NCT01290601

Study to Evaluate the Efficacy and Safety of Tafenoquine for the Treatment of Plasmodium Vivax in Adults

A Randomized, Active-control, Double-blind, Double-dummy Study to Evaluate the Efficacy and Safety of Tafenoquine for the Treatment of Plasmodium Vivax in Adults

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 70 (actual)
• Sponsor: U.S. Army Medical Research and Development Command · Federal
• Sex: All
• Age: 20 Years – 60 Years
• Healthy volunteers: Not accepted

Summary

This Phase II study is designed to determine whether a single 600 mg dose or 400mg/day for 3 days of tafenoquine is efficacious, and well tolerated for clearing P. vivax malaria infection (blood schizontocidal and gametocytocidal activity) and preventing P. vivax relapse (hypnozoite eradication). It will also further establish the safety and tolerability of these doses of tafenoquine.

Detailed description

This was a randomized, active-control, double-blind, double-dummy study to be conducted in 2 sequential cohorts. Cohort 1 was randomized 2:1 to receive tafenoquine, 400mg/day for 3 days, or the standard blood schizontocidal dosing regimen of chloroquine (1000mg for 2 days followed by 500mg for 1 day) followed by a standard hypnozoite eradication dosing regimen for primaquine (15mg base per day for 14 days). Cohort 2 was to be randomized 2:1 to receive a single 600mg dose of tafenoquine or the standard blood schizontocidal dosing regimen of chloroquine (1000mg for 2 days followed by 500mg for 1 day) followed by a standard hypnozoite eradication dosing regimen for primaquine (15mg base per day for 14 days). A planned interim analysis was performed after all subjects in Cohort 1 had completed the day 28 assessment and an Independent Data Monitoring Committee (IDMC) convened to evaluate the efficacy and safety of the tafenoquine dosing regimen (400mg once per day for 3 days) used in Cohort 1. Only if the results from Cohort 1 met pre-defined efficacy and safety criteria was enrollment to begin for Cohort 2. The efficacy criterion for achieving the primary endpoint was that the lower limit of the one-sided 95% confidence interval was no less than 85%, and for safety that a review of trends in all AEs, tolerability, medical observations, methemoglobin and other lab data for all subjects indicated the dose was well tolerated. During the IDMC review it was determined that Cohort 1 failed to meet the pre-specified endpoint for the day 28 cure rate and therefore Cohort 2 should not be initiated and follow-up in Cohort 1 should be completed according to protocol. Following last subject last visit for Cohort 1 the study was terminated.

Conditions

• Malaria
• Plasmodium Vivax

Interventions

Type	Name	Description
DRUG	Tafenoquine	Tafenoquine: 2 capsules (200mg base/capsule for a total of 400mg base) and 4 chloroquine placebo capsules for 2 days, followed by 2 tafenoquine capsules and 2 chloroquine placebo capsules for 1 day, followed by 1 primaquine placebo capsule/day for 14 days.
DRUG	Chloroquine + Primaquine	Chloroquine (1000 mg chloroquine phosphate) and tafenoquine placebo x 2 day, followed by chloroquine (500 mg chloroquine phosphate) and tafenoquine placebo x 1day, followed by primaquine, 15 mg/day for 14 days.
DRUG	tafenoquine	Tafenoquine (600 mg base) and chloroquine placebo x 1d, chloroquine placebo x 2 days, followed by primaquine placebo for 14 days.
DRUG	Chloroquine + Primaquine	Chloroquine (1000 mg chloroquine phosphate) and tafenoquine placebo x 1 day, followed by chloroquine (1000 mg chloroquine phosphate) x 1 day, followed by chloroquine (500 mg chloroquine phosphate) x 1day, followed by primaquine, 15 mg/day for 14 days.

Timeline

• Start date: 2003-09-15
• Primary completion: 2005-01-10
• Completion: 2005-01-10
• First posted: 2011-02-07
• Last updated: 2018-02-23
• Results posted: 2018-01-25

Locations

1 site across 1 country: Thailand

Regulatory

• FDA-regulated drug study