 beats per minute Standard Deviation 17.06	-9.9 beats per minute Standard Deviation 14.90
Change From Baseline in Pulse Rate Day 2 assessment 4; n=166, 85	-11.9 beats per minute Standard Deviation 15.78	-11.8 beats per minute Standard Deviation 13.74
Change From Baseline in Pulse Rate Day 3 assessment 1; n=166, 83	-15.1 beats per minute Standard Deviation 16.62	-18.2 beats per minute Standard Deviation 16.09
Change From Baseline in Pulse Rate Day 3 assessment 4; n=166, 82	-16.5 beats per minute Standard Deviation 17.16	-17.5 beats per minute Standard Deviation 16.17
Change From Baseline in Pulse Rate Day 8; n=164, 84	-12.7 beats per minute Standard Deviation 16.49	-14.6 beats per minute Standard Deviation 17.91
Change From Baseline in Pulse Rate Day 11; n=163, 84	-13.4 beats per minute Standard Deviation 17.83	-15.5 beats per minute Standard Deviation 17.05
Change From Baseline in Pulse Rate Day15; n=165, 84	-13.5 beats per minute Standard Deviation 17.98	-16.9 beats per minute Standard Deviation 17.77
Change From Baseline in Pulse Rate Day 22; n=164, 84	-14.7 beats per minute Standard Deviation 17.72	-16.8 beats per minute Standard Deviation 17.08
Change From Baseline in Pulse Rate Day 29; n=163, 84	-16.9 beats per minute Standard Deviation 16.85	-17.5 beats per minute Standard Deviation 16.27
Change From Baseline in Pulse Rate Day 60; n=160, 83	-16.7 beats per minute Standard Deviation 17.44	-18.5 beats per minute Standard Deviation 17.51
Change From Baseline in Pulse Rate Day 90; n=160, 82	-16.3 beats per minute Standard Deviation 16.87	-18.6 beats per minute Standard Deviation 17.27
Change From Baseline in Pulse Rate Day 120; n=159, 81	-16.7 beats per minute Standard Deviation 17.82	-19.1 beats per minute Standard Deviation 18.40
Change From Baseline in Pulse Rate Day 150; n=161, 82	-16.8 beats per minute Standard Deviation 16.60	-17.9 beats per minute Standard Deviation 18.32
Change From Baseline in Pulse Rate Day180; n=160, 83	-18.0 beats per minute Standard Deviation 18.51	-18.3 beats per minute Standard Deviation 18.27

SECONDARY outcome

Timeframe: Baseline and up to Day 180

Population: Safety Population

Vital signs were performed twice a day on Days 1 through 3, at least 4 hours apart, and immediately prior to PK measurements. The mean and standard deviation of pulse rate has been presented. The values presented does not include Day 3 assessments for participant number 570. Baseline value is defined as the latest pre-treatment assessment where treatment is their first dose of study medication (CQ/PQ/TQ/Placebo). Change from Baseline is the value at post dose minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Change From Baseline in Temperature Day 1 assessment 4; n=161, 84	-0.6 Celsius Standard Deviation 1.05	-0.5 Celsius Standard Deviation 1.29
Change From Baseline in Temperature Day 2 assessment 1; n=166, 85	-0.6 Celsius Standard Deviation 1.20	-0.6 Celsius Standard Deviation 1.36
Change From Baseline in Temperature Day 2 assessment 4; n=166, 85	-0.6 Celsius Standard Deviation 1.08	-0.6 Celsius Standard Deviation 1.14
Change From Baseline in Temperature Day 3 assessment 1; n=166, 83	-1.0 Celsius Standard Deviation 1.03	-0.9 Celsius Standard Deviation 1.10
Change From Baseline in Temperature Day 3 assessment 4; n=166, 82	-1.0 Celsius Standard Deviation 1.02	-1.0 Celsius Standard Deviation 1.09
Change From Baseline in Temperature Day 8; n=164, 84	-1.0 Celsius Standard Deviation 1.01	-0.9 Celsius Standard Deviation 1.03
Change From Baseline in Temperature Day 11; n=163, 84	-1.0 Celsius Standard Deviation 1.05	-0.9 Celsius Standard Deviation 1.05
Change From Baseline in Temperature Day15; n=165, 84	-0.9 Celsius Standard Deviation 1.00	-1.0 Celsius Standard Deviation 1.03
Change From Baseline in Temperature Day 22; n=164, 84	-1.0 Celsius Standard Deviation 0.99	-1.0 Celsius Standard Deviation 1.03
Change From Baseline in Temperature Day 29; n=163, 84	-1.0 Celsius Standard Deviation 0.97	-1.0 Celsius Standard Deviation 1.02
Change From Baseline in Temperature Day 60; n=160, 83	-1.0 Celsius Standard Deviation 1.03	-1.0 Celsius Standard Deviation 1.05
Change From Baseline in Temperature Day 90; n=160, 82	-1.0 Celsius Standard Deviation 1.10	-1.0 Celsius Standard Deviation 0.96
Change From Baseline in Temperature Day 120; n=159, 81	-1.0 Celsius Standard Deviation 1.05	-0.9 Celsius Standard Deviation 1.00
Change From Baseline in Temperature Day 150; n=161, 82	-1.0 Celsius Standard Deviation 1.04	-1.0 Celsius Standard Deviation 1.04
Change From Baseline in Temperature Day180; n=160, 83	-1.0 Celsius Standard Deviation 1.04	-1.0 Celsius Standard Deviation 0.99

SECONDARY outcome

Timeframe: Up to Day 180

Population: mITT Population

Microscopic blood slides (two thick film and one thin film slide) were prepared and examined for asexual parasite count. The number of participants with positive P. falciparum asexual parasite count post Baseline has been summarized for each treatment arm.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With P. Falciparum	4 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to Day 180

Population: Ophthalmic Safety Population

Ophthalmic assessments were carried out at pre-qualified sites prior to randomization and at Days 29 and 90 and at withdrawal follow-up visit. Assessments were carried out at Day 180 (and up to resolution) if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. The number of participants displaying keratopathy in each eye has been summarized for each visit. The number of participants with new keratopathy at any time post Baseline is also reported. Ophthalmic Safety Population comprised of all participants in the Safety Population who have results from any eye assessments. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=27 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=13 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Keratopathy Any time post Baseline; right eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Keratopathy Any time post Baseline; left eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Keratopathy Baseline; right eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Keratopathy Baseline; left eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Keratopathy Day 1; right eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Keratopathy Day 1; left eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Keratopathy Day 29; right eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Keratopathy Day 29; left eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Keratopathy Day 90; right eye; n=27, 12	0 Participants	0 Participants
Number of Participants With Keratopathy Day 90; left eye; n=27, 12	0 Participants	0 Participants
Number of Participants With Keratopathy Day 180; right eye; n=2, 2	0 Participants	0 Participants
Number of Participants With Keratopathy Day 180; left eye; n=2, 2	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and up to Day 180

Population: Ophthalmic Safety Population

Ophthalmic assessments were carried out at pre-qualified sites prior to randomization and at Days 29 and 90 and at withdrawal. Assessments were carried out at Day 180 if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Change from Baseline is the value at post dose visit minus the Baseline value. Best corrected visual acuity was assessed individually for each eye. Scores were recorded as a ratio. The values were used to derive a logMAR score for statistical analysis where logMAR=-1x log10 (ratio score). The number of participants with change in Best Corrected Visual Acuity Test Scores from Baseline has been presented where possible change is defined as a change from Baseline \>=0.12 to \<0.3 and definite change is defined as a change from Baseline \>=0.3 logMAR score. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=27 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=13 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Maximum change; possible; right eye; n=27, 13	1 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Maximum change; definite; right eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Maximum change; possible; left eye; n=27, 13	2 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Maximum change; definite; left eye; n=27, 13	1 Participants	1 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 29; possible change; right eye; n=27, 13	1 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 29; definite change; right eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 29; possible change; left eye; n=27, 13	2 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 29; definite change; left eye; n=27, 13	0 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 90; possible change; right eye; n=27, 12	0 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 90; definite change; right eye; n=27, 12	0 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 90; possible change; left eye; n=27, 12	2 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 90; definite change; left eye; n=27, 12	1 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 180; possible change; right eye; n=2, 2	0 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 180; definite change; right eye; n=2, 2	0 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 180; possible change; left eye; n=2, 2	0 Participants	0 Participants
Number of Participants With Change in Best Corrected Visual Acuity Test Scores Day 180; definite change; left eye; n=2, 2	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and up to Day 180

Population: Ophthalmic Safety Population

Ophthalmic assessments were carried out at pre-qualified sites prior to randomization and at Days 29 and 90 and at withdrawal follow-up. Assessments were carried out at Day 180 (and up to resolution) if the Day 90 assessments showed abnormalities. The last assessment performed on the day of randomization or earlier was considered Baseline. Change from Baseline was calculated as the value at post dose visit minus the Baseline value. The number of participants with definite retinal change and questionable (ques) retinal change from Baseline has been presented. The number of participants with maximum change post-Baseline (definite when absent or questionable at Baseline) has been presented for either eye. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=27 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=13 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Retinal Changes From Baseline Day 29, Definite change, right eye; n=22, 13	0 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 29, Ques change, right eye; n=22, 13	2 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 29, Definite change, left eye; n=22, 13	0 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 29, Ques change, left eye; n=22, 13	1 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 90, Definite change, right eye; n=24, 11	0 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 90, Ques change, right eye; n=24, 11	2 Participants	1 Participants
Number of Participants With Retinal Changes From Baseline Day 90, Definite change, left eye; n=24, 11	0 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 90, Ques change, left eye; n=24, 11	0 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 180, Definite change, right eye; n=3, 2	0 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 180, Ques change, right eye; n=3, 2	0 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 180, Definite change, left eye; n=3, 2	0 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Day 180, Ques change, left eye; n=3, 2	0 Participants	0 Participants
Number of Participants With Retinal Changes From Baseline Maximum change post-Baseline; either eye; n=27, 13	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline and up to Day 120

Population: Safety Population

Methemoglbin is an oxidized and inactive form of hemoglobin. Methemoglobin assessment was made with the aid of a non-invasive signal extraction pulse CO-Oximeter handheld machine. The change from Baseline in percent methemoglobin by treatment, time and sex has been summarized. The latest pre-treatment assessment where treatment is their first dose of study medication (CQ/PQ/TQ/Placebo) was considered as Baseline value. Change from Baseline is the value at post dose visit minus the Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Change From Baseline in Percent Methemoglobin Day 2, Male, n=114, 53	0.02 Percent change Standard Deviation 0.754	0.02 Percent change Standard Deviation 0.406
Change From Baseline in Percent Methemoglobin Day 2, Female, n=52, 32	-0.16 Percent change Standard Deviation 1.168	-0.06 Percent change Standard Deviation 0.181
Change From Baseline in Percent Methemoglobin Day 3, Male, n=114, 53	0.18 Percent change Standard Deviation 0.762	0.03 Percent change Standard Deviation 0.373
Change From Baseline in Percent Methemoglobin Day 3, Female, n=52, 32	0.08 Percent change Standard Deviation 1.264	0.17 Percent change Standard Deviation 0.663
Change From Baseline in Percent Methemoglobin Day 5, Male, n=113, 53	0.77 Percent change Standard Deviation 1.226	0.89 Percent change Standard Deviation 1.207
Change From Baseline in Percent Methemoglobin Day 5, Female, n=52, 32	0.63 Percent change Standard Deviation 1.354	1.32 Percent change Standard Deviation 1.400
Change From Baseline in Percent Methemoglobin Day 8, Male, n=112, 52	1.22 Percent change Standard Deviation 1.505	2.63 Percent change Standard Deviation 2.881
Change From Baseline in Percent Methemoglobin Day 8, Female, n=52, 32	1.00 Percent change Standard Deviation 1.755	2.81 Percent change Standard Deviation 2.530
Change From Baseline in Percent Methemoglobin Day 11, Male, n=112, 52	1.16 Percent change Standard Deviation 1.446	3.30 Percent change Standard Deviation 3.116
Change From Baseline in Percent Methemoglobin Day 11, Female, n=51, 32	1.04 Percent change Standard Deviation 1.656	3.44 Percent change Standard Deviation 2.651
Change From Baseline in Percent Methemoglobin Day 15, Male, n=113, 52	1.01 Percent change Standard Deviation 1.226	3.26 Percent change Standard Deviation 2.920
Change From Baseline in Percent Methemoglobin Day 15, Female, n=52, 32	0.81 Percent change Standard Deviation 1.474	3.61 Percent change Standard Deviation 2.324
Change From Baseline in Percent Methemoglobin Day 22, Male, n=112, 52	0.61 Percent change Standard Deviation 1.008	1.58 Percent change Standard Deviation 1.692
Change From Baseline in Percent Methemoglobin Day 22, Female, n=52, 32	0.32 Percent change Standard Deviation 1.364	2.30 Percent change Standard Deviation 1.900
Change From Baseline in Percent Methemoglobin Day 29, Male, n=111, 52	0.24 Percent change Standard Deviation 0.714	0.46 Percent change Standard Deviation 0.795
Change From Baseline in Percent Methemoglobin Day 29, Female, n=52, 32	-0.02 Percent change Standard Deviation 1.239	0.84 Percent change Standard Deviation 0.842
Change From Baseline in Percent Methemoglobin Day 60, Male, n=107, 51	0.05 Percent change Standard Deviation 0.583	0.20 Percent change Standard Deviation 1.220
Change From Baseline in Percent Methemoglobin Day 60, Female, n=52, 32	-0.09 Percent change Standard Deviation 1.202	0.14 Percent change Standard Deviation 0.496
Change From Baseline in Percent Methemoglobin Day 120, Male, n=109, 50	0.06 Percent change Standard Deviation 0.389	-0.01 Percent change Standard Deviation 0.328
Change From Baseline in Percent Methemoglobin Day 120, Female, n=50, 31	0.14 Percent change Standard Deviation 1.676	0.04 Percent change Standard Deviation 0.422

SECONDARY outcome

Timeframe: Up to Day 180

Population: Safety Population. Only those participants who experienced a relapse or who had a follow-up visit for a relapse were included in the analysis.

Health outcomes were evaluated based on the total costs spent on treatment, transport, medication and tests. The cost was summarized according to the place at which the participant went to for care (drug shop, trial clinic, other clinic, hospital emergency center, other). The costs associated with a relapse episode of P. vivax malaria has been presented. Participants may be represented in more than one category, so the total number of participants may be less than the number quoted. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=72 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Cost Associated With Relapse Episode of P Vivax Malaria Brazil; enrollment clinic for care; n=19, 17	8.208 US Dollars (USD) Standard Deviation 2.8369	8.032 US Dollars (USD) Standard Deviation 2.2403
Cost Associated With Relapse Episode of P Vivax Malaria Colombia; enrollment clinic for care; n=1,0	42.776 US Dollars (USD) Standard Deviation 0	—
Cost Associated With Relapse Episode of P Vivax Malaria Colombia; attended another clinic; n=1,0	4.194 US Dollars (USD) Standard Deviation 0	—
Cost Associated With Relapse Episode of P Vivax Malaria Colombia; hospital emergency center; n=1,1	16.775 US Dollars (USD) Standard Deviation 0	16.775 US Dollars (USD) Standard Deviation 0
Cost Associated With Relapse Episode of P Vivax Malaria Peru; enrollment clinic for care; n=32, 33	9.244 US Dollars (USD) Standard Deviation 2.8235	8.815 US Dollars (USD) Standard Deviation 1.2803
Cost Associated With Relapse Episode of P Vivax Malaria Peru; attended another clinic; n=8, 30	1.677 US Dollars (USD) Standard Deviation 0.9807	3.959 US Dollars (USD) Standard Deviation 0.8522
Cost Associated With Relapse Episode of P Vivax Malaria Thailand; enrollment clinic for care; n=0, 1	—	1.534 US Dollars (USD) Standard Deviation 0
Cost Associated With Relapse Episode of P Vivax Malaria Vietnam; drug shop for care;n=1, 2	0.702 US Dollars (USD) Standard Deviation 0	2.809 US Dollars (USD) Standard Deviation 2.6483
Cost Associated With Relapse Episode of P Vivax Malaria Vietnam; Other; n=1, 0	1.873 US Dollars (USD) Standard Deviation 0	—
Cost Associated With Relapse Episode of P Vivax Malaria Vietnam; attended another clinic; n=0, 1	—	0.936 US Dollars (USD) Standard Deviation 0
Cost Associated With Relapse Episode of P Vivax Malaria Peru; Other; n=8, 0	0.818 US Dollars (USD) Standard Deviation 0.4284	—

SECONDARY outcome

Timeframe: Up to Day 180

Population: Safety Population

Health outcomes were evaluated based on cost incurred due to clinically relevant hemolysis. The total cost was evaluated based on the amount spent on treatment, transport, medication and test. The costs associated with hemolysis event has been presented. The aim of this outcome measure was to determine the cost to a participant due to an event of hemolysis, regardless of treatment received in the study. It was not expected there would be major cost differences with hemoglobin decrease between the treatment arms. This was pre-specified in the statistical analysis plan.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=1 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Cost Associated With a Hemolysis Event	9.174 USD Standard Deviation 0	—

SECONDARY outcome

Timeframe: Up to Day 180

Population: Safety Population

Health outcomes were evaluated based on the cost of medications purchased. The total medication cost for paracetamol associated with relapse episode of P vivax malaria has been presented. Medications recorded as "Other" and medications without costs are excluded from the analysis. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=9 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=4 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Cost Incurred With Purchase of Medications Associated With Relapse Episode of P. Vivax Malaria Colombia; n=2, 1	2.516 USD Standard Deviation 2.3723	4.194 USD Standard Deviation 0
Cost Incurred With Purchase of Medications Associated With Relapse Episode of P. Vivax Malaria Peru; n=6, 2	0.491 USD Standard Deviation 0.1792	0.327 USD Standard Deviation 0.0000
Cost Incurred With Purchase of Medications Associated With Relapse Episode of P. Vivax Malaria Vietnam; n=1, 1	0.468 USD Standard Deviation 0	2.341 USD Standard Deviation 0

SECONDARY outcome

Timeframe: Up to Day 180

Population: Safety Population

Health outcomes were evaluated based on the cost of medications purchased. The total medication cost associated with hemolysis event has been presented. Medications recorded as "Other" and medications without costs are excluded from the analysis. The aim of this outcome measure was to determine the cost to a participant due to an event of hemolysis, regardless of treatment received in the study. It was not expected there would be major cost differences with hemoglobin decrease between the treatment arms. This was pre-specified in the statistical analysis plan.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=1 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Cost Incurred With Purchase of Medications Associated With Hemolysis Event	0 USD Standard Deviation 0	—

SECONDARY outcome

Timeframe: Up to Day 180

Population: Safety Population

Health outcomes were evaluated based on total time lost by participants or care givers due to an episode of malaria. The number of participants or care givers who had taken off from their normal occupation due to relapse episode of P vivax malaria has been presented by country. Participants may be represented in more than one category, so the total number of participants may be less than the number quoted. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=61 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=61 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Vietnam; Farming; n=4, 4	3 Participants	1 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Brazil; Housework; n=2, 1	0 Participants	0 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Brazil; Farming; n=1, 1	0 Participants	0 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Brazil; Student; n=1, 1	0 Participants	0 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Brazil; Paid employment; n=7, 7	0 Participants	0 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Brazil; Other; n=8, 7	0 Participants	0 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Colombia; Housework; n=1, 0	1 Participants	—
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Colombia; Farming; n=2, 2	0 Participants	0 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Colombia; Paid employment; n=1, 1	1 Participants	1 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Peru; Housework; n=18, 18	14 Participants	15 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Peru, Farming; n=4, 4	4 Participants	4 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Peru; Student; n=3, 3	2 Participants	2 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Peru; Paid employment; n=1, 1	1 Participants	1 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Peru; Other; n=7, 7	7 Participants	6 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Thailand; Farming; n=1, 1	1 Participants	1 Participants
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria Vietnam; Paid employment; n=0, 3	—	2 Participants

SECONDARY outcome

Timeframe: Up to Day 180

Population: Safety Population

Health outcomes were evaluated based on total time lost by participants or care givers due to a hemolysis event. The number of participants or care givers who took days off from work due to a hemolysis event has been presented based on the normal occupation. The aim of this outcome measure was to determine the time taken off by participants due to an event of hemolysis, regardless of treatment received in the study. It was not expected there would be major differences in time taken off by participants with hemoglobin decrease between the treatment arms. This was pre-specified in the statistical analysis plan.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=1 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to a Hemolysis Event	0 Participants	—

SECONDARY outcome

Timeframe: Up to Day 180

Population: Safety Population

Health outcomes were evaluated based on the actions taken by the participants to treat relapse episode of P vivax malaria. The number of participants with the type of action taken to treat relapse episode of P vivax malaria has been presented by country. Participants may be represented in more than one category, so the total number of participants may be less than the number quoted. Only those participants with data available at the specified data points were analyzed (represented by n=X in category title).

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=61 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=61 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Peru; Another clinic; n=33, 33	8 Participants	33 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Peru; Other; n=33, 33	9 Participants	0 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Brazil; Trial clinic; n=19, 17	19 Participants	17 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Brazil; Other; n=19, 17	5 Participants	0 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Colombia; Nothing; n=4, 3	2 Participants	2 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Colombia; Trial clinic; n=4, 3	1 Participants	0 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Colombia; Another clinic; n=4, 3	1 Participants	0 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Colombia; Hospital emergency center; n=4, 3	1 Participants	1 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Peru; Trial clinic; n=33, 33	32 Participants	33 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Thailand; Nothing; n=1, 1	1 Participants	0 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Thailand; Trial Clinic; n=1, 1	0 Participants	1 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Vietnam; Nothing; n=4, 7	1 Participants	5 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Vietnam; Drug Shop; n=4, 7	2 Participants	2 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Vietnam; Other; n=4, 7	1 Participants	0 Participants
Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria Vietnam; Another clinic; n=4, 7	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Day 180

Population: Safety Population

Health outcomes were evaluated based on the actions taken by the participants to treat hemolysis events. The number of participants in Brazil who attended the trial clinic to treat a hemolysis event has been presented. The aim of this outcome measure was to determine the action taken by a participant due to an event of hemolysis, regardless of treatment received in the study. It was not expected there would be major differences in action taken by the participants with hemoglobin decrease between the treatment arms. This was pre-specified in the statistical analysis plan.

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=1 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Number of Participants With Action Taken to Treat a Hemolysis Event	1 Participants	—

SECONDARY outcome

Timeframe: Day 2, Day 3, Day 8, Day 15, Day 29, Day 60 and Day 180

Population: Safety Population

Apparent population oral clearance of TQ

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Oral Clearance (CL/F) of TQ	2.96 Liters per hour Interval 2.87 to 3.05	—

SECONDARY outcome

Timeframe: Day 2, Day 3, Day 8, Day 15, Day 29, Day 60 and Day 180

Population: Safety Population

Apparent population central volume of distribution of TQ

Outcome measures

Outcome measures
Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Volume of Distribution (Vc/F) of TQ	915 Liters Interval 879.0 to 956.0	—

Adverse Events

TQ+CQ

Serious events: 6 serious events

Other events: 97 other events

Deaths: 0 deaths

PQ+CQ

Serious events: 1 serious events

Other events: 50 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	TQ+CQ n=166 participants at risk Participants were administered CQ 600 milligram (mg) once daily on Days 1 and 2 and CQ 300 mg on Day 3. A single dose of TQ 300 mg was administered orally on Day 1 or Day 2. PQ placebo capsules were administered orally once daily for 14 days starting on the same day as TQ administration.	PQ+CQ n=85 participants at risk Participants were administered CQ 600 mg tablet once daily on Days 1 and 2 and CQ 300 mg on Day 3. Participants received a single TQ placebo tablet orally on Day 1 or Day 2. PQ 15 mg was administered orally once daily for 14 days starting on the same day as TQ placebo administration.
Investigations Haemoglobin decreased	2.4% 4/166 • Number of events 4 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	1.2% 1/85 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
General disorders Pyrexia	0.60% 1/166 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/85 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Pneumonia	0.60% 1/166 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	0.00% 0/85 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.

Other adverse events

Other adverse events
Measure	TQ+CQ n=166 participants at risk Participants were administered CQ 600 milligram (mg) once daily on Days 1 and 2 and CQ 300 mg on Day 3. A single dose of TQ 300 mg was administered orally on Day 1 or Day 2. PQ placebo capsules were administered orally once daily for 14 days starting on the same day as TQ administration.	PQ+CQ n=85 participants at risk Participants were administered CQ 600 mg tablet once daily on Days 1 and 2 and CQ 300 mg on Day 3. Participants received a single TQ placebo tablet orally on Day 1 or Day 2. PQ 15 mg was administered orally once daily for 14 days starting on the same day as TQ placebo administration.
Nervous system disorders Dizziness	17.5% 29/166 • Number of events 35 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	18.8% 16/85 • Number of events 22 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Nervous system disorders Headache	16.3% 27/166 • Number of events 34 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	18.8% 16/85 • Number of events 22 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Gastrointestinal disorders Nausea	12.7% 21/166 • Number of events 23 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	8.2% 7/85 • Number of events 12 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Gastrointestinal disorders Vomiting	9.0% 15/166 • Number of events 15 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	9.4% 8/85 • Number of events 8 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	7.2% 12/166 • Number of events 12 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	3.5% 3/85 • Number of events 3 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain upper	6.0% 10/166 • Number of events 13 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	1.2% 1/85 • Number of events 1 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	8.4% 14/166 • Number of events 15 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	5.9% 5/85 • Number of events 5 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Urinary tract infection	5.4% 9/166 • Number of events 11 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	10.6% 9/85 • Number of events 10 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Infections and infestations Pharyngitis	3.0% 5/166 • Number of events 5 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	7.1% 6/85 • Number of events 6 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Skin and subcutaneous tissue disorders Pruritus	12.7% 21/166 • Number of events 23 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	22.4% 19/85 • Number of events 19 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	9.0% 15/166 • Number of events 16 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	12.9% 11/85 • Number of events 13 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	5.4% 9/166 • Number of events 11 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	3.5% 3/85 • Number of events 4 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
General disorders Pyrexia	3.6% 6/166 • Number of events 7 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	7.1% 6/85 • Number of events 7 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.
General disorders Asthenia	3.0% 5/166 • Number of events 5 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.	5.9% 5/85 • Number of events 7 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact (Up to Day 180) Safety Population comprised of all randomized participants who received at least one dose of study medication.

Additional Information

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Phone: 866-435-7343

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.
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Measure	First Malaria Relapse n=166 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.	First Malaria Relapse Follow-up n=85 Participants Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 22; n=164, 84	1.2 millimeter of mercury (mmHg) Standard Deviation 10.00	1.3 millimeter of mercury (mmHg) Standard Deviation 9.25
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 1 assessment 4; n=161, 84	1.2 millimeter of mercury (mmHg) Standard Deviation 10.98	-0.9 millimeter of mercury (mmHg) Standard Deviation 10.73
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 2 assessment 1; n=166, 85	0.4 millimeter of mercury (mmHg) Standard Deviation 11.78	-2.3 millimeter of mercury (mmHg) Standard Deviation 10.91
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 2 assessment 4; n=166, 85	-0.8 millimeter of mercury (mmHg) Standard Deviation 12.21	-2.7 millimeter of mercury (mmHg) Standard Deviation 12.46
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 3 assessment 1; n=166, 83	-0.6 millimeter of mercury (mmHg) Standard Deviation 13.38	-2.1 millimeter of mercury (mmHg) Standard Deviation 11.69
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 3 assessment 4; n=166, 82	-2.7 millimeter of mercury (mmHg) Standard Deviation 12.45	-2.2 millimeter of mercury (mmHg) Standard Deviation 12.66
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 8; n=164, 84	2.2 millimeter of mercury (mmHg) Standard Deviation 12.00	0.8 millimeter of mercury (mmHg) Standard Deviation 12.47
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 11; n=163, 84	1.3 millimeter of mercury (mmHg) Standard Deviation 12.35	1.2 millimeter of mercury (mmHg) Standard Deviation 14.69
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day15; n=165, 84	3.2 millimeter of mercury (mmHg) Standard Deviation 13.81	2.5 millimeter of mercury (mmHg) Standard Deviation 12.64
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 22; n=164, 84	3.3 millimeter of mercury (mmHg) Standard Deviation 13.21	2.9 millimeter of mercury (mmHg) Standard Deviation 12.55
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 29; n=163, 84	2.6 millimeter of mercury (mmHg) Standard Deviation 14.08	4.4 millimeter of mercury (mmHg) Standard Deviation 14.29
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 60; n=160, 83	4.4 millimeter of mercury (mmHg) Standard Deviation 14.10	4.3 millimeter of mercury (mmHg) Standard Deviation 15.95
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 90; n=160, 82	3.8 millimeter of mercury (mmHg) Standard Deviation 14.30	5.3 millimeter of mercury (mmHg) Standard Deviation 14.91
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 120; n=159, 81	3.8 millimeter of mercury (mmHg) Standard Deviation 14.05	3.1 millimeter of mercury (mmHg) Standard Deviation 15.40
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day 150; n=161, 82	4.4 millimeter of mercury (mmHg) Standard Deviation 13.99	4.9 millimeter of mercury (mmHg) Standard Deviation 12.83
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) SBP, Day180; n=160, 83	3.7 millimeter of mercury (mmHg) Standard Deviation 14.21	5.7 millimeter of mercury (mmHg) Standard Deviation 13.64
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 1 assessment 4; n=161, 84	1.1 millimeter of mercury (mmHg) Standard Deviation 7.56	-1.5 millimeter of mercury (mmHg) Standard Deviation 8.07
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 2 assessment 1; n=166, 85	-0.1 millimeter of mercury (mmHg) Standard Deviation 8.67	-2.2 millimeter of mercury (mmHg) Standard Deviation 8.42
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 2 assessment 4; n=166, 85	-0.8 millimeter of mercury (mmHg) Standard Deviation 9.57	-2.6 millimeter of mercury (mmHg) Standard Deviation 8.99
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 3 assessment 1; n=166, 83	-0.2 millimeter of mercury (mmHg) Standard Deviation 10.91	-1.3 millimeter of mercury (mmHg) Standard Deviation 9.28
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 3 assessment 4; n=166, 82	-1.9 millimeter of mercury (mmHg) Standard Deviation 9.69	-1.9 millimeter of mercury (mmHg) Standard Deviation 9.79
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 8; n=164, 84	0.9 millimeter of mercury (mmHg) Standard Deviation 8.93	1.1 millimeter of mercury (mmHg) Standard Deviation 9.99
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 11; n=163, 84	-0.0 millimeter of mercury (mmHg) Standard Deviation 9.42	-0.5 millimeter of mercury (mmHg) Standard Deviation 9.39
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day15; n=165, 84	1.5 millimeter of mercury (mmHg) Standard Deviation 10.91	0.4 millimeter of mercury (mmHg) Standard Deviation 9.74
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 29; n=163, 84	0.9 millimeter of mercury (mmHg) Standard Deviation 10.58	1.5 millimeter of mercury (mmHg) Standard Deviation 10.79
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 60; n=160, 83	3.1 millimeter of mercury (mmHg) Standard Deviation 11.05	1.9 millimeter of mercury (mmHg) Standard Deviation 10.34
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 90; n=160, 82	2.7 millimeter of mercury (mmHg) Standard Deviation 11.60	3.5 millimeter of mercury (mmHg) Standard Deviation 9.32
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 120; n=159, 81	3.3 millimeter of mercury (mmHg) Standard Deviation 10.99	2.4 millimeter of mercury (mmHg) Standard Deviation 10.83
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day 150; n=161, 82	3.2 millimeter of mercury (mmHg) Standard Deviation 11.15	4.1 millimeter of mercury (mmHg) Standard Deviation 10.96
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) DBP, Day180; n=160, 83	2.9 millimeter of mercury (mmHg) Standard Deviation 11.04	3.7 millimeter of mercury (mmHg) Standard Deviation 10.71
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 1 assessment 4; n=161, 84	1.1 millimeter of mercury (mmHg) Standard Deviation 7.45	-1.3 millimeter of mercury (mmHg) Standard Deviation 7.98
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 2 assessment 1; n=166, 85	0.0 millimeter of mercury (mmHg) Standard Deviation 8.68	-2.2 millimeter of mercury (mmHg) Standard Deviation 8.08
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 2 assessment 4; n=166, 85	-0.8 millimeter of mercury (mmHg) Standard Deviation 9.48	-2.6 millimeter of mercury (mmHg) Standard Deviation 9.14
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 3 assessment 1; n=166, 83	-0.3 millimeter of mercury (mmHg) Standard Deviation 10.75	-1.6 millimeter of mercury (mmHg) Standard Deviation 8.98
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 3 assessment 4; n=166, 82	-2.2 millimeter of mercury (mmHg) Standard Deviation 9.76	-2.0 millimeter of mercury (mmHg) Standard Deviation 9.91
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 8; n=164, 84	1.3 millimeter of mercury (mmHg) Standard Deviation 8.98	1.0 millimeter of mercury (mmHg) Standard Deviation 9.76
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 11; n=163, 84	0.4 millimeter of mercury (mmHg) Standard Deviation 9.33	0.1 millimeter of mercury (mmHg) Standard Deviation 9.51
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day15; n=165, 84	2.0 millimeter of mercury (mmHg) Standard Deviation 10.72	1.1 millimeter of mercury (mmHg) Standard Deviation 9.58
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 22; n=164, 84	1.9 millimeter of mercury (mmHg) Standard Deviation 9.94	1.8 millimeter of mercury (mmHg) Standard Deviation 9.06
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 29; n=163, 84	1.5 millimeter of mercury (mmHg) Standard Deviation 10.58	2.4 millimeter of mercury (mmHg) Standard Deviation 10.80
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 60; n=160, 83	3.5 millimeter of mercury (mmHg) Standard Deviation 11.07	2.7 millimeter of mercury (mmHg) Standard Deviation 10.79
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 90; n=160, 82	3.1 millimeter of mercury (mmHg) Standard Deviation 11.34	4.1 millimeter of mercury (mmHg) Standard Deviation 9.76
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 120; n=159, 81	3.5 millimeter of mercury (mmHg) Standard Deviation 10.66	2.6 millimeter of mercury (mmHg) Standard Deviation 10.90
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day 150; n=161, 82	3.6 millimeter of mercury (mmHg) Standard Deviation 10.83	4.4 millimeter of mercury (mmHg) Standard Deviation 10.44
Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) MAP, Day180; n=160, 83	3.2 millimeter of mercury (mmHg) Standard Deviation 10.91	4.4 millimeter of mercury (mmHg) Standard Deviation 9.95