Open-label study to evaluate safety, tolerability, potential pharmacokinetic interactions and mosquito-lethal effects of orally administered ivermectin, primaquine, dihydroartemisinin-piperaquine, and albendazole in healthy adult subjects
The primary objective of this project is to evaluate the safety and tolerability of co-administered single dose dihydroartemisinin-piperaquine (DHA-PPQ), ivermectin (IVM), primaquine (PQ), and albendazole (ABZ) in healthy subjects.
The secondary objectives are:
- To characterize the potential pharmacokinetic interactions between DHA-PPQ, IVM, PQ, and ABZ in healthy adult subjects.
- To characterize the pharmacokinetic properties of PQ (and its major metabolite), DHA-PPQ, IVM, and ABZ (and its major metabolite) when given alone and in combination.
- To investigate pharmacogenetic polymorphisms affecting drug levels of PQ, DHA-PPQ, IVM, ABZ and their metabolites.
- To determine mosquito lethal efficacy of IVM, PQ, ABZ, and DHA-PPQ combinations against Anopheles dirus and Anopheles minimus.
- To determine if IVM concentrations in venous blood differ from capillary blood.
Brief title: Pharmacokinetic and mosquito-lethal effects of ivermectin (IVM), primaquine (PQ), dihydroartemisinin-piperaquine (DHA-PPQ) and albendazole (ABZ) in healthy subjects. Ivermectin for Malaria in Southeast Asia (IMSEA)
Currently, in the Greater Mekong Subregion, mass drug administrations (MDAs) with dihydroartemisinin-piperaquine and primaquine are being conducted with the goal of local elimination of all falciparum malaria parasites. Ivermectin MDAs in West Africa reduced Anopheles gambiae survivorship and the proportion of P. falciparum-infectious An. gambiae. Preliminary lab studies illustrated that important GMS malaria vectors are susceptible to ivermectin. Thus ivermectin could be incorporated in MDAs with dihydroartemisinin-piperaquine and primaquine. However, before large-scale deployment in MDAs, the safety and tolerability of these drugs must be evaluated. This clinical trial is a sequential trial in healthy Thai adult volunteers to assess the safety, tolerability, pharmacokinetic interaction, and mosquito-lethal efficacy of ivermectin, dihydroartemisinin-piperaquine, and primaquine.
Dose (ivermectin): 400 μg/kg
- Primary outcome: number of participants with adverse events (timeframe 1.5 years)
- Secondary outcomes: Area under the concentration-time curve AUC(0-∞), Area under the concentration-time curve AUC(0-last), Cmax, elimination clearance, terminal elimination half-life, apparent volume of distribution, pharmacogenetic polymorphisms in case of abnormal drug level, pharmacokinetic differences of AUC(0-∞) for IVM between venous and capillary blood, pharmacokinetic differences of AUC(0-last) between venous and capillary blood, pharmacokinetic differences of Cmax between venous and capillary blood and mosquito survivorship.
ClinicalTrials.gov Identifier: NCT02568098
|Study Type :||Interventional (Clinical Trial)|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|