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

NCT02488902 | Completed Phase 2

• 1 other identifier: A-8340
• Study Type: interventional
• Target: 521
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Malaria

Outcome Measures

Primary Outcomes (1)

• First occurrence of malaria infection

  First occurrence of malaria infection as documented by a positive malaria smear.

  16 weeks

Secondary Outcomes (1)

• Time to confirmation of parasitaemia

  16 weeks

Study Arms (6)

Placebo

PLACEBO COMPARATOR

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

Tafenoquine 25mg

EXPERIMENTAL

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 50mg

EXPERIMENTAL

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 100 mg

EXPERIMENTAL

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 200 mg

EXPERIMENTAL

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

Mefloquine 250 mg

EXPERIMENTAL

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

Interventions

Placebo DRUG

Placebo

Placebo

Tafenoquine 25mg DRUG

Tafenoquine 25mg

Tafenoquine 25mg

Tafenoquine 50mg DRUG

Tafenoquine 50mg

Tafenoquine 50mg

Tafenoquine 100 mg DRUG

Tafenoquine 100 mg

Tafenoquine 100 mg

Tafenoquine 200 mg DRUG

Tafenoquine 200 mg

Tafenoquine 200 mg

Mefloquine 250 mg DRUG

Mefloquine 250 mg

Mefloquine 250 mg

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• SmithKline Beecham: collaborator

Related Publications (1)

• 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.

  PMID: 28495354 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

tafenoquine; Mefloquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Braden Hale, MD

  US Naval Medical Research Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2015
• First Posted: July 2, 2015
• Study Start: August 1, 1998
• Primary Completion: September 1, 1998
• Study Completion: March 1, 2003
• Last Updated: September 13, 2018

Record last verified: 2018-09