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

A Randomized, Double-blind, Placebo-controlled Evaluation of Increasing Doses of Weekly Tafenoquine for Chemosuppression of Plasmodium Falciparum in Semi-immune Adults Living in the Kassena-Nankana District of Northern Ghana

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.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Drug: Placebo; Drug: Tafenoquine 25mg; Drug: Tafenoquine 50mg; Drug: Tafenoquine 100 mg; Drug: Tafenoquine 200 mg; Drug: Mefloquine 250 mg

• Study Type: Interventional
• Enrollment (Actual): 521
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Placebo; Placebo
Experimental: 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.	Drug: Tafenoquine 25mg; Tafenoquine 25mg
Experimental: 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.	Drug: Tafenoquine 50mg; Tafenoquine 50mg
Experimental: 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.	Drug: Tafenoquine 100 mg; Tafenoquine 100 mg
Experimental: 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.	Drug: Tafenoquine 200 mg; Tafenoquine 200 mg
Experimental: 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.	Drug: Mefloquine 250 mg; Mefloquine 250 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
First occurrence of malaria infection	First occurrence of malaria infection as documented by a positive malaria smear.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to confirmation of parasitaemia	Time to confirmation of parasitaemia as documented by two consecutive positive smears and the incidence density of parasitaemia.	16 weeks

Collaborators and Investigators

• Sponsor: U.S. Army Medical Research and Development Command
• Collaborators: SmithKline Beecham
• Investigators: Principal Investigator: Braden Hale, MD, US Naval Medical Research Unit

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: August 1, 1998
• Primary Completion (Actual): September 1, 1998
• Study Completion (Actual): March 1, 2003

Study Registration Dates

• First Submitted: June 30, 2015
• First Submitted That Met QC Criteria: June 30, 2015
• First Posted (Estimate): July 2, 2015

Study Record Updates

• Last Update Posted (Actual): September 13, 2018
• Last Update Submitted That Met QC Criteria: September 12, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Anti-Infective Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Mefloquine; Tafenoquine
• Other Study ID Numbers: A-8340