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

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ClinicalTrials.gov Identifier: NCT02216123
Recruitment Status : Completed
First Posted : August 13, 2014
Results First Posted : May 16, 2018
Last Update Posted : May 16, 2018
Sponsor:
Collaborator:
Medicines for Malaria Venture
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Malaria, Vivax
Interventions Drug: Tafenoquine
Drug: Tafenoquine Placebo
Drug: Chloroquine
Drug: Primaquine
Drug: Primaquine Placebo
Enrollment 251
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 166 85
Completed 160 83
Not Completed 6 2
Reason Not Completed
Lost to Follow-up             4             2
Withdrawal by Subject             2             0
Arm/Group Title TQ+CQ PQ+CQ Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 166 85 251
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 166 participants 85 participants 251 participants
37.5  (14.28) 37.7  (14.69) 37.6  (14.39)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 166 participants 85 participants 251 participants
Female
52
  31.3%
32
  37.6%
84
  33.5%
Male
114
  68.7%
53
  62.4%
167
  66.5%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Count of Participants
Number Analyzed 166 participants 85 participants 251 participants
American (Amer) Indian (Ind) or Alaska Native (N) 87 43 130
Asian-East Asian Heritage 6 3 9
Asian-South East Asian Heritage 35 20 55
Black or African Amer 2 0 2
African Amer/African Heritage/Amer Ind or Alaska N 36 19 55
1.Primary Outcome
Title Percentage of Participants With Clinically Relevant Hemolysis.
Hide Description 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.
Time Frame Up to Day 180
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Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
2.41
(0.941 to 6.031)
1.18
(0.208 to 6.367)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TQ+CQ, PQ+CQ
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
-4.161 to 4.982
Estimation Comments Confidence interval for the treatment difference was based on the Newcombe method. Percent treatment difference (TQ+CQ-PQ+CQ) has been presented.
2.Primary Outcome
Title Percentage of Female Participants With Moderate Glucose-6 Phosphate Dehydrogenase (G6PD) Deficiency Experiencing Clinically Relevant Hemolysis.
Hide Description 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.
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Rate of Relapse-free Efficacy at Six Months Post Dose
Hide Description 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.
Time Frame 6 months post dose
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
72.7
(64.8 to 79.2)
75.1
(64.2 to 83.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TQ+CQ, PQ+CQ
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.984
Confidence Interval 95%
0.577 to 1.678
Estimation Comments Hazards ratio was estimated from Cox Proportional Hazards Model with treatment and region as covariates. A hazard ratio <1 indicates a lower chance of relapse with TQ+CQ compared to PQ+CQ.
4.Secondary Outcome
Title Rate of Relapse-free Efficacy at Four Months Post Dose
Hide Description 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.
Time Frame 4 months post dose
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
82.3
(74.9 to 87.7)
79.7
(68.9 to 87.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TQ+CQ, PQ+CQ
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.815
Confidence Interval (2-Sided) 95%
0.442 to 1.503
Estimation Comments Hazard ratio was estimated from Cox Proportional Hazards Model with treatment and region as covariates. A hazard ratio<1 indicates a lower chance of relapse with TQ+CQ compared to PQ+CQ.
5.Secondary Outcome
Title Time to Relapse of P. Vivax Malaria
Hide Description 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.
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
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.
6.Secondary Outcome
Title Time to Parasite Clearance
Hide Description 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.
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Median (95% Confidence Interval)
Unit of Measure: Hours
41
(38 to 45)
44
(41 to 49)
7.Secondary Outcome
Title Time to Fever Clearance
Hide Description 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.
Time Frame Up to Day 9
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Median (95% Confidence Interval)
Unit of Measure: Hours
10
(7 to 19)
13
(8 to 22)
8.Secondary Outcome
Title Time to Gametocyte Clearance
Hide Description 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.
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Median (95% Confidence Interval)
Unit of Measure: Hours
38
(37 to 43)
41
(37 to 48)
9.Secondary Outcome
Title Number of Participants With Recrudescence
Hide Description 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.
Time Frame Up to Day 32
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Unit of Measure: Participants
0 0
10.Secondary Outcome
Title Number of Participants With Genetically Homologous and Genetically Heterologous P. Vivax Infections
Hide Description 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.
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
mITT Population. Only those participants who had a recurrence of infection were included in the analysis.
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 42 20
Measure Type: Number
Unit of Measure: Participants
Heterologous P. vivax 8 9
Homologous P. vivax 29 10
Unknown genetic classification 5 1
11.Secondary Outcome
Title Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range
Hide Description 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.
Time Frame Up to Day 120
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Unit of Measure: Participants
ALT, High 8 0
ALP, High 0 1
AST, High 6 3
Bilirubin, High 28 18
Creatine kinase, High 3 4
Creatinine, High 0 0
GFR, Low 0 0
Indirect bilirubin, High 36 21
Urea, High 40 19
12.Secondary Outcome
Title Number of Participants With Hematology Laboratory Data Outside the Reference Range
Hide Description 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.
Time Frame Up to Day 120
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Unit of Measure: Participants
Blood eosinophils, High 32 15
Blood leukocytes, Low 0 0
Blood lymphocytes, Low 8 1
Blood lymphocytes, High 11 4
Blood neutrophils, Low 5 3
Blood platelets, Low 13 8
Blood reticulocytes, High 80 39
Methemoglobin, High 2 3
13.Secondary Outcome
Title Number of Participants With Abnormal Urinalysis Dipstick Results
Hide Description 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.
Time Frame Up to Day 120
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Unit of Measure: Participants
Bilirubin, Day 1, Trace Number Analyzed 166 participants 84 participants
1 1
Bilirubin, Day 1, + Number Analyzed 166 participants 84 participants
9 2
Bilirubin, Day1, ++ Number Analyzed 166 participants 84 participants
3 0
Bilirubin, Day 3, + Number Analyzed 165 participants 85 participants
8 3
Bilirubin, Day 3, ++ Number Analyzed 165 participants 85 participants
2 0
Bilirubin, Day 5, Trace Number Analyzed 166 participants 85 participants
1 0
Bilirubin, Day 5, + Number Analyzed 166 participants 85 participants
4 0
Bilirubin, Day 8, + Number Analyzed 164 participants 84 participants
0 2
Bilirubin, Day 11, Trace Number Analyzed 163 participants 84 participants
1 1
Bilirubin, Day 22, Trace Number Analyzed 164 participants 84 participants
0 1
Bilirubin, Day 22, + Number Analyzed 164 participants 84 participants
1 0
Bilirubin, Day 60, Trace Number Analyzed 160 participants 83 participants
0 1
Bilirubin, Day 60, + Number Analyzed 160 participants 83 participants
2 1
Bilirubin, Day 90, + Number Analyzed 160 participants 82 participants
0 1
Bilirubin, Day 120, + Number Analyzed 160 participants 81 participants
3 2
Glucose, Day 1, + Number Analyzed 166 participants 84 participants
2 1
Glucose, Day 1, ++ Number Analyzed 166 participants 84 participants
0 1
Glucose, Day1, +++ Number Analyzed 166 participants 84 participants
2 3
Glucose, Day1, ++++ Number Analyzed 166 participants 84 participants
0 1
Glucose, Day 3, + Number Analyzed 165 participants 85 participants
0 1
Glucose, Day 3, ++ Number Analyzed 165 participants 85 participants
1 1
Glucose, Day 3, +++ Number Analyzed 165 participants 85 participants
0 2
Glucose, Day 3, ++++ Number Analyzed 165 participants 85 participants
0 1
Glucose, Day 5, ++ Number Analyzed 166 participants 85 participants
0 1
Glucose, Day 5, +++ Number Analyzed 166 participants 85 participants
0 3
Glucose, Day 8, + Number Analyzed 164 participants 84 participants
1 1
Glucose, Day 8, ++ Number Analyzed 164 participants 84 participants
0 1
Glucose, Day 8,+++ Number Analyzed 164 participants 84 participants
0 1
Glucose, Day 11, Trace Number Analyzed 163 participants 84 participants
0 1
Glucose, Day 11, + Number Analyzed 163 participants 84 participants
0 2
Glucose, Day 11, ++ Number Analyzed 163 participants 84 participants
3 0
Glucose, Day 11, +++ Number Analyzed 163 participants 84 participants
1 1
Glucose, Day 15, ++ Number Analyzed 165 participants 84 participants
0 1
Glucose, Day 15, +++ Number Analyzed 165 participants 84 participants
1 0
Glucose, Day 15, ++++ Number Analyzed 165 participants 84 participants
0 1
Glucose, Day 22, + Number Analyzed 164 participants 84 participants
1 2
Glucose, Day 22, +++ Number Analyzed 164 participants 84 participants
0 1
Glucose, Day 29, Trace Number Analyzed 162 participants 84 participants
1 0
Glucose, Day 29, ++ Number Analyzed 162 participants 84 participants
1 2
Glucose, Day 60, + Number Analyzed 160 participants 83 participants
0 4
Glucose, Day 60, ++ Number Analyzed 160 participants 83 participants
1 1
Glucose, Day 90, + Number Analyzed 160 participants 82 participants
0 1
Glucose, Day 90, ++ Number Analyzed 160 participants 82 participants
0 1
Glucose, Day 90, +++ Number Analyzed 160 participants 82 participants
1 1
Glucose, Day 120, Trace Number Analyzed 160 participants 81 participants
1 0
Glucose, Day 120, + Number Analyzed 160 participants 81 participants
1 1
Glucose, Day 120, ++ Number Analyzed 160 participants 81 participants
0 2
Glucose, Day 120, +++ Number Analyzed 160 participants 81 participants
0 2
Glucose, Day 120, ++++ Number Analyzed 160 participants 81 participants
1 0
Ketones, Day 1, Trace Number Analyzed 166 participants 84 participants
3 0
Ketones, Day 1, + Number Analyzed 166 participants 84 participants
4 2
Ketones, Day1, ++ Number Analyzed 166 participants 84 participants
4 3
Ketones, Day1, +++ Number Analyzed 166 participants 84 participants
2 1
Ketones, Day 3, Trace Number Analyzed 165 participants 85 participants
0 1
Ketones, Day 3, + Number Analyzed 165 participants 85 participants
5 3
Ketones, Day 3, ++ Number Analyzed 165 participants 85 participants
3 2
Ketones, Day 3, +++ Number Analyzed 165 participants 85 participants
3 0
Ketones, Day 5, + Number Analyzed 166 participants 85 participants
1 0
Ketones, Day 8, + Number Analyzed 164 participants 84 participants
1 1
Ketones, Day 11, Trace Number Analyzed 163 participants 84 participants
1 0
Ketones, Day 22, Trace Number Analyzed 164 participants 84 participants
1 1
Ketones, Day 22, + Number Analyzed 164 participants 84 participants
1 0
Ketones, Day 90, Trace Number Analyzed 160 participants 82 participants
2 0
Ketones, Day 90, + Number Analyzed 160 participants 82 participants
0 1
Ketones, Day 90, ++ Number Analyzed 160 participants 82 participants
1 0
Ketones, Day 120, Trace Number Analyzed 160 participants 81 participants
1 0
Ketones, Day 120, + Number Analyzed 160 participants 81 participants
1 0
Ketones, Day 120, ++ Number Analyzed 160 participants 81 participants
1 0
LE, Day 1, Trace Number Analyzed 166 participants 84 participants
3 1
LE, Day 1, + Number Analyzed 166 participants 84 participants
19 9
LE, Day1, ++ Number Analyzed 166 participants 84 participants
5 2
LE, Day1, +++ Number Analyzed 166 participants 84 participants
1 2
LE, Day 3, Trace Number Analyzed 165 participants 85 participants
4 0
LE, Day 3, + Number Analyzed 165 participants 85 participants
13 5
LE, Day 3, ++ Number Analyzed 165 participants 85 participants
2 1
LE, Day 3, +++ Number Analyzed 165 participants 85 participants
1 0
LE, Day 5, Trace Number Analyzed 165 participants 85 participants
3 1
LE, Day 5, + Number Analyzed 165 participants 85 participants
11 4
LE, Day 5, ++ Number Analyzed 165 participants 85 participants
3 2
LE, Day 5, +++ Number Analyzed 165 participants 85 participants
3 2
LE, Day 8, Trace Number Analyzed 164 participants 84 participants
7 3
LE, Day 8, + Number Analyzed 164 participants 84 participants
10 4
LE, Day 8, ++ Number Analyzed 164 participants 84 participants
6 1
LE, Day 8, +++ Number Analyzed 164 participants 84 participants
2 2
LE, Day 11, Trace Number Analyzed 163 participants 84 participants
6 2
LE, Day 11, + Number Analyzed 163 participants 84 participants
11 3
LE, Day 11, ++ Number Analyzed 163 participants 84 participants
3 3
LE, Day 11, +++ Number Analyzed 163 participants 84 participants
3 1
LE, Day 15, Trace Number Analyzed 165 participants 84 participants
8 2
LE, Day 15, + Number Analyzed 165 participants 84 participants
4 8
LE, Day 15, ++ Number Analyzed 165 participants 84 participants
4 3
LE, Day 15, +++ Number Analyzed 165 participants 84 participants
2 1
LE, Day 22, Trace Number Analyzed 164 participants 84 participants
4 2
LE, Day 22, + Number Analyzed 164 participants 84 participants
13 4
LE, Day 22, ++ Number Analyzed 164 participants 84 participants
3 0
LE, Day 22, +++ Number Analyzed 164 participants 84 participants
1 1
LE, Day 29, Trace Number Analyzed 162 participants 84 participants
5 0
LE, Day 29, + Number Analyzed 162 participants 84 participants
11 6
LE, Day 29, ++ Number Analyzed 162 participants 84 participants
1 4
LE, Day 29, +++ Number Analyzed 162 participants 84 participants
4 0
LE, Day 60, Trace Number Analyzed 160 participants 83 participants
8 3
LE, Day 60, + Number Analyzed 160 participants 83 participants
8 4
LE, Day 60, ++ Number Analyzed 160 participants 83 participants
5 2
LE, Day 60, +++ Number Analyzed 160 participants 83 participants
2 1
LE, Day 90, Trace Number Analyzed 159 participants 82 participants
6 1
LE, Day 90, + Number Analyzed 159 participants 82 participants
13 7
LE, Day 90, ++ Number Analyzed 159 participants 82 participants
2 2
LE, Day 90, +++ Number Analyzed 159 participants 82 participants
0 1
LE, Day 120, Trace Number Analyzed 160 participants 81 participants
5 1
LE, Day 120, + Number Analyzed 160 participants 81 participants
12 3
LE, Day 120, ++ Number Analyzed 160 participants 81 participants
5 2
LE, Day 120, +++ Number Analyzed 160 participants 81 participants
0 1
Nitrite, Day 1, Trace Number Analyzed 166 participants 84 participants
1 0
Nitrite, Day 1, + Number Analyzed 166 participants 84 participants
4 0
Nitrite, Day 3, + Number Analyzed 165 participants 85 participants
1 0
Nitrite, Day 5, + Number Analyzed 166 participants 85 participants
1 0
Nitrite, Day 5, +++ Number Analyzed 166 participants 85 participants
1 0
Nitrite, Day 8, +++ Number Analyzed 164 participants 84 participants
1 0
Nitrite, Day 11, + Number Analyzed 163 participants 84 participants
1 1
Nitrite, Day 15, + Number Analyzed 165 participants 84 participants
2 0
Nitrite, Day 22, Trace Number Analyzed 164 participants 84 participants
1 0
Nitrite, Day 29, + Number Analyzed 162 participants 84 participants
2 0
Nitrite, Day 60, + Number Analyzed 160 participants 83 participants
3 0
Nitrite, Day 90, Trace Number Analyzed 160 participants 82 participants
0 1
Nitrite, Day 90, + Number Analyzed 160 participants 82 participants
2 1
Nitrite, Day 120, + Number Analyzed 160 participants 81 participants
2 1
Nitrite, Day 120, ++ Number Analyzed 160 participants 81 participants
1 0
Occult blood, Day 1, Trace Number Analyzed 166 participants 85 participants
2 4
Occult blood, Day 1, + Number Analyzed 166 participants 85 participants
18 7
Occult blood, Day 1, ++ Number Analyzed 166 participants 85 participants
9 4
Occult blood, Day1, +++ Number Analyzed 166 participants 85 participants
12 2
Occult blood, Day1, ++++ Number Analyzed 166 participants 85 participants
6 1
Occult blood, Day 3, Trace Number Analyzed 165 participants 85 participants
4 3
Occult blood, Day 3, + Number Analyzed 165 participants 85 participants
14 6
Occult blood, Day 3, ++ Number Analyzed 165 participants 85 participants
9 3
Occult blood, Day 3, +++ Number Analyzed 165 participants 85 participants
5 3
Occult blood, Day 3, ++++ Number Analyzed 165 participants 85 participants
3 1
Occult blood, Day 5, Trace Number Analyzed 166 participants 85 participants
4 1
Occult blood, Day 5, + Number Analyzed 166 participants 85 participants
7 3
Occult blood, Day 5, ++ Number Analyzed 166 participants 85 participants
6 3
Occult blood, Day 5, +++ Number Analyzed 166 participants 85 participants
4 2
Occult blood, Day 5, ++++ Number Analyzed 166 participants 85 participants
3 2
Occult blood, Day 8, Trace Number Analyzed 164 participants 84 participants
4 4
Occult blood, Day 8, + Number Analyzed 164 participants 84 participants
12 4
Occult blood, Day 8, ++ Number Analyzed 164 participants 84 participants
3 0
Occult blood, Day 8,+++ Number Analyzed 164 participants 84 participants
3 2
Occult blood, Day 11, Trace Number Analyzed 163 participants 84 participants
2 1
Occult blood, Day 11, + Number Analyzed 163 participants 84 participants
8 3
Occult blood, Day 11, ++ Number Analyzed 163 participants 84 participants
3 2
Occult blood, Day 11, +++ Number Analyzed 163 participants 84 participants
3 0
Occult blood, Day 11, ++++ Number Analyzed 163 participants 84 participants
1 1
Occult blood, Day 15, Trace Number Analyzed 165 participants 84 participants
2 1
Occult blood, Day 15, + Number Analyzed 165 participants 84 participants
11 2
Occult blood, Day 15, ++ Number Analyzed 165 participants 84 participants
3 2
Occult blood, Day 15, +++ Number Analyzed 165 participants 84 participants
2 1
Occult blood, Day 15, ++++ Number Analyzed 165 participants 84 participants
0 1
Occult blood, Day 22, Trace Number Analyzed 164 participants 84 participants
4 1
Occult blood, Day 22, + Number Analyzed 164 participants 84 participants
11 5
Occult blood, Day 22, ++ Number Analyzed 164 participants 84 participants
4 1
Occult blood, Day 22, +++ Number Analyzed 164 participants 84 participants
2 1
Occult blood, Day 22, ++++ Number Analyzed 164 participants 84 participants
1 1
Occult blood, Day 29, Trace Number Analyzed 162 participants 84 participants
5 2
Occult blood, Day 29, + Number Analyzed 162 participants 84 participants
17 5
Occult blood, Day 29, ++ Number Analyzed 162 participants 84 participants
3 1
Occult blood, Day 29, +++ Number Analyzed 162 participants 84 participants
3 4
Occult blood, Day 29, ++++ Number Analyzed 162 participants 84 participants
1 0
Occult blood, Day 60, Trace Number Analyzed 160 participants 83 participants
5 0
Occult blood, Day 60, + Number Analyzed 160 participants 83 participants
15 7
Occult blood, Day 60, ++ Number Analyzed 160 participants 83 participants
2 3
Occult blood, Day 60, +++ Number Analyzed 160 participants 83 participants
3 0
Occult blood, Day 60, ++++ Number Analyzed 160 participants 83 participants
1 0
Occult blood, Day 90, Trace Number Analyzed 160 participants 82 participants
4 1
Occult blood, Day 90, + Number Analyzed 160 participants 82 participants
13 7
Occult blood, Day 90, ++ Number Analyzed 160 participants 82 participants
7 2
Occult blood, Day 90, +++ Number Analyzed 160 participants 82 participants
4 3
Occult blood, Day 90, ++++ Number Analyzed 160 participants 82 participants
2 2
Occult blood, Day 120, Trace Number Analyzed 160 participants 81 participants
2 2
Occult blood, Day 120, + Number Analyzed 160 participants 81 participants
13 5
Occult blood, Day 120, ++ Number Analyzed 160 participants 81 participants
3 3
Occult blood, Day 120, +++ Number Analyzed 160 participants 81 participants
6 0
Occult blood, Day 120, ++++ Number Analyzed 160 participants 81 participants
0 2
Protein, Day 1, Trace Number Analyzed 166 participants 85 participants
15 8
Protein, Day 1, + Number Analyzed 166 participants 85 participants
19 8
Protein, Day1, ++ Number Analyzed 166 participants 85 participants
4 1
Protein, Day 3, Trace Number Analyzed 165 participants 85 participants
8 6
Protein, Day 3, + Number Analyzed 165 participants 85 participants
21 13
Protein, Day 3, ++ Number Analyzed 165 participants 85 participants
3 1
Protein, Day 5, Trace Number Analyzed 166 participants 85 participants
5 5
Protein, Day 5, + Number Analyzed 166 participants 85 participants
4 1
Protein, Day 5, ++ Number Analyzed 166 participants 85 participants
2 1
Protein, Day 8, Trace Number Analyzed 164 participants 84 participants
6 4
Protein, Day 8, + Number Analyzed 164 participants 84 participants
6 2
Protein, Day 8,++ Number Analyzed 164 participants 84 participants
1 0
Protein, Day 11, Trace Number Analyzed 163 participants 84 participants
1 3
Protein, Day 11, + Number Analyzed 163 participants 84 participants
4 1
Protein, Day 11, ++ Number Analyzed 163 participants 84 participants
1 0
Protein, Day 15, + Number Analyzed 165 participants 84 participants
2 0
Protein, Day 15, ++ Number Analyzed 165 participants 84 participants
1 0
Protein, Day 22, Trace Number Analyzed 164 participants 84 participants
2 1
Protein, Day 22, + Number Analyzed 164 participants 84 participants
2 1
Protein, Day 22, ++ Number Analyzed 164 participants 84 participants
1 0
Protein, Day 29, Trace Number Analyzed 162 participants 84 participants
3 1
Protein, Day 29, + Number Analyzed 162 participants 84 participants
4 0
Protein, Day 29, ++ Number Analyzed 162 participants 84 participants
1 0
Protein, Day 60, Trace Number Analyzed 160 participants 83 participants
3 1
Protein, Day 60, + Number Analyzed 160 participants 83 participants
3 2
Protein, Day 60, ++ Number Analyzed 160 participants 83 participants
1 0
Protein, Day 90, Trace Number Analyzed 160 participants 82 participants
4 1
Protein Day 90, + Number Analyzed 160 participants 82 participants
3 0
Protein, Day 120, Trace Number Analyzed 160 participants 81 participants
2 1
Protein, Day 120, + Number Analyzed 160 participants 81 participants
6 0
Protein, Day 120, ++ Number Analyzed 160 participants 81 participants
1 0
Urobilinogen, Day 1, Trace Number Analyzed 166 participants 84 participants
8 0
Urobilinogen, Day 1, + Number Analyzed 166 participants 84 participants
23 5
Urobilinogen, Day1, ++ Number Analyzed 166 participants 84 participants
10 4
Urobilinogen, Day1, +++ Number Analyzed 166 participants 84 participants
3 1
Urobilinogen, Day 3, Trace Number Analyzed 165 participants 85 participants
6 2
Urobilinogen, Day 3, + Number Analyzed 165 participants 85 participants
14 11
Urobilinogen, Day 3, ++ Number Analyzed 165 participants 85 participants
8 4
Urobilinogen Day 3, +++ Number Analyzed 165 participants 85 participants
0 3
Urobilinogen, Day 3, ++++ Number Analyzed 165 participants 85 participants
0 1
Urobilinogen, Day 5, Trace Number Analyzed 166 participants 85 participants
3 1
Urobilinogen, Day 5, + Number Analyzed 166 participants 85 participants
3 2
Urobilinogen, Day 8, Trace Number Analyzed 164 participants 84 participants
2 2
Urobilinogen, Day 8, + Number Analyzed 164 participants 84 participants
0 2
Urobilinogen, Day 8, ++ Number Analyzed 164 participants 84 participants
0 1
Urobilinogen, Day 8,+++ Number Analyzed 164 participants 84 participants
0 1
Urobilinogen, Day 11, Trace Number Analyzed 163 participants 84 participants
1 1
Urobilinogen, Day 11, + Number Analyzed 163 participants 84 participants
2 0
Urobilinogen, Day 11, ++ Number Analyzed 163 participants 84 participants
0 1
Urobilinogen, Day 15, Trace Number Analyzed 164 participants 84 participants
3 1
Urobilinogen, Day 15, + Number Analyzed 164 participants 84 participants
1 0
Urobilinogen, Day 15, ++ Number Analyzed 164 participants 84 participants
1 0
Urobilinogen, Day 22, Trace Number Analyzed 164 participants 84 participants
3 0
Urobilinogen, Day 29, Trace Number Analyzed 162 participants 84 participants
4 1
Urobilinogen, Day 29, + Number Analyzed 162 participants 84 participants
2 1
Urobilinogen, Day 60, Trace Number Analyzed 160 participants 83 participants
3 1
Urobilinogen, Day 60, + Number Analyzed 160 participants 83 participants
1 0
Urobilinogen, Day 90, Trace Number Analyzed 160 participants 82 participants
4 1
Urobilinogen, Day 90, + Number Analyzed 160 participants 82 participants
3 0
Urobilinogen, Day 120, Trace Number Analyzed 160 participants 81 participants
2 0
Urobilinogen, Day 120, + Number Analyzed 160 participants 81 participants
2 0
Urobilinogen, Day 120, ++ Number Analyzed 160 participants 81 participants
0 1
14.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
Hide Description 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.
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Unit of Measure: Participants
TEAEs 119 64
Serious TEAEs 6 1
15.Secondary Outcome
Title Number of Participants With Electrocardiogram (ECG) Findings
Hide Description 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).
Time Frame Up to Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Unit of Measure: Participants
11.5 to 12.5 hours Day 1, Assessment 1; n=143, 75 Number Analyzed 143 participants 75 participants
0 0
11.5 to 12.5 hours Day 1 Assessment 2; n=6, 6 Number Analyzed 6 participants 6 participants
0 0
11.5 to 12.5 hours Day 1 Assessment 3; n=5, 5 Number Analyzed 5 participants 5 participants
0 0
8 to 72 hours Day 1 Assessment 1; n=166, 85 Number Analyzed 166 participants 85 participants
0 0
8 to 72 hours Day 1 Assessment 2; n=6, 6 Number Analyzed 6 participants 6 participants
0 0
8 to 72 hours Day 1 Assessment 3; n=5, 5 Number Analyzed 5 participants 5 participants
0 0
Day 29; n=161, 84 Number Analyzed 161 participants 84 participants
0 0
16.Secondary Outcome
Title Change From Baseline in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP)
Hide Description 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).
Time Frame Baseline and up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Mean (Standard Deviation)
Unit of Measure: millimeter of mercury (mmHg)
SBP, Day 1 assessment 4; n=161, 84 Number Analyzed 161 participants 84 participants
1.2  (10.98) -0.9  (10.73)
SBP, Day 2 assessment 1; n=166, 85 Number Analyzed 166 participants 85 participants
0.4  (11.78) -2.3  (10.91)
SBP, Day 2 assessment 4; n=166, 85 Number Analyzed 166 participants 85 participants
-0.8  (12.21) -2.7  (12.46)
SBP, Day 3 assessment 1; n=166, 83 Number Analyzed 166 participants 83 participants
-0.6  (13.38) -2.1  (11.69)
SBP, Day 3 assessment 4; n=166, 82 Number Analyzed 166 participants 82 participants
-2.7  (12.45) -2.2  (12.66)
SBP, Day 8; n=164, 84 Number Analyzed 164 participants 84 participants
2.2  (12.00) 0.8  (12.47)
SBP, Day 11; n=163, 84 Number Analyzed 163 participants 84 participants
1.3  (12.35) 1.2  (14.69)
SBP, Day15; n=165, 84 Number Analyzed 165 participants 84 participants
3.2  (13.81) 2.5  (12.64)
SBP, Day 22; n=164, 84 Number Analyzed 164 participants 84 participants
3.3  (13.21) 2.9  (12.55)
SBP, Day 29; n=163, 84 Number Analyzed 163 participants 84 participants
2.6  (14.08) 4.4  (14.29)
SBP, Day 60; n=160, 83 Number Analyzed 160 participants 83 participants
4.4  (14.10) 4.3  (15.95)
SBP, Day 90; n=160, 82 Number Analyzed 160 participants 82 participants
3.8  (14.30) 5.3  (14.91)
SBP, Day 120; n=159, 81 Number Analyzed 159 participants 81 participants
3.8  (14.05) 3.1  (15.40)
SBP, Day 150; n=161, 82 Number Analyzed 161 participants 82 participants
4.4  (13.99) 4.9  (12.83)
SBP, Day180; n=160, 83 Number Analyzed 160 participants 83 participants
3.7  (14.21) 5.7  (13.64)
DBP, Day 1 assessment 4; n=161, 84 Number Analyzed 161 participants 84 participants
1.1  (7.56) -1.5  (8.07)
DBP, Day 2 assessment 1; n=166, 85 Number Analyzed 166 participants 85 participants
-0.1  (8.67) -2.2  (8.42)
DBP, Day 2 assessment 4; n=166, 85 Number Analyzed 166 participants 85 participants
-0.8  (9.57) -2.6  (8.99)
DBP, Day 3 assessment 1; n=166, 83 Number Analyzed 166 participants 83 participants
-0.2  (10.91) -1.3  (9.28)
DBP, Day 3 assessment 4; n=166, 82 Number Analyzed 166 participants 82 participants
-1.9  (9.69) -1.9  (9.79)
DBP, Day 8; n=164, 84 Number Analyzed 164 participants 84 participants
0.9  (8.93) 1.1  (9.99)
DBP, Day 11; n=163, 84 Number Analyzed 163 participants 84 participants
-0.0  (9.42) -0.5  (9.39)
DBP, Day15; n=165, 84 Number Analyzed 165 participants 84 participants
1.5  (10.91) 0.4  (9.74)
DBP, Day 22; n=164, 84 Number Analyzed 164 participants 84 participants
1.2  (10.00) 1.3  (9.25)
DBP, Day 29; n=163, 84 Number Analyzed 163 participants 84 participants
0.9  (10.58) 1.5  (10.79)
DBP, Day 60; n=160, 83 Number Analyzed 160 participants 83 participants
3.1  (11.05) 1.9  (10.34)
DBP, Day 90; n=160, 82 Number Analyzed 160 participants 82 participants
2.7  (11.60) 3.5  (9.32)
DBP, Day 120; n=159, 81 Number Analyzed 159 participants 81 participants
3.3  (10.99) 2.4  (10.83)
DBP, Day 150; n=161, 82 Number Analyzed 161 participants 82 participants
3.2  (11.15) 4.1  (10.96)
DBP, Day180; n=160, 83 Number Analyzed 160 participants 83 participants
2.9  (11.04) 3.7  (10.71)
MAP, Day 1 assessment 4; n=161, 84 Number Analyzed 161 participants 84 participants
1.1  (7.45) -1.3  (7.98)
MAP, Day 2 assessment 1; n=166, 85 Number Analyzed 166 participants 85 participants
0.0  (8.68) -2.2  (8.08)
MAP, Day 2 assessment 4; n=166, 85 Number Analyzed 166 participants 85 participants
-0.8  (9.48) -2.6  (9.14)
MAP, Day 3 assessment 1; n=166, 83 Number Analyzed 166 participants 83 participants
-0.3  (10.75) -1.6  (8.98)
MAP, Day 3 assessment 4; n=166, 82 Number Analyzed 166 participants 82 participants
-2.2  (9.76) -2.0  (9.91)
MAP, Day 8; n=164, 84 Number Analyzed 164 participants 84 participants
1.3  (8.98) 1.0  (9.76)
MAP, Day 11; n=163, 84 Number Analyzed 163 participants 84 participants
0.4  (9.33) 0.1  (9.51)
MAP, Day15; n=165, 84 Number Analyzed 165 participants 84 participants
2.0  (10.72) 1.1  (9.58)
MAP, Day 22; n=164, 84 Number Analyzed 164 participants 84 participants
1.9  (9.94) 1.8  (9.06)
MAP, Day 29; n=163, 84 Number Analyzed 163 participants 84 participants
1.5  (10.58) 2.4  (10.80)
MAP, Day 60; n=160, 83 Number Analyzed 160 participants 83 participants
3.5  (11.07) 2.7  (10.79)
MAP, Day 90; n=160, 82 Number Analyzed 160 participants 82 participants
3.1  (11.34) 4.1  (9.76)
MAP, Day 120; n=159, 81 Number Analyzed 159 participants 81 participants
3.5  (10.66) 2.6  (10.90)
MAP, Day 150; n=161, 82 Number Analyzed 161 participants 82 participants
3.6  (10.83) 4.4  (10.44)
MAP, Day180; n=160, 83 Number Analyzed 160 participants 83 participants
3.2  (10.91) 4.4  (9.95)
17.Secondary Outcome
Title Change From Baseline in Pulse Rate
Hide Description 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).
Time Frame Baseline and up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Mean (Standard Deviation)
Unit of Measure: beats per minute
Day 1 assessment 4; n=161, 84 Number Analyzed 161 participants 84 participants
-10.8  (15.24) -9.3  (15.05)
Day 2 assessment 1; n=166, 85 Number Analyzed 166 participants 85 participants
-9.9  (17.06) -9.9  (14.90)
Day 2 assessment 4; n=166, 85 Number Analyzed 166 participants 85 participants
-11.9  (15.78) -11.8  (13.74)
Day 3 assessment 1; n=166, 83 Number Analyzed 166 participants 83 participants
-15.1  (16.62) -18.2  (16.09)
Day 3 assessment 4; n=166, 82 Number Analyzed 166 participants 82 participants
-16.5  (17.16) -17.5  (16.17)
Day 8; n=164, 84 Number Analyzed 164 participants 84 participants
-12.7  (16.49) -14.6  (17.91)
Day 11; n=163, 84 Number Analyzed 163 participants 84 participants
-13.4  (17.83) -15.5  (17.05)
Day15; n=165, 84 Number Analyzed 165 participants 84 participants
-13.5  (17.98) -16.9  (17.77)
Day 22; n=164, 84 Number Analyzed 164 participants 84 participants
-14.7  (17.72) -16.8  (17.08)
Day 29; n=163, 84 Number Analyzed 163 participants 84 participants
-16.9  (16.85) -17.5  (16.27)
Day 60; n=160, 83 Number Analyzed 160 participants 83 participants
-16.7  (17.44) -18.5  (17.51)
Day 90; n=160, 82 Number Analyzed 160 participants 82 participants
-16.3  (16.87) -18.6  (17.27)
Day 120; n=159, 81 Number Analyzed 159 participants 81 participants
-16.7  (17.82) -19.1  (18.40)
Day 150; n=161, 82 Number Analyzed 161 participants 82 participants
-16.8  (16.60) -17.9  (18.32)
Day180; n=160, 83 Number Analyzed 160 participants 83 participants
-18.0  (18.51) -18.3  (18.27)
18.Secondary Outcome
Title Change From Baseline in Temperature
Hide Description 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).
Time Frame Baseline and up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Mean (Standard Deviation)
Unit of Measure: Celsius
Day 1 assessment 4; n=161, 84 Number Analyzed 161 participants 84 participants
-0.6  (1.05) -0.5  (1.29)
Day 2 assessment 1; n=166, 85 Number Analyzed 166 participants 85 participants
-0.6  (1.20) -0.6  (1.36)
Day 2 assessment 4; n=166, 85 Number Analyzed 166 participants 85 participants
-0.6  (1.08) -0.6  (1.14)
Day 3 assessment 1; n=166, 83 Number Analyzed 166 participants 83 participants
-1.0  (1.03) -0.9  (1.10)
Day 3 assessment 4; n=166, 82 Number Analyzed 166 participants 82 participants
-1.0  (1.02) -1.0  (1.09)
Day 8; n=164, 84 Number Analyzed 164 participants 84 participants
-1.0  (1.01) -0.9  (1.03)
Day 11; n=163, 84 Number Analyzed 163 participants 84 participants
-1.0  (1.05) -0.9  (1.05)
Day15; n=165, 84 Number Analyzed 165 participants 84 participants
-0.9  (1.00) -1.0  (1.03)
Day 22; n=164, 84 Number Analyzed 164 participants 84 participants
-1.0  (0.99) -1.0  (1.03)
Day 29; n=163, 84 Number Analyzed 163 participants 84 participants
-1.0  (0.97) -1.0  (1.02)
Day 60; n=160, 83 Number Analyzed 160 participants 83 participants
-1.0  (1.03) -1.0  (1.05)
Day 90; n=160, 82 Number Analyzed 160 participants 82 participants
-1.0  (1.10) -1.0  (0.96)
Day 120; n=159, 81 Number Analyzed 159 participants 81 participants
-1.0  (1.05) -0.9  (1.00)
Day 150; n=161, 82 Number Analyzed 161 participants 82 participants
-1.0  (1.04) -1.0  (1.04)
Day180; n=160, 83 Number Analyzed 160 participants 83 participants
-1.0  (1.04) -1.0  (0.99)
19.Secondary Outcome
Title Number of Participants With P. Falciparum
Hide Description 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.
Time Frame Up to Day 180
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Hide Analysis Population Description
mITT Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Measure Type: Number
Unit of Measure: Participants
4 3
20.Secondary Outcome
Title Number of Participants With Keratopathy
Hide Description 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).
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Ophthalmic Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 27 13
Measure Type: Number
Unit of Measure: Participants
Baseline; right eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Baseline; left eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Day 1; right eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Day 1; left eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Day 29; right eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Day 29; left eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Day 90; right eye; n=27, 12 Number Analyzed 27 participants 12 participants
0 0
Day 90; left eye; n=27, 12 Number Analyzed 27 participants 12 participants
0 0
Day 180; right eye; n=2, 2 Number Analyzed 2 participants 2 participants
0 0
Day 180; left eye; n=2, 2 Number Analyzed 2 participants 2 participants
0 0
Any time post Baseline; right eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Any time post Baseline; left eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
21.Secondary Outcome
Title Number of Participants With Change in Best Corrected Visual Acuity Test Scores
Hide Description 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).
Time Frame Baseline and up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Ophthalmic Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 27 13
Measure Type: Number
Unit of Measure: Participants
Maximum change; possible; right eye; n=27, 13 Number Analyzed 27 participants 13 participants
1 0
Maximum change; definite; right eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Maximum change; possible; left eye; n=27, 13 Number Analyzed 27 participants 13 participants
2 0
Maximum change; definite; left eye; n=27, 13 Number Analyzed 27 participants 13 participants
1 1
Day 29; possible change; right eye; n=27, 13 Number Analyzed 27 participants 13 participants
1 0
Day 29; definite change; right eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Day 29; possible change; left eye; n=27, 13 Number Analyzed 27 participants 13 participants
2 0
Day 29; definite change; left eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
Day 90; possible change; right eye; n=27, 12 Number Analyzed 27 participants 12 participants
0 0
Day 90; definite change; right eye; n=27, 12 Number Analyzed 27 participants 12 participants
0 0
Day 90; possible change; left eye; n=27, 12 Number Analyzed 27 participants 12 participants
2 0
Day 90; definite change; left eye; n=27, 12 Number Analyzed 27 participants 12 participants
1 0
Day 180; possible change; right eye; n=2, 2 Number Analyzed 2 participants 2 participants
0 0
Day 180; definite change; right eye; n=2, 2 Number Analyzed 2 participants 2 participants
0 0
Day 180; possible change; left eye; n=2, 2 Number Analyzed 2 participants 2 participants
0 0
Day 180; definite change; left eye; n=2, 2 Number Analyzed 2 participants 2 participants
0 1
22.Secondary Outcome
Title Number of Participants With Retinal Changes From Baseline
Hide Description 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).
Time Frame Baseline and up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Ophthalmic Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 27 13
Measure Type: Number
Unit of Measure: Participants
Day 29, Definite change, right eye; n=22, 13 Number Analyzed 22 participants 13 participants
0 0
Day 29, Ques change, right eye; n=22, 13 Number Analyzed 22 participants 13 participants
2 0
Day 29, Definite change, left eye; n=22, 13 Number Analyzed 22 participants 13 participants
0 0
Day 29, Ques change, left eye; n=22, 13 Number Analyzed 22 participants 13 participants
1 0
Day 90, Definite change, right eye; n=24, 11 Number Analyzed 24 participants 11 participants
0 0
Day 90, Ques change, right eye; n=24, 11 Number Analyzed 24 participants 11 participants
2 1
Day 90, Definite change, left eye; n=24, 11 Number Analyzed 24 participants 11 participants
0 0
Day 90, Ques change, left eye; n=24, 11 Number Analyzed 24 participants 11 participants
0 0
Day 180, Definite change, right eye; n=3, 2 Number Analyzed 3 participants 2 participants
0 0
Day 180, Ques change, right eye; n=3, 2 Number Analyzed 3 participants 2 participants
0 0
Day 180, Definite change, left eye; n=3, 2 Number Analyzed 3 participants 2 participants
0 0
Day 180, Ques change, left eye; n=3, 2 Number Analyzed 3 participants 2 participants
0 0
Maximum change post-Baseline; either eye; n=27, 13 Number Analyzed 27 participants 13 participants
0 0
23.Secondary Outcome
Title Change From Baseline in Percent Methemoglobin
Hide Description 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).
Time Frame Baseline and up to Day 120
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 166 85
Mean (Standard Deviation)
Unit of Measure: Percent change
Day 2, Male, n=114, 53 Number Analyzed 114 participants 53 participants
0.02  (0.754) 0.02  (0.406)
Day 2, Female, n=52, 32 Number Analyzed 52 participants 32 participants
-0.16  (1.168) -0.06  (0.181)
Day 3, Male, n=114, 53 Number Analyzed 114 participants 53 participants
0.18  (0.762) 0.03  (0.373)
Day 3, Female, n=52, 32 Number Analyzed 52 participants 32 participants
0.08  (1.264) 0.17  (0.663)
Day 5, Male, n=113, 53 Number Analyzed 113 participants 53 participants
0.77  (1.226) 0.89  (1.207)
Day 5, Female, n=52, 32 Number Analyzed 52 participants 32 participants
0.63  (1.354) 1.32  (1.400)
Day 8, Male, n=112, 52 Number Analyzed 112 participants 52 participants
1.22  (1.505) 2.63  (2.881)
Day 8, Female, n=52, 32 Number Analyzed 52 participants 32 participants
1.00  (1.755) 2.81  (2.530)
Day 11, Male, n=112, 52 Number Analyzed 112 participants 52 participants
1.16  (1.446) 3.30  (3.116)
Day 11, Female, n=51, 32 Number Analyzed 51 participants 32 participants
1.04  (1.656) 3.44  (2.651)
Day 15, Male, n=113, 52 Number Analyzed 113 participants 52 participants
1.01  (1.226) 3.26  (2.920)
Day 15, Female, n=52, 32 Number Analyzed 52 participants 32 participants
0.81  (1.474) 3.61  (2.324)
Day 22, Male, n=112, 52 Number Analyzed 112 participants 52 participants
0.61  (1.008) 1.58  (1.692)
Day 22, Female, n=52, 32 Number Analyzed 52 participants 32 participants
0.32  (1.364) 2.30  (1.900)
Day 29, Male, n=111, 52 Number Analyzed 111 participants 52 participants
0.24  (0.714) 0.46  (0.795)
Day 29, Female, n=52, 32 Number Analyzed 52 participants 32 participants
-0.02  (1.239) 0.84  (0.842)
Day 60, Male, n=107, 51 Number Analyzed 107 participants 51 participants
0.05  (0.583) 0.20  (1.220)
Day 60, Female, n=52, 32 Number Analyzed 52 participants 32 participants
-0.09  (1.202) 0.14  (0.496)
Day 120, Male, n=109, 50 Number Analyzed 109 participants 50 participants
0.06  (0.389) -0.01  (0.328)
Day 120, Female, n=50, 31 Number Analyzed 50 participants 31 participants
0.14  (1.676) 0.04  (0.422)
24.Secondary Outcome
Title Cost Associated With Relapse Episode of P Vivax Malaria
Hide Description 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).
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. Only those participants who experienced a relapse or who had a follow-up visit for a relapse were included in the analysis.
Arm/Group Title First Malaria Relapse First Malaria Relapse Follow-up
Hide Arm/Group Description:
Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.
Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Overall Number of Participants Analyzed 72 85
Mean (Standard Deviation)
Unit of Measure: US Dollars (USD)
Brazil; enrollment clinic for care; n=19, 17 Number Analyzed 19 participants 17 participants
8.208  (2.8369) 8.032  (2.2403)
Colombia; enrollment clinic for care; n=1,0 Number Analyzed 1 participants 0 participants
42.776  (0)
Colombia; attended another clinic; n=1,0 Number Analyzed 1 participants 0 participants
4.194  (0)
Colombia; hospital emergency center; n=1,1 Number Analyzed 1 participants 1 participants
16.775  (0) 16.775  (0)
Peru; enrollment clinic for care; n=32, 33 Number Analyzed 32 participants 33 participants
9.244  (2.8235) 8.815  (1.2803)
Peru; attended another clinic; n=8, 30 Number Analyzed 8 participants 30 participants
1.677  (0.9807) 3.959  (0.8522)
Peru; Other; n=8, 0 Number Analyzed 8 participants 0 participants
0.818  (0.4284)
Thailand; enrollment clinic for care; n=0, 1 Number Analyzed 0 participants 1 participants
1.534  (0)
Vietnam; drug shop for care;n=1, 2 Number Analyzed 1 participants 2 participants
0.702  (0) 2.809  (2.6483)
Vietnam; Other; n=1, 0 Number Analyzed 1 participants 0 participants
1.873  (0)
Vietnam; attended another clinic; n=0, 1 Number Analyzed 0 participants 1 participants
0.936  (0)
25.Secondary Outcome
Title Cost Associated With a Hemolysis Event
Hide Description 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.
Time Frame Up to Day 180
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Hide Analysis Population Description
Safety Population
Arm/Group Title Participants With Clinically Relevant Hemolysis
Hide Arm/Group Description:
Participants from both treatment arms (TQ + CQ and PQ + CQ) with clinically relevant hemolysis were included.
Overall Number of Participants Analyzed 1
Mean (Standard Deviation)
Unit of Measure: USD
9.174  (0)
26.Secondary Outcome
Title Cost Incurred With Purchase of Medications Associated With Relapse Episode of P. Vivax Malaria
Hide Description 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).
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title First Malaria Relapse First Malaria Relapse Follow-up
Hide Arm/Group Description:
Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.
Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Overall Number of Participants Analyzed 9 4
Mean (Standard Deviation)
Unit of Measure: USD
Colombia; n=2, 1 Number Analyzed 2 participants 1 participants
2.516  (2.3723) 4.194  (0)
Peru; n=6, 2 Number Analyzed 6 participants 2 participants
0.491  (0.1792) 0.327  (0.0000)
Vietnam; n=1, 1 Number Analyzed 1 participants 1 participants
0.468  (0) 2.341  (0)
27.Secondary Outcome
Title Cost Incurred With Purchase of Medications Associated With Hemolysis Event
Hide Description 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.
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Participants With Clinically Relevant Hemolysis
Hide Arm/Group Description:
Participants from both treatment arms (TQ + CQ and PQ + CQ) with clinically relevant hemolysis were included.
Overall Number of Participants Analyzed 1
Mean (Standard Deviation)
Unit of Measure: USD
0  (0)
28.Secondary Outcome
Title Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to Relapse Episode of Malaria
Hide Description 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).
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title First Malaria Relapse First Malaria Relapse Follow-up
Hide Arm/Group Description:
Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.
Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Overall Number of Participants Analyzed 61 61
Measure Type: Number
Unit of Measure: Participants
Brazil; Housework; n=2, 1 Number Analyzed 2 participants 1 participants
0 0
Brazil; Farming; n=1, 1 Number Analyzed 1 participants 1 participants
0 0
Brazil; Student; n=1, 1 Number Analyzed 1 participants 1 participants
0 0
Brazil; Paid employment; n=7, 7 Number Analyzed 7 participants 7 participants
0 0
Brazil; Other; n=8, 7 Number Analyzed 8 participants 7 participants
0 0
Colombia; Housework; n=1, 0 Number Analyzed 1 participants 0 participants
1
Colombia; Farming; n=2, 2 Number Analyzed 2 participants 2 participants
0 0
Colombia; Paid employment; n=1, 1 Number Analyzed 1 participants 1 participants
1 1
Peru; Housework; n=18, 18 Number Analyzed 18 participants 18 participants
14 15
Peru, Farming; n=4, 4 Number Analyzed 4 participants 4 participants
4 4
Peru; Student; n=3, 3 Number Analyzed 3 participants 3 participants
2 2
Peru; Paid employment; n=1, 1 Number Analyzed 1 participants 1 participants
1 1
Peru; Other; n=7, 7 Number Analyzed 7 participants 7 participants
7 6
Thailand; Farming; n=1, 1 Number Analyzed 1 participants 1 participants
1 1
Vietnam; Farming; n=4, 4 Number Analyzed 4 participants 4 participants
3 1
Vietnam; Paid employment; n=0, 3 Number Analyzed 0 participants 3 participants
2
29.Secondary Outcome
Title Number of Participants or Care Givers Who Had Taken Time Off From Normal Occupation Due to a Hemolysis Event
Hide Description 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.
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Participants With Clinically Relevant Hemolysis
Hide Arm/Group Description:
Participants from both treatment arms (TQ + CQ and PQ + CQ) with clinically relevant hemolysis were included.
Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: Participants
0
30.Secondary Outcome
Title Number of Participants With Action Taken to Treat Relapse Episode of P. Vivax Malaria
Hide Description 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).
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title First Malaria Relapse First Malaria Relapse Follow-up
Hide Arm/Group Description:
Participants from all treatment arms (CQ+TQ and PQ+TQ) with a relapse episode of malaria were included.
Participants from all treatment arms (CQ+TQ and PQ+TQ) who had a follow-up visit for relapse episode of malaria were included.
Overall Number of Participants Analyzed 61 61
Measure Type: Number
Unit of Measure: Participants
Brazil; Trial clinic; n=19, 17 Number Analyzed 19 participants 17 participants
19 17
Brazil; Other; n=19, 17 Number Analyzed 19 participants 17 participants
5 0
Colombia; Nothing; n=4, 3 Number Analyzed 4 participants 3 participants
2 2
Colombia; Trial clinic; n=4, 3 Number Analyzed 4 participants 3 participants
1 0
Colombia; Another clinic; n=4, 3 Number Analyzed 4 participants 3 participants
1 0
Colombia; Hospital emergency center; n=4, 3 Number Analyzed 4 participants 3 participants
1 1
Peru; Trial clinic; n=33, 33 Number Analyzed 33 participants 33 participants
32 33
Peru; Another clinic; n=33, 33 Number Analyzed 33 participants 33 participants
8 33
Peru; Other; n=33, 33 Number Analyzed 33 participants 33 participants
9 0
Thailand; Nothing; n=1, 1 Number Analyzed 1 participants 1 participants
1 0
Thailand; Trial Clinic; n=1, 1 Number Analyzed 1 participants 1 participants
0 1
Vietnam; Nothing; n=4, 7 Number Analyzed 4 participants 7 participants
1 5
Vietnam; Drug Shop; n=4, 7 Number Analyzed 4 participants 7 participants
2 2
Vietnam; Other; n=4, 7 Number Analyzed 4 participants 7 participants
1 0
Vietnam; Another clinic; n=4, 7 Number Analyzed 4 participants 7 participants
0 1
31.Secondary Outcome
Title Number of Participants With Action Taken to Treat a Hemolysis Event
Hide Description 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.
Time Frame Up to Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Participants With Clinically Relevant Hemolysis
Hide Arm/Group Description:
Participants from both treatment arms (TQ + CQ and PQ + CQ) with clinically relevant hemolysis were included.
Overall Number of Participants Analyzed 1
Measure Type: Number
Unit of Measure: Participants
1
32.Secondary Outcome
Title Oral Clearance (CL/F) of TQ
Hide Description Apparent population oral clearance of TQ
Time Frame Day 2, Day 3, Day 8, Day 15, Day 29, Day 60 and Day 180
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Hide Analysis Population Description
Safety Population
Arm/Group Title Participants in TQ Only Arms
Hide Arm/Group Description:
TQ only arms
Overall Number of Participants Analyzed 166
Median (90% Confidence Interval)
Unit of Measure: Liters per hour
2.96
(2.87 to 3.05)
33.Secondary Outcome
Title Volume of Distribution (Vc/F) of TQ
Hide Description Apparent population central volume of distribution of TQ
Time Frame Day 2, Day 3, Day 8, Day 15, Day 29, Day 60 and Day 180
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Participants in TQ Only Arms
Hide Arm/Group Description:
TQ only arms
Overall Number of Participants Analyzed 166
Median (90% Confidence Interval)
Unit of Measure: Liters
915
(879 to 956)
Time Frame 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)
Adverse Event Reporting Description Safety Population comprised of all randomized participants who received at least one dose of study medication.
 
Arm/Group Title TQ+CQ PQ+CQ
Hide Arm/Group Description 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. 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.
All-Cause Mortality
TQ+CQ PQ+CQ
Affected / at Risk (%) Affected / at Risk (%)
Total   0/166 (0.00%)      0/85 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
TQ+CQ PQ+CQ
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/166 (3.61%)      1/85 (1.18%)    
General disorders     
Pyrexia  1  1/166 (0.60%)  1 0/85 (0.00%)  0
Infections and infestations     
Pneumonia  1  1/166 (0.60%)  1 0/85 (0.00%)  0
Investigations     
Haemoglobin decreased  1  4/166 (2.41%)  4 1/85 (1.18%)  1
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TQ+CQ PQ+CQ
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   97/166 (58.43%)      50/85 (58.82%)    
Gastrointestinal disorders     
Nausea  1  21/166 (12.65%)  23 7/85 (8.24%)  12
Vomiting  1  15/166 (9.04%)  15 8/85 (9.41%)  8
Diarrhoea  1  12/166 (7.23%)  12 3/85 (3.53%)  3
Abdominal pain upper  1  10/166 (6.02%)  13 1/85 (1.18%)  1
General disorders     
Pyrexia  1  6/166 (3.61%)  7 6/85 (7.06%)  7
Asthenia  1  5/166 (3.01%)  5 5/85 (5.88%)  7
Infections and infestations     
Nasopharyngitis  1  14/166 (8.43%)  15 5/85 (5.88%)  5
Urinary tract infection  1  9/166 (5.42%)  11 9/85 (10.59%)  10
Pharyngitis  1  5/166 (3.01%)  5 6/85 (7.06%)  6
Musculoskeletal and connective tissue disorders     
Myalgia  1  15/166 (9.04%)  16 11/85 (12.94%)  13
Back pain  1  9/166 (5.42%)  11 3/85 (3.53%)  4
Nervous system disorders     
Dizziness  1  29/166 (17.47%)  35 16/85 (18.82%)  22
Headache  1  27/166 (16.27%)  34 16/85 (18.82%)  22
Skin and subcutaneous tissue disorders     
Pruritus  1  21/166 (12.65%)  23 19/85 (22.35%)  19
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02216123     History of Changes
Other Study ID Numbers: 116564
First Submitted: June 19, 2014
First Posted: August 13, 2014
Results First Submitted: November 1, 2017
Results First Posted: May 16, 2018
Last Update Posted: May 16, 2018