Determine the Tolerability and Safety of Atovaquone-proguanil (ATV-PG) Co-administered With Amodiaquine (AQ)
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The aim of the study is to determine the tolerability and safety of ATV-PG + AQ, ATV-PG + AQ
      placebo, ATV-PG placebo + AQ, and ATV-PG placebo + AQ placebo administered once daily for 3
      days to healthy adult male and female subjects.This study in healthy adults is the first step
      towards establishing the tolerability and safety of the approved doses of ATV-PG and AQ when
      co-administered. If considered acceptable based on the findings of this study, the
      tolerability, safety and PE will subsequently be assessed, within the target geographical
      areas.
    

Detailed description: 
      Although the tolerability and safety of ATV-PG and AQ alone are well established, additive
      tolerability signals are possible on co-administration. Four treatment arms will be used:
      ATV-PG + AQ placebo, ATV-PG placebo + AQ, ATV-PG placebo + AQ placebo, as well as ATV-PG +
      AQ. This will facilitate discrimination of the contribution of the treatments to any
      tolerability signal. In the event that ATV-PG + AQ is not considered sufficiently well
      tolerated, data on the individual agents will provide an indication of whether ATV-PG or AQ
      are suitable partner drugs for other combinations.

      Thus, this study will evaluate in healthy adults, whether the tolerability and safety profile
      of once daily administration of ATV-PG + AQ for 3 days supports future use in Seasonal
      Malaria Chemoprevention (SMC), which will entail administration on a monthly basis to an
      apparently healthy population of children of 3 months of age and older, for the duration of
      the malaria season.

      This study will also determine the pharmacokinetics of ATV, PG, CG (active metabolite of PG),
      AQ and DEAQ (active metabolite of AQ).

      Given the ultimate target population (children in Southern and Easter Africa in areas in
      which SMC with SPAQ is not currently deployed due to SP resistance), the study will be
      carried out in healthy subjects of sub-Saharan African origin (defined as subjects whose
      parents were both born in sub-Saharan Africa).
    

Intervention name(s): ATV-PG 1000-400 mg + AQ 612 mg
Intervention type(s): Drug
Intervention description(s): The dosing will be carried out by an unblinded member of the investigator's staff. Dosing will take place behind a curtain and during IMP administration the subjects will be blindfolded. ATV-PG (or placebo) will always be given first, then AQ (or placebo).
Other intervention name(s): ATV-PG 1000-400 mg + AQ unmatched placebo; ATV-PG unmatched placebo + AQ 612 mg
Allocation: Randomized
Intervention model: Factorial Assignment
Intervention model description: Fifty-two subjects will be enrolled and randomized to one of the four treatment (Cohorts 1 to 4) in a ratio of 4:3:3:3 as described below:
Treatment 1 (n=16) - ATV-PG 1000-400 mg + AQ 612 mg;
Treatment 2 (n=12) - ATV-PG 1000-400 mg + AQ unmatched placebo;
Treatment 3 (n=12) - ATV-PG unmatched placebo + AQ 612 mg;
Treatment 4 (n=12) - ATV-PG unmatched placebo + AQ unmatched placebo.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention