A Randomized, Double-blind, Placebo-controlled Evaluation of Increasing Doses of Weekly Tafenoquine for Chemosuppression of Plasmodium Falciparum

Phase 2

Completed

• Conditions: Malaria
• Interventions: Drug: Placebo; Drug: Tafenoquine 25mg; Drug: Tafenoquine 50mg; Drug: Tafenoquine 100 mg; Drug: Mefloquine 250 mg; Drug: Tafenoquine 200 mg

• Registration Number: NCT02488902
• Lead Sponsor: U.S. Army Medical Research and Development Command

Brief Summary

This was a randomised, double-blind, placebo-controlled study to compare the efficacy of a range four weekly doses of tafenoquine, and weekly mefloquine, with placebo as chemosuppression of P. falciparum malaria. Medications and placebo were matched and a double-dummy technique enabled blinding of tafenoquine versus mefloquine.

Detailed Description

Not available

Study Timeline

• Study Start: 1998-08
• Primary Completion: 1998-09
• Study Completion: 2003-03
• Study First Submitted: 2015-06-30
• Study First Submitted QC: 2015-06-30
• Study First Posted: 2015-07-02
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-12
• Last Update Posted: 2018-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 521

Inclusion Criteria

• Willing subjects in good general health.

  • Males aged 18 to 60; females aged 50 to 60.
  • Subjects who planned to stay in the study area until the end of the study.

Exclusion Criteria

• Subjects with any cardiovascular, liver, neurologic, or renal function abnormality which, in the opinion of the clinical investigators, would have placed them at increased risk of an adverse event or confused the result.

  • Subjects with a personal or family history of seizures or frank psychiatric disorder.
  • Females who had not ceased menstruation; a urine β-human chorionic gonadotrophin (β-HCG) test was to be performed at screening females who had ceased menstruation to exclude pregnancy as a cause.
  • Females who were lactating.
  • Subjects given antimalarial drugs for treatment within two weeks of study drug initiation.
  • Subjects with clinically significant abnormalities (to include but not limited to abnormal hepatic or renal function) as determined by history, physical and routine blood chemistry and haematology values.
  • Subjects with known hypersensitivity to any of the study drugs.
  • Subjects unwilling to remain in the area, report for drug administration or blood drawing during the 3-4 month duration of the study.
  • Subjects with G6PD deficiency (as determined by two separate qualitative tests per subject administered using distinct methods; methods used were visual dye and filter paper methods).
  • Subjects with any of the following laboratory values: haemoglobin (Hb) <8g/dL, platelets <80,000/mm3, white blood cell count (WBC) <3000/mm3, creatinine >1.5mg/dL, alanine transaminase (ALT) >60IU or 1+ haematuria as detected by urine dipstick.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose.
Tafenoquine 25mg	Tafenoquine 25mg	Tafenoquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose.
Tafenoquine 50mg	Tafenoquine 50mg	Tafenoquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose.
Tafenoquine 100 mg	Tafenoquine 100 mg	Tafenoquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose.
Mefloquine 250 mg	Mefloquine 250 mg	Mefloquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose.
Tafenoquine 200 mg	Tafenoquine 200 mg	Tafenoquine was administered initially as a loading course of one capsule daily for 3 days, followed by a weekly dosing regimen at the same dose.

Primary Outcome Measures

Name	Time	Method
First occurrence of malaria infection	16 weeks	First occurrence of malaria infection as documented by a positive malaria smear.

Secondary Outcome Measures

Name	Time	Method
Time to confirmation of parasitaemia	16 weeks	Time to confirmation of parasitaemia as documented by two consecutive positive smears and the incidence density of parasitaemia.