Table 1 Key clinical studies
From: The story of artesunate–mefloquine (ASMQ), innovative partnerships in drug development: case study
Country | Study type | Phase | n | Primary objective | Major findings |
|---|---|---|---|---|---|
Thailand | HNV, PK and tolerability | 1 | 24 | PK and bio-availability of AS and MQ; administered separately and as a coformulation to healthy volunteers and patients | No difference was seen in the bio-equivalence of MQ in the two formulations; although a difference was seen for AS/DHA, this was not concluded to be clinically relevant[20] |
PK, efficacy and safety | 2 | 50 | Population PK model of new dosage regime of MQ with AS in loose combination over three days | Splitting the 25 mg/kg dose of MQ into three doses of 8 mg/kg improved oral bio-availability compared to the conventional split-dose regimen results. New regimen was well tolerated and with an equivalent therapeutic response[21] | |
PK, efficacy and safety | 2b | 50 | Safety and PK of ASMQ FDC vs non-fixed AS+MQ against multi-drug resistant falciparum malaria in adults | FDC well-tolerated with broadly similar PK profiles to non-fixed AS plus MQ[22]. The observed slowing of heart rate was best explained by malaria resolution[23] | |
Efficacy and safety | 3 | 500 | ASMQ FDC with separate tablets in adults and children with uncomplicated multidrug-resistant falciparum malaria | Cure rates were 91.9% for the FDC after 63 days, with a lower incidence of vomiting compared to those in the loose tablets group[24] | |
Myanmar | Competitive Effectiveness | 4 | 808 | Effectiveness of five artemisinin combination regimens with or without PQ in uncomplicated falciparum malaria | ASMQ provided the greatest post-treatment suppression of malaria after 63 days, with the addition of PQ substantially reducing transmission potential of malaria[25] |
India | Efficacy and safety | 3 | 77 | PCR corrected cure rate of ASMQ FDC in adult patients with uncomplicated falciparum malaria | Mean parasite clearance time of 48 hours |
Brazil | Intervention study: PK Efficacy and safety | 3b/4 | 23,845 | Effectiveness of ASMQ FDC in reducing malaria transmission in the Juruá valley | Early detection of malaria and treatment with ASMQ FDC was feasible and efficacious, significantly reduced the incidence and morbidity of falciparum malaria[26] |