Clinical trial NCT02488980: An Evaluation of Weekly Tafenoquine
Official title: A Randomized, Double Blind, Placebo Controlled Evaluation of Weekly Tafenoquine (WR 238605/SB252263) Compared to Mefloquine for Chemosuppression of Plasmodium Falciparum in Western Kenya
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Falciparum Parasitaemia
Keywords: Falciparum Parasitaemia, Malaria
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: SmithKline Beecham
First posted: 2015-07-02
Enrollment: 306
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Prophylactic Outcome Defined by the Subject Having no Positive Smears
timeFrame: 24 Weeks
Secondary outcomes:
measure: Protective Efficacy Based on Two Consecutive Positive Smears
timeFrame: 24 Weeks
measure: Time to a Single Positive Smear
timeFrame: 24 Weeks
Other outcomes:
measure: Safety (SAEs and AEs)
timeFrame: 28 weeks
Locations:
Study officials:
affiliation: Penn State Hershey Infectious Diseases
name: Jose Stoute, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.