An Evaluation of Weekly Tafenoquine

A Randomized, Double Blind, Placebo Controlled Evaluation of Weekly Tafenoquine (WR 238605/SB252263) Compared to Mefloquine for Chemosuppression of Plasmodium Falciparum in Western Kenya

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.

Study Overview

• Status: Completed
• Conditions: Falciparum Parasitaemia
• Intervention / Treatment: Drug: Tafenoquine; Drug: Mefloquine; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 306
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo for three days followed by placebo once a week for 24 weeks
Experimental: Tafenoquine; Tafenoquine 200 mg for three days followed by Tafenoquine 200 once a week for 24 weeks.	Drug: Tafenoquine; Tafenoquine 200 mg for three days followed by Tafenoquine 200 mg once a week for 24 weeks.
Active Comparator: Mefloquine; Mefloquine 250 mg for three days followed by Mefloquine 250 once a week for 24 weeks.	Drug: Mefloquine; Mefloquine 250 mg for three days followed by Mefloquine 250 mg once a week for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prophylactic Outcome Defined by the Subject Having no Positive Smears	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.	24 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protective Efficacy Based on Two Consecutive Positive Smears	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.	24 Weeks
Time to a Single Positive Smear	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.	24 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety (SAEs and AEs)	The most commonly reported experiences in subject occurring in at least 20% of subjects in any treatment group.	28 weeks

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: SmithKline Beecham
• Investigators: Principal Investigator: Jose Stoute, MD, Penn State Hershey Infectious Diseases

Publications and helpful links

General Publications

• Novitt-Moreno A, Ransom J, Dow G, Smith B, Read LT, Toovey S. Tafenoquine for malaria prophylaxis in adults: An integrated safety analysis. Travel Med Infect Dis. 2017 May-Jun;17:19-27. doi: 10.1016/j.tmaid.2017.05.008. Epub 2017 May 8.

Study record dates

Study Major Dates

• Study Start: May 1, 2000
• Primary Completion (Actual): October 1, 2000
• Study Completion (Actual): March 1, 2003

Study Registration Dates

• First Submitted: June 24, 2015
• First Submitted That Met QC Criteria: July 1, 2015
• First Posted (Estimate): July 2, 2015

Study Record Updates

• Last Update Posted (Actual): May 30, 2017
• Last Update Submitted That Met QC Criteria: April 26, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Falciparum Parasitaemia, Malaria
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Parasitic Diseases; Parasitemia; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Mefloquine; Tafenoquine
• Other Study ID Numbers: A-9467

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: SmithKline Beecham