BACKGROUND:Tafenoquine is an analogue of primaquine with an improved therapeutic and safety profile. It has a long half-life and activity against liver-stage malaria parasites, so may be useful for chemoprophylaxis. In this randomised, double-blind study we assessed the efficacy and safety of tafenoquine in different doses. METHODS:2144 individuals aged 12-20 years living in Lambaréné, Gabon, an endemic area for Plasmodium falciparum malaria, were invited to take part. 535 attended, and 426 eligible participants were randomly assigned tafenoquine (250 mg, 125 mg, 62.5 mg, or 31.25 mg) or placebo daily for 3 days. 417 received initial curative treatment with halofantrine, and 410 completed the assigned prophylaxis regimen. During follow-up of 70 days, adverse events were recorded and thick blood smears were examined weekly. The primary and secondary endpoints were the number of individuals with positive blood smears by day 56 and day 77, respectively. Analyses were per-protocol. FINDINGS:Eight positive blood smears were recorded by day 56 (four/82 participants in the placebo group; four/79 tafenoquine 31.25 mg group). By day 77, 34 positive blood smears had been recorded (14/82 placebo; 16/79 tafenoquine 31.25 mg; three/86 tafenoquine 62.5 mg; one/79 tafenoquine 125 mg; none/84 tafenoquine 250 mg). Numbers of adverse events did not differ significantly between the treatment groups. INTERPRETATION:Tafenoquine is effective and well tolerated. It has the potential to replace currently used drugs for malaria chemoprophylaxis.
RCT Entities:
BACKGROUND:Tafenoquine is an analogue of primaquine with an improved therapeutic and safety profile. It has a long half-life and activity against liver-stage malaria parasites, so may be useful for chemoprophylaxis. In this randomised, double-blind study we assessed the efficacy and safety of tafenoquine in different doses. METHODS: 2144 individuals aged 12-20 years living in Lambaréné, Gabon, an endemic area for Plasmodium falciparum malaria, were invited to take part. 535 attended, and 426 eligible participants were randomly assigned tafenoquine (250 mg, 125 mg, 62.5 mg, or 31.25 mg) or placebo daily for 3 days. 417 received initial curative treatment with halofantrine, and 410 completed the assigned prophylaxis regimen. During follow-up of 70 days, adverse events were recorded and thick blood smears were examined weekly. The primary and secondary endpoints were the number of individuals with positive blood smears by day 56 and day 77, respectively. Analyses were per-protocol. FINDINGS: Eight positive blood smears were recorded by day 56 (four/82 participants in the placebo group; four/79 tafenoquine 31.25 mg group). By day 77, 34 positive blood smears had been recorded (14/82 placebo; 16/79 tafenoquine 31.25 mg; three/86 tafenoquine 62.5 mg; one/79 tafenoquine 125 mg; none/84 tafenoquine 250 mg). Numbers of adverse events did not differ significantly between the treatment groups. INTERPRETATION:Tafenoquine is effective and well tolerated. It has the potential to replace currently used drugs for malaria chemoprophylaxis.
Entities:
Keywords:
Africa; Africa South Of The Sahara; Clinical Research; Clinical Trials; Developing Countries; Diseases; Double-blind Studies; Drugs; Examinations And Diagnoses; French Speaking Africa; Gabon; Laboratory Examinations And Diagnoses; Laboratory Procedures; Malaria--prevention and control; Middle Africa; Parasitic Diseases; Research Methodology; Research Report; Studies; Treatment
Authors: Peter E Nasveld; Michael D Edstein; Mark Reid; Leonard Brennan; Ivor E Harris; Scott J Kitchener; Peter A Leggat; Philip Pickford; Caron Kerr; Colin Ohrt; William Prescott Journal: Antimicrob Agents Chemother Date: 2009-12-07 Impact factor: 5.191
Authors: Ann K Miller; Emma Harrell; Li Ye; Sharon Baptiste-Brown; Jőrg-Peter Kleim; Colin Ohrt; Stephan Duparc; Jörg J Möhrle; Alison Webster; Sandra Stinnett; Arlene Hughes; Sandy Griffith; Andrew P Beelen Journal: Br J Clin Pharmacol Date: 2013-12 Impact factor: 4.335
Authors: Bruce G Charles; Ann K Miller; Peter E Nasveld; Mark G Reid; Ivor E Harris; Michael D Edstein Journal: Antimicrob Agents Chemother Date: 2007-05-21 Impact factor: 5.191