An Evaluation of Weekly Tafenoquine

Phase 2

Completed

• Conditions: Falciparum Parasitaemia
• Interventions: Drug: Placebo; Drug: Tafenoquine; Drug: Mefloquine

• Registration Number: NCT02488980
• Lead Sponsor: U.S. Army Medical Research and Development Command

Brief Summary

This was a placebo controlled, randomised, double-blind, double-dummy study of the efficacy of weekly tafenoquine compared with weekly mefloquine or placebo in the chemosuppression of P. falciparum in Nyanza Province, western Kenya.

Detailed Description

Subjects were treated for 3 days with halofantrine to clear any existing parasitaemia. At the end of the clearance period, subjects free from malaria parasitaemia were randomized and received a loading dose of the study treatment (tafenoquine 200 mg, Mefloquine 250 mg or placebo) for tree days, followed by study treatment (tafenoquine 200 mg, mefloquine 250 mg or placebo, respectively) once a week for 24 weeks. After the treatment period subjects attended weekly follow-up safety visits until week 28.

Study Timeline

• Study Start: 2000-05
• Primary Completion: 2000-10
• Study Completion: 2003-03
• Study First Submitted: 2015-06-24
• Study First Submitted QC: 2015-07-01
• Study First Posted: 2015-07-02
• Results First Submitted: 2017-01-05
• Results First Submitted QC: 2017-01-05
• Results First Posted: 2017-02-24
• Status Verified: 2017-04
• Last Update Submitted: 2017-04-26
• Last Update Posted: 2017-05-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 306

Inclusion Criteria

• Healthy male or female volunteers who provided informed consent (a healthy volunteer was defined as one who was free of ailments that might cause difficulty in evaluating drug efficacy or adverse experiences).
• Subjects aged 18-55 years.
• Subjects planning to reside in the study area for the entire study duration of approximately 70 weeks

Exclusion Criteria

• Subjects with positive parasitaemia following halofantrine treatment for radical cure.
• Subjects with any medical condition which, in the opinion of the investigator, made the subject unsuitable to enter the study.
• Subjects with personal or family history of seizures.
• Female subjects with a positive serum beta-HCG5 (tested during screening and within 48 hours of first drug administration and approximately monthly thereafter).
• Women who were pregnant or lactating or who in the opinion of the investigator were at risk of becoming pregnant.
• Subjects with clinically significant abnormalities (to include but not limited to abnormal hepatic or renal function) as determined by history, physical and routine blood chemistries and haematology values. Subjects who had demonstrated hypersensitivity to any of the study drugs especially to any other 8-aminoquinolines.
• Subjects unwilling to report for drug administration or blood drawing during the 70 week duration of the study.
• Subjects with G6PD deficiency.
• Subjects with laboratory guideline values for exclusion: haemoglobin <10 gm/dL, platelets <80,000/mm3, WBC <3000ul3, creatinine or ALT more than twice the upper limit of normal for age.
• Subjects with an abnormal ECG, particularly an extended QTc interval > 0.42 seconds.
• Subjects taking any other anti-malarial product, or who had taken an antimalarial drug other than halofantrine within the previous two weeks.
• Subjects who had received an investigational drug (a new chemical entity not registered for use) within 30 days or 5 half-lives whichever was the longer.
• Subjects with a history of psychiatric disorder.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo
Tafenoquine	Tafenoquine	Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks.
Mefloquine	Mefloquine	Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Prophylactic Outcome Defined by the Subject Having no Positive Smears	24 Weeks	Prophylactic outcome (success/failure) at the end of the prophylactic treatment phase; outcome was based on absence/presence of asexual stage parasites of any Plasmodium species on a single blood smear.

Secondary Outcome Measures

Name	Time	Method
Protective Efficacy Based on Two Consecutive Positive Smears	24 Weeks	Kaplan-Meier survival curves were produced for time to parasitaemia for both first positive smear and two consecutive positive smears. Analysis was based on a calculation of protective efficacy (PE) of tefaenoquine, defined as (1-relative risk of developing parasitaemia tafenoquine: placebo) x100% and 95.5% confidence intervals were constructed for the relative risk using Koopman's method.
Time to a Single Positive Smear	24 Weeks	Kaplan-Meier survival curves were produced for time to parasitaemia for both first positive smear and two consecutive positive smears. 95.5% confidence intervals were constructed for the relative risk.