Clinical effectiveness of previous regimens to treat Plasmodium vivax infection have been hampered by compliance. A study has assessed the dose-response, safety, and tolerability of single-dose Tafenoquine plus 3-day Chloroquine for Plasmodium vivax malaria radical cure.
In this double-blind, randomised, dose-ranging phase 2b study ( DETECTIVE ), men and women ( aged 16 years or more ) with microscopically confirmed Plasmodium vivax monoinfection ( parasite density greater than 100 to less than 100 000 per mcL blood ) were enrolled from community health centres and hospitals across seven sites in Brazil, Peru, India, and Thailand.
Patients with glucose-6-phosphate dehydrogenase enzyme activity of less than 70% were excluded.
Eligible patients received Chloroquine ( days 1-3 ) and were randomly assigned ( 1:1:1:1:1:1 ) by a computer-generated randomisation schedule to receive single-dose Tafenoquine 50 mg, 100 mg, 300 mg, or 600 mg, Primaquine 15 mg for 14 days, or Chloroquine alone.
Randomisation was stratified by baseline parasite count ( less than or equal to 7500 and greater than 7500 per mcL blood ).
The primary efficacy endpoint was relapse-free efficacy at 6 months from initial dose ( ie, clearance of initial infection without subsequent microscopically confirmed infection ), analysed by intention to treat.
During the period 2011-2013, 329 patients were randomly assigned to a treatment group ( Chloroquine plus Tafenoquine 50 mg [ n=55 ], 100 mg [ n=57 ], 300 mg [ n=57 ], 600 mg [ n=56 ]; or to Chloroquine plus Primaquine [ n=50 ]; or Chloroquine alone [ n=54 ] ).
Relapse-free efficacy at 6 months was 57.7% with Tafenoquine 50 mg, 54.1% with Tafenoquine 100 mg, 89.2% with Tafenoquine 300 mg, 91.9% with Tafenoquine 600 mg, 77.3% with Primaquine, and 37.5% with Chloroquine alone.
Tafenoquine 300 mg and 600 mg had better efficacy than Chloroquine alone ( treatment differences 51.7%, p less than 0.0001, with Tafenoquine 300 mg and 54.5%, p less than 0.0001, with Tafenoquine 600 mg ), as did Primaquine ( treatment difference 39.9%, p=0.0004 ).
Adverse events were similar between treatments. 29 serious adverse events occurred in 26 ( 8% ) of 329 patients; QT prolongation was the most common serious adverse event ( 11 [ 3% ] of 329 ), occurring in five ( 2% ) of 225 patients receiving Tafenoquine, four ( 8% ) of 50 patients receiving Primaquine, and two ( 4% ) of 54 patients receiving Chloroquine alone, with no evidence of an additional effect on QT of Chloroquine plus Tafenoquine coadministration.
In conclusion, single-dose Tafenoquine 300 mg coadministered with Chloroquine for Plasmodium vivax malaria relapse prevention was more efficacious than Chloroquine alone, with a similar safety profile. ( Xagena )
Llanos-Cuentas A et al, The Lancet 2014; 383: 1049-1058