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Ph 2B/3 Tafenoquine (TFQ) Study in Prevention of Vivax Relapse

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ClinicalTrials.gov Identifier: NCT01376167
Recruitment Status : Completed
First Posted : June 20, 2011
Results First Posted : April 23, 2018
Last Update Posted : April 23, 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Malaria, Vivax
Interventions Drug: Chloroquine 600mg
Drug: Chloroquine 300mg
Drug: Tafenoquine 50mg
Drug: Tafenoquine 100mg
Drug: Tafenoquine 300mg
Drug: Tafenoquine 600mg
Drug: Primaquine 15mg
Drug: Chloroquine 600mg (Part 2 )
Drug: Chloroquine 300mg (Part 2 )
Drug: Tafenoquine 300mg (Part 2)
Drug: Primaquine 15mg (Part2 )
Enrollment 851

Recruitment Details This was a multi-centre, double-blind, randomized, parallel-group, active-controlled study to evaluate the efficacy, safety and tolerability of tafenoquine (TQ) in participants with Plasmodium vivax (P vivax) malaria. TAF112582 consisted of two parts-Part 1 (Phase 2 dose ranging) and Part 2 (Phase 3 pivotal). Results have been presented for Part 2.
Pre-assignment Details A total of 683 participants were screened of which 161 failed screening and 522 participants were randomized to receive chloroquine (CQ) + 300 milligrams (mg) TQ, CQ + 15 mg primaquine (PQ) and CQ alone regimen in a ratio of 2:1:1.
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2. Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2. Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Period Title: Overall Study
Started 133 260 129
Completed 129 250 123
Not Completed 4 10 6
Reason Not Completed
Lost to Follow-up             2             4             2
Physician Decision             1             1             0
Withdrawal by Subject             1             5             4
Arm/Group Title CQ Only TQ + CQ PQ + CQ Total
Hide Arm/Group Description Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2. Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2. Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2. Total of all reporting groups
Overall Number of Baseline Participants 133 260 129 522
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 133 participants 260 participants 129 participants 522 participants
35.3  (14.23) 35.0  (14.39) 34.7  (14.26) 35.0  (14.29)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 133 participants 260 participants 129 participants 522 participants
Female
36
  27.1%
64
  24.6%
30
  23.3%
130
  24.9%
Male
97
  72.9%
196
  75.4%
99
  76.7%
392
  75.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 133 participants 260 participants 129 participants 522 participants
American(Amer) Indian(Ind) or Alaska(Al) Native(N)
43
  32.3%
81
  31.2%
41
  31.8%
165
  31.6%
Asian-South East Asian (A) Heritage (Her)
26
  19.5%
50
  19.2%
26
  20.2%
102
  19.5%
Black or African (Afr) Amer
14
  10.5%
28
  10.8%
13
  10.1%
55
  10.5%
White-White/Caucasian(Cau)/European(Eur) Her
3
   2.3%
4
   1.5%
2
   1.6%
9
   1.7%
Multiple-Afr Amer/Afr Her/Amer Ind or Al N
47
  35.3%
95
  36.5%
47
  36.4%
189
  36.2%
Multiple-Afr Amer/Afr Her/White-White/Cau/Eur Her
0
   0.0%
1
   0.4%
0
   0.0%
1
   0.2%
Multiple-Amer Ind or Al N/A-Central/South A Her
0
   0.0%
1
   0.4%
0
   0.0%
1
   0.2%
1.Primary Outcome
Title Number of Participants With Recurrence-free Efficacy at 6 Months Post Dose
Hide Description A participant was considered to have demonstrated recurrence-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. Participants were censored if they did not have P.vivax at Baseline, or took a drug with anti-malarial action despite not having malaria parasites, or did not have a 6 month assessment. The number of participants with recurrence-free efficacy at 6 months has been summarized.
Time Frame 6 months post dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Microbiologic intent to treat (mITT) Population-all randomized participants who received at least one dose of study medication, who have at least one P vivax parasite assessment after randomization, and who have a positive parasite smear for P vivax at Baseline.
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Measure Type: Number
Unit of Measure: Participants
35 155 83
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CQ Only, TQ + CQ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The Cox proportional hazards model was fitted with region and treatment as covariates.
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.299
Confidence Interval (2-Sided) 95%
0.222 to 0.404
Estimation Comments A hazard ratio<1 indicated a lower chance of relapse compared to CQ only.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection CQ Only, PQ + CQ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The Cox proportional hazards model was fitted with region and treatment as covariates.
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.262
Confidence Interval (2-Sided) 95%
0.178 to 0.387
Estimation Comments A hazard ratio<1 indicated a lower chance of relapse compared to CQ only.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection CQ Only, TQ + CQ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Logistic regression model was fitted with region and treatment as covariates. Participants with a zero P vivax asexual parasite count at Baseline were excluded from the analysis.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.241
Confidence Interval (2-Sided) 95%
0.152 to 0.382
Estimation Comments Odds ratios < 1 suggested a smaller chance of recurrence compared to CQ Only.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection CQ Only, PQ + CQ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Logistic regression model was fitted with region and treatment as covariates. Participants with a zero P vivax asexual parasite count at Baseline were excluded from the analysis.
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.198
Confidence Interval (2-Sided) 95%
0.117 to 0.335
Estimation Comments Odds ratios < 1 suggested a smaller chance of recurrence compared to CQ Only.
2.Secondary Outcome
Title Number of Participants With Recurrence-free Efficacy at 4 Months Post Dose
Hide Description A participant (par) was considered to have demonstrated recurrence-free efficacy at 4 months if: a) Par had non-zero P vivax asexual parasite count at Baseline. b) Par showed initial clearance of P vivax parasitemia. c) Par had no positive asexual P vivax parasite count at any assessment prior to or on Study Day 130 following initial parasite clearance. d) Par 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) Par is parasite-free at 4 months defined as a negative asexual P vivax parasite count at the first parasite assessment performed after Study Day 109 (up to and including Study Day 130). Par were censored if they did not have P.vivax at Baseline, or took a drug with anti-malarial action despite not having malaria parasites or did not have a 4 month assessment. The number of par with recurrence-free efficacy at 4 months has been summarized.
Time Frame 4 months post dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Measure Type: Number
Unit of Measure: Participants
47 177 90
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CQ Only, TQ + CQ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The Cox proportional hazards model was fitted with region and treatment as covariates.
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.271
Confidence Interval (2-Sided) 95%
0.195 to 0.376
Estimation Comments A hazard ratio<1 indicated a lower chance of relapse compared to CQ only.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection CQ Only, PQ + CQ
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The Cox proportional hazards model was fitted with region and treatment as covariates.
Method Cox Proportional Hazards Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.255
Confidence Interval (2-Sided) 95%
0.167 to 0.390
Estimation Comments A hazard ratio<1 indicated a lower chance of relapse compared to CQ only.
3.Secondary Outcome
Title Time to Recurrence of P Vivax Malaria
Hide Description Recurrence was defined as the first confirmed presence of P vivax asexual stage parasites after clearance of initial parasitemia following CQ treatment. Time to recurrence was defined as the time (in days) from initial parasite clearance to recurrence. The time to recurrence was analyzed by the Kaplan-Meier method. NA indicates data was not available due to insufficient number of participants with events during the follow up period in the study. The median number of days to recurrence along with 95% confidence interval has been presented for each treatment group.
Time Frame Up to Day 180
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Median (95% Confidence Interval)
Unit of Measure: Days
86
(63 to 109)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
Insufficient number of participants with events during the follow up period in the study.
4.Secondary Outcome
Title Time to Parasite Clearance
Hide Description Parasite clearance time was 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. The time taken to achieve parasite clearance was analyzed using 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Median (95% Confidence Interval)
Unit of Measure: Hours
43
(41 to 48)
45
(42 to 47)
42
(39 to 45)
5.Secondary Outcome
Title Time to Fever Clearance
Hide Description Fever clearance time was defined as 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 37.40 degree Celsius is reduced to a value less than or equal to 37.40 degree Celsius and in the absence of value more than 37.40 degree Celsius in the following 48 hours up to the Day 8 visit. The time taken to achieve fever clearance was analyzed using Kaplan Meier Methodology. The median fever clearance time along with 95% confidence interval has been presented for each treatment group.
Time Frame Up to Day 180
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Median (95% Confidence Interval)
Unit of Measure: Hours
7
(5 to 14)
7
(5 to 12)
8
(6 to 18)
6.Secondary Outcome
Title Number of Participants With Hemoglobin Decline From Baseline Over First 29 Days
Hide Description Glucose-6-phosphate dehydrogenase deficiency (G6PD) deficiency is known to be a risk factor for hemolysis in participants treated with 8-aminoquinolines. Blood samples were collected for the evaluation of hemoglobin levels. Hemoglobin decreases of >=30% or >3 grams/deciliter (g/dL) from Baseline; or, an overall drop in hemoglobin below 6.0 g/dL in the first 15 days of the study were considered as protocol defined serious adverse events (SAEs). Number of participants with maximum hemoglobin decline from Baseline over first 29 days of study has been summarized. Safety Population consisted of all randomized participants who received at least one dose of study medication.
Time Frame Baseline and up to Day 29
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 259 129
Measure Type: Number
Unit of Measure: Participants
<=20 grams/liter (g/L) 120 214 114
>20g/L to <=30 g/L 11 31 12
>30 g/L or >=30% 2 14 3
7.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) Potentially Related to Hemoglobin Decrease
Hide Description TEAEs are defined as adverse events (AEs) with an onset date and time on or after that of the start of first dose of study medication (including CQ). The number of participants with TEAEs potentially related to hemoglobin decrease has been presented.
Time Frame Up to Day 180
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Measure Type: Number
Unit of Measure: Participants
Haemoglobin decreased 2 14 2
Fatigue 2 1 0
Hyperbilirubinaemia 1 0 0
Pallor 0 1 0
8.Secondary Outcome
Title Number of Participants Who Received Blood Transfusion
Hide Description The number of participants who received blood transfusion as a result of hemoglobin decline has been summarized.
Time Frame Up to Day 180
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Measure Type: Number
Unit of Measure: Participants
0 0 0
9.Secondary Outcome
Title Number of Participants With Acute Renal Failure
Hide Description There were no participants with acute renal failure in the study.
Time Frame Up to Day 180
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Measure Type: Number
Unit of Measure: Participants
0 0 0
10.Secondary Outcome
Title Change From Baseline in Percent Methemoglobin
Hide Description Methemoglobin assessment was made with the aid of a non-invasive signal extraction pulse CO-Oximeter handheld machine (Masimo). The change from Baseline in percent methemoglobin by treatment, time and sex has been summarized. The last assessment performed prior to the first dose of study medication (CQ or randomized treatment) was considered as Baseline. Change from Baseline was calculated as the post baseline assessment minus the Baseline assessment for percent methemoglobin. Only those participants with data available at the specified data points were analyzed.
Time Frame Baseline and up to Day 120
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Mean (Standard Deviation)
Unit of Measure: Percent Methemoglobin
Day 2, Male Number Analyzed 95 participants 195 participants 98 participants
-0.18  (1.525) -0.03  (1.246) -0.10  (1.372)
Day 2, Female Number Analyzed 36 participants 64 participants 30 participants
-0.22  (0.895) 0.10  (0.830) -0.01  (0.438)
Day 3, Male Number Analyzed 97 participants 195 participants 99 participants
-0.15  (1.256) -0.01  (1.254) -0.02  (1.454)
Day 3, Female Number Analyzed 36 participants 64 participants 30 participants
-0.20  (0.902) 0.26  (0.781) 0.11  (0.443)
Day 5, Male Number Analyzed 94 participants 192 participants 94 participants
-0.28  (1.329) 0.42  (1.633) 1.28  (2.619)
Day 5, Female Number Analyzed 35 participants 63 participants 30 participants
-0.20  (0.789) 1.37  (1.263) 0.90  (0.885)
Day 8, Male Number Analyzed 97 participants 191 participants 96 participants
-0.12  (1.135) 0.98  (1.870) 3.01  (3.214)
Day 8, Female Number Analyzed 35 participants 64 participants 30 participants
-0.16  (0.857) 2.04  (1.716) 2.58  (2.565)
Day 11, Male Number Analyzed 97 participants 190 participants 95 participants
-0.07  (1.348) 1.17  (2.074) 3.61  (3.498)
Day 11, Female Number Analyzed 34 participants 64 participants 30 participants
-0.13  (0.676) 2.13  (1.667) 3.41  (2.659)
Day 15, Male Number Analyzed 96 participants 189 participants 94 participants
0.12  (1.404) 0.94  (1.963) 3.51  (3.369)
Day 15, Female Number Analyzed 35 participants 64 participants 30 participants
-0.08  (0.684) 1.67  (1.349) 3.63  (2.678)
Day 22, Male Number Analyzed 95 participants 187 participants 94 participants
0.07  (1.211) 0.54  (1.431) 1.96  (2.401)
Day 22, Female Number Analyzed 35 participants 64 participants 30 participants
-0.05  (0.467) 0.93  (1.042) 1.86  (1.494)
Day 29, Male Number Analyzed 95 participants 190 participants 93 participants
-0.10  (1.428) 0.23  (1.350) 0.58  (1.835)
Day 29, Female Number Analyzed 35 participants 64 participants 30 participants
-0.18  (0.927) 0.24  (0.717) 0.49  (0.502)
Day 60, Male Number Analyzed 94 participants 190 participants 95 participants
0.44  (1.925) -0.10  (1.362) 0.20  (1.940)
Day 60, Female Number Analyzed 35 participants 64 participants 30 participants
0.19  (1.080) 0.03  (0.700) 0.16  (0.620)
Day 120, Male Number Analyzed 93 participants 187 participants 93 participants
0.20  (1.783) 0.07  (1.503) 0.37  (2.153)
Day 120, Female Number Analyzed 35 participants 63 participants 30 participants
0.10  (1.332) -0.03  (0.906) 0.37  (1.552)
11.Secondary Outcome
Title Number of Participants With Gastrointestinal Disorders
Hide Description Gastrointestinal tolerability was analyzed by the number of par experiencing gastrointestinal disorders such as abdominal pain, heartburn, diarrhea, constipation, nausea, and vomiting. The number of participants with gastrointestinal disorders for each treatment group has been summarized.
Time Frame Up to Day 180
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Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Measure Type: Number
Unit of Measure: Participants
Nausea 12 21 9
Vomiting 9 22 11
Abdominal pain upper 13 11 7
Diarrhoea 6 15 5
Abdominal pain 5 8 6
Dyspepsia 5 6 2
12.Secondary Outcome
Title Number of Participants With Keratopathy
Hide Description Ophthalmic assessments were carried out at pre-qualified sites (Manaus) 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. The number of participants displaying keratopathy in each eye was summarized for each visit. The number of participants with new keratopathy at any time post Baseline was 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.
Time Frame Up to Day 180
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Ophthalmic Safety Population. Day 180 was not a required follow up assessment, hence, data was not collected for most participants.
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 29 65 31
Measure Type: Number
Unit of Measure: Participants
Baseline; right eye Number Analyzed 29 participants 65 participants 31 participants
0 0 0
Baseline; left eye Number Analyzed 29 participants 65 participants 31 participants
0 0 0
Day 1; right eye Number Analyzed 29 participants 65 participants 31 participants
0 0 0
Day 1; left eye Number Analyzed 29 participants 65 participants 31 participants
0 0 0
Day 29; right eye Number Analyzed 27 participants 60 participants 29 participants
0 0 0
Day 29; left eye Number Analyzed 27 participants 60 participants 29 participants
0 0 0
Day 90; right eye Number Analyzed 28 participants 62 participants 31 participants
0 1 0
Day 90; left eye Number Analyzed 28 participants 62 participants 31 participants
0 0 0
Day 180; right eye Number Analyzed 0 participants 3 participants 1 participants
0 0
Day 180; left eye Number Analyzed 0 participants 3 participants 1 participants
0 0
Any time post Baseline; right eye Number Analyzed 29 participants 65 participants 31 participants
0 1 0
Any time post Baseline; left eye Number Analyzed 29 participants 65 participants 31 participants
0 0 0
13.Secondary Outcome
Title Incidence of Visual Field Abnormalities Based on Best Corrected Visual Acuity Test Scores
Hide Description Ophthalmic assessments were carried out at pre-qualified sites (Manaus) 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. 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 mean and standard deviation of logMAR score for each treatment group has been summarized. High scores were associated with worse vision, and low scores with better vision. Only those participants with data available at the specified data points were analyzed.
Time Frame Up to Day 180
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Hide Analysis Population Description
Ophthalmic Safety Population. Day 180 was not a required follow up assessment, hence, data was not collected for most participants.
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 29 65 31
Mean (Standard Deviation)
Unit of Measure: logMAR scores
Baseline; right eye Number Analyzed 29 participants 65 participants 31 participants
0.041  (0.0825) 0.046  (0.1045) 0.029  (0.0461)
Baseline; left eye Number Analyzed 29 participants 65 participants 31 participants
0.048  (0.0859) 0.039  (0.0652) 0.048  (0.1306)
Day 29; right eye Number Analyzed 27 participants 60 participants 29 participants
0.039  (0.0906) 0.049  (0.1159) 0.021  (0.0412)
Day 29; left eye Number Analyzed 27 participants 60 participants 29 participants
0.032  (0.0580) 0.032  (0.0565) 0.045  (0.1325)
Day 90; right eye Number Analyzed 28 participants 62 participants 31 participants
0.044  (0.0928) 0.038  (0.1083) 0.016  (0.0374)
Day 90; left eye Number Analyzed 28 participants 62 participants 31 participants
0.041  (0.0599) 0.028  (0.0971) 0.041  (0.1303)
Day 180; right eye Number Analyzed 0 participants 3 participants 1 participants
0.033  (0.0577) 0.000 [1]   (NA)
Day 180; left eye Number Analyzed 0 participants 3 participants 1 participants
0.033  (0.0577) 0.000 [1]   (NA)
[1]
Standard Deviation not calculable because data were only collected for 1 participant
14.Secondary Outcome
Title Number of Participants With Retinal Changes From Baseline
Hide Description Ophthalmic assessments were carried out at pre-qualified sites (Manaus) 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 was calculated as the post Baseline assessment minus the Baseline assessment. The number of participants with definite retinal change and questionable (ques) retinal change from Baseline was presented. Only those participants with data available at the specified data points were analyzed.
Time Frame Baseline and up to Day 180
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Ophthalmic Safety Population. Day 180 was not a required follow up assessment, hence, data was not collected for most participants.
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 29 65 31
Measure Type: Number
Unit of Measure: Participants
Day 29, Definite change, right eye Number Analyzed 24 participants 53 participants 23 participants
1 0 0
Day 29, Ques change, right eye Number Analyzed 24 participants 53 participants 23 participants
0 0 0
Day 29, Definite change, left eye Number Analyzed 24 participants 53 participants 23 participants
1 0 0
Day 29, Ques change, left eye Number Analyzed 24 participants 53 participants 23 participants
0 0 0
Day 90, Definite change, right eye Number Analyzed 24 participants 48 participants 23 participants
1 1 1
Day 90, Ques change, right eye Number Analyzed 24 participants 48 participants 23 participants
0 0 1
Day 90, Definite change, left eye Number Analyzed 24 participants 48 participants 23 participants
1 1 0
Day 90, Ques change, left eye Number Analyzed 24 participants 48 participants 23 participants
0 1 2
Day 180, Definite change, right eye Number Analyzed 1 participants 7 participants 0 participants
0 0
Day 180, Ques change, right eye Number Analyzed 1 participants 7 participants 0 participants
0 0
Day 180, Definite change, left eye Number Analyzed 1 participants 7 participants 0 participants
0 0
Day 180, Ques change, left eye Number Analyzed 1 participants 7 participants 0 participants
0 0
15.Secondary Outcome
Title Number of Participants With TEAEs and Serious TEAEs
Hide Description An AE is defined as any untoward medical occurrence in a participant under clinical investigation, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. 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 and is associated with possible drug induced liver injury with hyperbilirubinemia. TEAEs is 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
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Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Measure Type: Number
Unit of Measure: Participants
TEAEs 86 164 76
Serious TEAEs 6 21 4
16.Secondary Outcome
Title Number of Participants With TEAEs by Maximum Intensity
Hide Description An AE is defined as any untoward medical occurrence in a participant under clinical investigation, temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAE is 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 AEs based on severity has been presented.
Time Frame Up to Day 180
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Hide Analysis Population Description
Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 65 31
Measure Type: Number
Unit of Measure: Participants
Mild or Grade 1 30 70 38
Moderate or Grade 2 52 89 37
Severe or Grade 3 3 2 1
Grade 4 1 0 0
Grade 5 0 1 0
17.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) was 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. Only those participants with data available at the specified data points were analyzed.
Time Frame Up to Day 120
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Hide Analysis Population Description
Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 260 129
Measure Type: Number
Unit of Measure: Participants
Blood eosinophils, High Number Analyzed 133 participants 259 participants 129 participants
18 38 28
Blood leukocytes, Low Number Analyzed 133 participants 259 participants 129 participants
0 3 2
Blood lymphocytes, Low Number Analyzed 133 participants 259 participants 129 participants
7 4 0
Blood lymphocytes, High Number Analyzed 133 participants 259 participants 129 participants
23 32 13
Blood neutrophils, Low Number Analyzed 133 participants 259 participants 129 participants
2 5 7
Blood platelets, Low Number Analyzed 133 participants 259 participants 129 participants
14 35 15
Blood reticulocytes, High Number Analyzed 133 participants 259 participants 129 participants
72 141 85
Methemoglobin, High Number Analyzed 133 participants 260 participants 129 participants
4 5 11
18.Secondary Outcome
Title Number of Participants With Clinical Chemistry Laboratory Data Outside the Reference Range
Hide Description Blood samples were collected for the evaluation of clinical chemistry parameters including Alanine Aminotransferase (ALT), Alkaline Phosphatase (Alk. Phos), Aspartate Aminotransferase (AST), bilirubin, creatine kinase, creatinine, glomerular filtration rate (GFR), indirect bilirubin and urea. The number of participants with clinical chemistry laboratory data outside the extended normal range (F3) was 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. Only those participants with data available at the specified data points were analyzed.
Time Frame Up to Day 120
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description:
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2.
Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
Overall Number of Participants Analyzed 133 259 129
Measure Type: Number
Unit of Measure: Participants
ALT, High 11 10 5
Alk Phos, High 3 1 1
AST, High 5 7 2
Bilirubin, High 18 23 12
Creatine kinase, High 8 5 8
Creatinine, High 0 1 0
GFR, Low 0 1 0
Indirect bilirubin 11 22 8
Urea, High 42 85 46
19.Secondary Outcome
Title Cost Associated With Recurrence 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 (inpatient/outpatient), traditional healer, other). The reported costs by type and by site has been summarized. Where costs have not been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed.
Time Frame Up to Day 180
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Safety Population
Arm/Group Title First Malaria Recurrence First Malaria Recurrence Follow-up
Hide Arm/Group Description:
Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) with a recurrence episode of malaria were included.
Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) who had a follow-up visit for recurrence episode of malaria were included.
Overall Number of Participants Analyzed 193 193
Mean (Standard Deviation)
Unit of Measure: US Dollars (USD)
Brazil (Drug shop for care) Number Analyzed 2 participants 0 participants
4.76  (3.24)
Brazil (Enrollment clinic for care) Number Analyzed 59 participants 72 participants
6.17  (2.39) 6.15  (2.14)
Brazil (other location for care) Number Analyzed 1 participants 0 participants
4.23  (0)
Peru (Drug shop for care) Number Analyzed 8 participants 0 participants
1.47  (1.30)
Peru (Enrollment clinic for care) Number Analyzed 61 participants 63 participants
8.78  (7.94) 8.54  (8.52)
Peru (Attended another clinic) Number Analyzed 7 participants 44 participants
2.71  (4.69) 3.94  (1.42)
Peru (Other location for care) Number Analyzed 15 participants 1 participants
0.72  (0.41) 1.30  (0)
Thailand (Drug shop for care) Number Analyzed 1 participants 0 participants
4.60  (0)
Thailand (Enrollment clinic for care) Number Analyzed 13 participants 0 participants
19.15  (10.60)
Thailand (In-hospital care) Number Analyzed 1 participants 0 participants
6.13  (0)
20.Secondary Outcome
Title Cost Incurred With Purchase of Medications Associated With Recurrence Episode of Malaria
Hide Description Health outcomes were evaluated based on the cost of medications purchased. The reported total medication cost for paracetamol associated with recurrence episode of P vivax malaria has been reported by site. Where costs have not been reported at a visit, the number of participants analyzed is given as 0. 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.
Time Frame Up to Day 180
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Hide Analysis Population Description
Safety Population
Arm/Group Title First Malaria Recurrence First Malaria Recurrence Follow-up
Hide Arm/Group Description:
Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) with a recurrence episode of malaria were included.
Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) who had a follow-up visit for recurrence episode of malaria were included.
Overall Number of Participants Analyzed 29 3
Mean (Standard Deviation)
Unit of Measure: USD
Peru, n=23, 3 Number Analyzed 23 participants 3 participants
0.49  (0.1941) 0.32  (1)
Brazil, n=6, 0 Number Analyzed 6 participants 0 participants
1.70  (0.144)
21.Secondary Outcome
Title Time Lost by Participants or Care Givers From Normal Occupation
Hide Description Health outcomes were evaluated based on total time lost by participants or care givers due to an episode of malaria. The reported time lost due to recurrence episode of P vivax malaria has been summarized by category and by site. Where categories by site have not been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed.
Time Frame Up to Day 180
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Hide Analysis Population Description
Safety Population
Arm/Group Title First Malaria Recurrence First Malaria Recurrence Follow-up
Hide Arm/Group Description:
Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) with a recurrence episode of malaria were included.
Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) who had a follow-up visit for recurrence episode of malaria were included.
Overall Number of Participants Analyzed 193 188
Measure Type: Number
Unit of Measure: Days
Brazil, Housework Number Analyzed 16 participants 15 participants
1 0
Brazil, Farming Number Analyzed 5 participants 4 participants
8 0
Brazil, paid employment Number Analyzed 44 participants 43 participants
8 0
Brazil, Other Number Analyzed 17 participants 16 participants
3 5
Cambodia, Farming Number Analyzed 12 participants 12 participants
17 24
Ethiopia, Housework Number Analyzed 3 participants 3 participants
4 3
Ethiopia, Farming Number Analyzed 2 participants 2 participants
2.5 3
Ethiopia, Student Number Analyzed 2 participants 2 participants
3 0
Ethiopia, Paid employment Number Analyzed 4 participants 4 participants
2 4
Ethiopia, Other Number Analyzed 3 participants 3 participants
1 7
Peru, Housework Number Analyzed 21 participants 21 participants
24 29
Peru, Farming Number Analyzed 14 participants 14 participants
19 28
Peru, Student Number Analyzed 2 participants 2 participants
1 6
Peru, Paid employment Number Analyzed 6 participants 6 participants
6 8.5
Peru, Other Number Analyzed 20 participants 20 participants
26 32
Philippines, Farming Number Analyzed 1 participants 0 participants
0
Thailand, paid employment Number Analyzed 14 participants 14 participants
20 0
Thailand, Other Number Analyzed 2 participants 2 participants
1 0
22.Secondary Outcome
Title Number of Participants With Action Taken to Treat Recurrence Episode of P Vivax Malaria
Hide Description Health outcomes were evaluated based on the actions taken by the participants to treat recurrence episode of P vivax malaria. The reported action taken by site is summarized. Where no action by site have been reported at a visit, the number of participants analyzed is given as 0. Only those participants with data available at the specified data points were analyzed.
Time Frame Up to Day 180
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title First Malaria Recurrence First Malaria Recurrence Follow-up
Hide Arm/Group Description:
Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) with a recurrence episode of malaria were included.
Participants from all treatment arms (CQ only, CQ+TQ and PQ+TQ) who had a follow-up visit for recurrence episode of malaria were included.
Overall Number of Participants Analyzed 193 188
Measure Type: Number
Unit of Measure: Participants
Brazil, Nothing Number Analyzed 86 participants 81 participants
21 5
Brazil, Drug shop Number Analyzed 86 participants 81 participants
2 0
Brazil, Trial clinic Number Analyzed 86 participants 81 participants
62 76
Brazil, Other Number Analyzed 86 participants 81 participants
2 0
Cambodia, Nothing Number Analyzed 13 participants 14 participants
13 14
Ethiopia, Nothing Number Analyzed 14 participants 14 participants
12 13
Ethiopia, Another clinic Number Analyzed 14 participants 14 participants
1 0
Ethiopia, Other Number Analyzed 14 participants 14 participants
1 0
Ethiopia, Trial clinic Number Analyzed 14 participants 14 participants
0 1
Peru, Nothing Number Analyzed 63 participants 63 participants
1 0
Peru, Drug shop Number Analyzed 63 participants 63 participants
8 0
Peru, Trial clinic Number Analyzed 63 participants 63 participants
61 63
Peru, Another clinic Number Analyzed 63 participants 63 participants
10 54
Peru, Other Number Analyzed 63 participants 63 participants
15 1
Philippines, Nothing Number Analyzed 1 participants 0 participants
1
Thailand, Nothing Number Analyzed 16 participants 16 participants
1 16
Thailand, Drug shop Number Analyzed 16 participants 16 participants
1 0
Thailand, Trial clinic Number Analyzed 16 participants 16 participants
13 0
Thailand, In hospital Number Analyzed 16 participants 16 participants
1 0
23.Secondary Outcome
Title Oral Clearance (CL/F) of TQ
Hide Description Apparent population oral clearance of TQ
Time Frame Day 2, Day 8, Day 15, Day 29 and Day 60
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Safety Population
Arm/Group Title Participants in TQ Only Arms
Hide Arm/Group Description:
TQ only arms
Overall Number of Participants Analyzed 259
Median (90% Confidence Interval)
Unit of Measure: Liters per hour
2.96
(2.87 to 3.05)
24.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 8, Day 15, Day 29 and Day 60
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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 259
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 CQ Only TQ + CQ PQ + CQ
Hide Arm/Group Description Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. TQ placebo was administered on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2. Participants were administered a single oral dose of CQ 600 mg on Days 1 and Day 2 and CQ 300 mg on Day 3. Participants were dosed with TQ 300 mg either on Day 1 or Day 2. PQ placebo capsule was administered once daily for 14 days starting from either Day 1 or Day 2. Participants were administered a single oral dose of CQ 600 mg on Days 1 and 2 and CQ 300 mg on Day 3. Participants were dosed with TQ placebo either on Day 1 or Day 2 and PQ 15 mg was administered once daily for 14 days starting from either Day 1 or Day 2.
All-Cause Mortality
CQ Only TQ + CQ PQ + CQ
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/133 (0.00%)      0/260 (0.00%)      0/129 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
CQ Only TQ + CQ PQ + CQ
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/133 (4.51%)      21/260 (8.08%)      4/129 (3.10%)    
Gastrointestinal disorders       
Diarrhoea  1  0/133 (0.00%)  0 1/260 (0.38%)  1 1/129 (0.78%)  1
Nausea  1  0/133 (0.00%)  0 0/260 (0.00%)  0 1/129 (0.78%)  1
Vomiting  1  0/133 (0.00%)  0 0/260 (0.00%)  0 1/129 (0.78%)  1
Hepatobiliary disorders       
Drug-induced liver injury  1  0/133 (0.00%)  0 1/260 (0.38%)  1 0/129 (0.00%)  0
Infections and infestations       
Abscess limb  1  0/133 (0.00%)  0 1/260 (0.38%)  1 0/129 (0.00%)  0
Gastroenteritis  1  1/133 (0.75%)  1 0/260 (0.00%)  0 0/129 (0.00%)  0
Hepatitis E  1  0/133 (0.00%)  0 1/260 (0.38%)  1 0/129 (0.00%)  0
Urinary tract infection  1  0/133 (0.00%)  0 1/260 (0.38%)  1 0/129 (0.00%)  0
Investigations       
Haemoglobin decreased  1  2/133 (1.50%)  2 14/260 (5.38%)  14 2/129 (1.55%)  2
Electrocardiogram QT prolonged  1  3/133 (2.26%)  3 0/260 (0.00%)  0 0/129 (0.00%)  0
Metabolism and nutrition disorders       
Dehydration  1  0/133 (0.00%)  0 0/260 (0.00%)  0 1/129 (0.78%)  1
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  0/133 (0.00%)  0 1/260 (0.38%)  1 0/129 (0.00%)  0
Reproductive system and breast disorders       
Menorrhagia  1  0/133 (0.00%)  0 1/260 (0.38%)  1 0/129 (0.00%)  0
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%
CQ Only TQ + CQ PQ + CQ
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   72/133 (54.14%)      119/260 (45.77%)      56/129 (43.41%)    
Gastrointestinal disorders       
Nausea  1  12/133 (9.02%)  13 21/260 (8.08%)  22 8/129 (6.20%)  8
Vomiting  1  9/133 (6.77%)  10 22/260 (8.46%)  22 10/129 (7.75%)  10
Abdominal pain upper  1  13/133 (9.77%)  13 11/260 (4.23%)  14 7/129 (5.43%)  9
Diarrhoea  1  6/133 (4.51%)  6 14/260 (5.38%)  14 4/129 (3.10%)  4
Infections and infestations       
Nasopharyngitis  1  7/133 (5.26%)  7 19/260 (7.31%)  19 9/129 (6.98%)  11
Pharyngitis  1  4/133 (3.01%)  4 13/260 (5.00%)  14 8/129 (6.20%)  8
Investigations       
Blood creatine phosphokinase increased  1  8/133 (6.02%)  9 10/260 (3.85%)  10 7/129 (5.43%)  7
Alanine aminotransferase increased  1  8/133 (6.02%)  8 6/260 (2.31%)  6 3/129 (2.33%)  3
Musculoskeletal and connective tissue disorders       
Myalgia  1  19/133 (14.29%)  24 15/260 (5.77%)  15 10/129 (7.75%)  11
Nervous system disorders       
Headache  1  19/133 (14.29%)  23 27/260 (10.38%)  34 10/129 (7.75%)  13
Dizziness  1  11/133 (8.27%)  13 25/260 (9.62%)  30 9/129 (6.98%)  9
Skin and subcutaneous tissue disorders       
Pruritus  1  20/133 (15.04%)  23 34/260 (13.08%)  35 14/129 (10.85%)  14
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: NCT01376167     History of Changes
Other Study ID Numbers: 112582
TAF112582
First Submitted: June 16, 2011
First Posted: June 20, 2011
Results First Submitted: October 27, 2017
Results First Posted: April 23, 2018
Last Update Posted: April 23, 2018