Clinical trial NCT02573857
Conditions: Malaria
Keywords: Induced blood stage malaria Transmission Gametocytemia
Sponsor: Medicines for Malaria Venture
Start date: 2015-10-01; Completion date: 2016-05-01
Enrollment: 16 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Part A

-Cohort 1 DSM265 will be administered as a single dose (400 mg). For cohort 1 only, an additional single dose (400 mg) of DSM265 may be given if gametocytemia develops. Treatment with DSM265 will be given after an overnight fasting period of ≥ 8 hours. If dosing is to occur in the evening, subjects will be required to fast for ≥4 hours prior to receiving treatment. Subjects will be required to fast for a further four hours anytime after dosing with DSM265.

Part B

* Cohort 2 OZ439 will be administered as a single 200 mg dose. If recrudescence is observed, a single 400 mg dose of OZ439 will be given. Treatment with OZ439 will be administered after an overnight fasting period of ≥ 6 hours. If dosing is to occur in the evening, subjects will be required to fast for ≥4 hours prior to receiving treatment. Participants will drink 200 mL of milk prior to drug administration, and then swallow the appropriate volume of OZ439 suspension. Subjects will be required to fast for a further six hours anytime after dosing with OZ439.
* Cohort 3 DSM265 will be administered as a single dose (400 mg) as described for cohort 1. No additional dose will be administered.

Detailed description:
This is a single-centre, open label study using induced blood stage malaria (IBSM) infection to assess the effectiveness of the investigational drugs DSM265 or OZ439 in reducing parasitemia. Transmission blocking activity of DSM265 (in P. falciparum infection; cohort 1 only) and infectivity to vector mosquitoes prior to drug treatment (in P. vivax infection; cohort 2 and 3) will also be assessed. This study will be conducted in up to three cohorts (n = 8 per cohort), and will be divided into 2 parts. In Part A (cohort 1) the efficacy of a single administration of 400 mg DSM265 for the clearance of asexual blood stages of P. falciparum will be determined. Activity of a second single dose of 400 mg DSM265 against gametocytes will be assessed in this cohort only if sexual stages are identified by PCR following the initial drug treatment. In Part B, subjects will be infected with P. vivax by IBSM, then treated with a single 200 mg dose OZ439 (cohort 2) or 400 mg dose of DSM265 (cohort 3). For cohort 2, if recrudescence occurs following initial drug treatment with 200 mg OZ439, then affected participants who reach the treatment threshold will receive a single 400 mg dose of OZ439. The PK/PD relationship following drug treatment will be determined in order to further characterize the antimalarial activity of the investigational drug in the IBSM system using P. falciparum (for cohort 1; 400 mg DSM265) or P. vivax (for cohort 2, 200 mg OZ439; cohort 3, 400 mg DSM265).

The treatment effects on gametocytemia (if sexual blood stages are detected by PCR) and transmission blocking activity of DSM265 will be investigated as a secondary objective for cohort 1 (P. falciparum infection). Prior to drug treatment, the infectivity of P. vivax IBSM infection to vector mosquitoes will also be investigated as a secondary objective for Part B, cohorts 2 and 3. The exposures achieved with the doses proposed for DSM265 used in Part A and DSM265 or OZ439 in Part B are associated with a safety profile which is well described from previous studies and significantly below the maximum tolerated exposures reported for either drug.

Arms: arm 1: Cohort 1: the efficacy of a single administration of 400 mg DSM265 for the clearance of asexual blood stages of P. falciparum will be determined. Activity of a second single dose of 400 mg DSM265 against gametocytes will be assessed in this cohort only if sexual stages are identified by PCR following the initial drug treatment. arm 2: Cohort 2: subjects will be infected with P. vivax by IBSM, then treated with a single 200 mg dose OZ439. If recrudescence occurs following initial drug treatment with 200 mg OZ439, then affected participants who reach the treatment threshold will receive a single 400 mg dose of OZ439. arm 3: Cohort 3: subjects will be infected with P. vivax by IBSM, then treated with a single 400 mg dose of DSM265
Interventions: intervention 1: DSM265 intervention 2: OZ439
Intervention descriptions: intervention 1: Oral suspension from bulk powder intervention 2: Oral suspension from powder in a bottle

Protocol documents: