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

United States Army Medical Research and Development Command (USAMRDC)

Status and phase: Completed; Phase 2

Conditions: Malaria

Treatments: Drug: Mefloquine 250 mg; Drug: Tafenoquine 25mg; Drug: Placebo; Drug: Tafenoquine 100 mg; Drug: Tafenoquine 50mg; Drug: Tafenoquine 200 mg

Study type: Interventional

Funder types: Other U.S. Federal agency; Industry

Identifiers

NCT02488902

A-8340

Details and patient eligibility

About

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.

Enrollment: 521 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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521 participants in 6 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Tafenoquine 25mg

Experimental group

Description:

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.

Treatment:

Drug: Tafenoquine 25mg

Tafenoquine 50mg

Experimental group

Description:

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.

Treatment:

Drug: Tafenoquine 50mg

Tafenoquine 100 mg

Experimental group

Description:

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.

Treatment:

Drug: Tafenoquine 100 mg

Tafenoquine 200 mg

Experimental group

Description:

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.

Treatment:

Drug: Tafenoquine 200 mg

Mefloquine 250 mg

Experimental group

Description:

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.

Treatment:

Drug: Mefloquine 250 mg