Conditions: Malaria Falciparum Malaria Vivax Healthy Volunteers
Keywords: Phase I Safety and tolerability Pharmacokinetic synthetic peroxide trioxolane treatment of erythrocytic stages of malaria
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 63
Healthy volunteers: yes

Brief summary:
OZ439 is a synthetic trioxolane that has potential value as a peroxide antimalarial agent.

This was a Phase I, single-centre, multi-component, double-blind, randomised, placebo-controlled study in healthy male and female subjects. The study was conducted in 3 parts:

* Part A investigated the safety, tolerability and pharmacokinetics (PK) of single oral escalating doses of OZ439. Up to 6 dose levels will be investigated to estimate dose proportionality.
* Part B, the effect of food on a single oral dose of OZ439 was investigated in a 2-way crossover design.
* Part C investigated the safety, tolerability and PK profile of multiple oral doses of OZ439.

The starting oral dose was 50 mg and the maximum single dose to be administered did not exceed 1600 mg per subject. The maximum duration of dosing proposed was 3 days.

Detailed description:

Arms:
arm 1: OZ439 Single doses of 50mg (capsules) arm 2: OZ439 Single doses of 100mg (capsules) arm 3: OZ439 Single doses of 200mg (capsules) arm 4: OZ439 Single doses of 400mg (capsules) arm 5: OZ439 Single doses of 400mg (capsules) administered with food. arm 6: OZ439 Single doses of 400mg (aqueous dispersion) arm 7: OZ439 Single doses of 800mg (capsules) arm 8: OZ439 Single doses of 800mg (aqueous dispersion) arm 9: OZ439 Single doses of 1200mg (capsules) arm 10: OZ439 Single doses of 800mg (aqueous dispersion) arm 11: Placebo control for Single rising Part A arm 12: Single dose of OZ439 800mg aqueous dispersion administered under fed conditions arm 13: Single dose of OZ439 800mg aqueous dispersion administered under fast conditions arm 14: 200mg aqueous solution OZ439 or placebo once daily for 3 days fasted arm 15: 400mg aqueous solution OZ439 or placebo once daily for 3 days fasted arm 16: 800mg aqueous solution OZ439 or placebo once daily for 3 days fasted arm 17: Placebo control for Multiple rising Part C

Interventions: intervention 1: OZ439 50mg API capsules intervention 2: OZ439 200mg API capsules intervention 3: OZ439 400mg aqueous dispersion intervention 4: OZ439 800mg aqueous dispersion intervention 5: OZ439 100mg API capsules intervention 6: OZ439 400mg API capsules intervention 7: OZ439 1600mg aqueous dispersion intervention 8: OZ439 800mg API capsules intervention 9: OZ439 1200mg API capsules intervention 10: Placebo intervention 11: OZ439 200mg aqueous dispersion
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: OZ439 100mg (2x50mg API capsules) intervention 6: OZ439 400mg (2x200mg API capsules) intervention 7: None intervention 8: OZ439 800mg (4x200 API capsules) intervention 9: OZ439 1200mg (6x200mg API capsules) intervention 10: None intervention 11: None

Protocol document: