A new fixed dose artesunate (AS)/mefloquine (MQ) was assessed in adults, hospitalized for 28 days, with uncomplicated, drug resistant falciparum malaria. Patients (n=25/arm) were treated with: (i) two fixed dose tablets (AS/MQ arm: AS 100 mg/MQ 200 mg/tablet) daily for 3 days (D0, 1, 2) or (ii) non fixed AS (AS+MQ arm: 4 mg/kg/d x 3d) + MQ (15 mg/kg D1, and 10 mg/kg D2), dosed by weight. Clinical, laboratory, ECG adverse events (AEs), efficacy, pharmacokinetic parameters were assessed over 28 days. Both regimens were well tolerated. No AEs were drug related. Two serious AEs, malaria induced hypotension occurring in the AS/MQ arm, necessitated rescue treatment. There were no significant changes in hematology, biochemistry, PR and QRS intervals. For all patients, mean Fridericia corrected QT intervals were significantly (p < 0.0027) prolonged on D3 (407 ms) and D7 (399 ms) vs. D0 (389 ms) in parallel with significant (p < 0.0003) falls in heart rates [67 (D3), 73 (D7), 83 (D0) beats/minute]. Fixed-non fixed formulations were bioequivalent for MQ but not for AS and DHA. One AS/MQ patient developed a new infection on D28; his D28 plasma MQ concentration was 503.8 ng/mL. Fixed dose AS/MQ was well tolerated, had broadly similar PK profiles to non fixed AS+MQ and is a suitable replacement.
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