Conditions: Malaria
Keywords: pharmacokinetics safety tolerability bioavailability
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 24
Healthy volunteers: yes

Brief summary:
Piperaquine tablets (coated) + OZ439 granules + TPGS granules will be co-administered in Phase IIb (adults). However, safety and PK data (for OZ439 plus piperaquine) were obtained using piperaquine tablets plus OZ439 as Powder in Bottle with milk. Piperaquine has not yet been administered together with TPGS. Co-administration of piperaquine plus OZ439 as Powder in Bottle (PIB) with milk results in an increase in OZ439 exposure (current estimate \~ 70% due to a small drug drug interaction).

This study investigates the exposure of piperaquine and OZ439 when co-administered as piperaquine phosphate tablets and OZ439 + TPGS prototype (a formulation close to that of Phase IIb, but not identical), in order to select the appropriate doses for Phase IIb. The reference treatment is piperaquine phosphate tablets + OZ439 Powder in Bottle + full fat milk

Detailed description:
Objectives:

1. To evaluate the piperaquine and OZ439 pharmacokinetics when administered as a combination of piperaquine phosphate tablets with OZ439 / TPGS formulation in the fasted state
2. To evaluate the piperaquine and OZ439 pharmacokinetics of a reference free combination formulation: piperaquine phosphate tablets with OZ439 powder in bottle (PIB) given with full fat milk
3. To determine safety and tolerability of OZ439 and piperaquine phosphate when co-administered.

Arms:
arm 1: PQP tablets 1440mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted. arm 2: PQP tablets 960mg and OZ439+TPGS 800mg co-administered as a single oral dose fasted. arm 3: PQP Tablets 1440 mg and OZ439 PIB 800mg + full fat cow's milk

Interventions: intervention 1: PQP tablets 960mg intervention 2: PQP tablets 1440mg intervention 3: OZ439+TPGS 800mg intervention 4: OZ439 PIB 800mg
Intervention descriptions: intervention 1: Piperaquine phosphate tablets 960mg intervention 2: Piperaquine phosphate tablets 1440mg intervention 3: OZ439+TPGS prototype formulation 800mg intervention 4: OZ439 Powder in Bottle Aqueous Solution 800mg

Protocol document: