Clinical trial NCT02230579
Conditions: Malaria
Keywords: safety tolerability malaria
Sponsor: Medicines for Malaria Venture
Start date: 2014-05-01; Completion date: 2015-02-01
Enrollment: 48 participants; Allocation: RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
This is a first-in-human study of MMV390048. The study will evaluate the safety, tolerability and pharmacokinetic properties of escalating single and multiple doses of MMV390048 when administered to healthy male volunteers and female volunteers of non-childbearing potential.

In addition, the effect of food on the pharmacokinetics and tolerability of MMV390048 will be investigated.

Detailed description:
The study is a single centre, double-blind, randomised, placebo-controlled, ascending dose study in healthy male and female volunteers (of non-childbearing potential) aged 18 to 55 years.

The study will be divided into two parts. The first part will comprise up to seven fasted cohorts (8 to 10 volunteers in each) that will receive a single, ascending dose (SAD) of MMV390048 to assess its safety, tolerability and pharmacokinetic profile. The starting dose administered to the first cohort will be 5 mg. An additional cohort (cohort 8, re-using volunteers from one of the previous cohorts) will receive a single dose of MMV390048 in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability of the compound.

The data obtained from each cohort during the SAD part of the study will undergo a formal review by the Safety Review Team (SRT). Should the safety profile of the compound be deemed acceptable, and the pharmacokinetic parameters indicate that acceptable levels of the drug to elicit a pharmacodynamic response can be achieved in human plasma, the study will then proceed to the second part.

During the second part of the study volunteers will receive multiple, ascending doses (MAD) of MMV390048 to assess the pharmacokinetics, safety and tolerability following multiple oral doses. Up to three cohorts of eight volunteers each will be enrolled into this part of the study. Each volunteer will receive three consecutive daily doses of MMV390048.

Arms: arm 1: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state arm 2: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state arm 3: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state arm 4: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state arm 5: Five fasted cohorts will receive a single, ascending dose of MMV390048. The starting dose will be 5mg. Cohort SAD6 will receive a single dose in a fed state arm 6: Cohort SAD6, reusing volunteers from one of the previous cohorts, will receive a single dose in a fed state to evaluate the effect of food on the pharmacokinetics and tolerability
Interventions: intervention 1: MMV390048 5mg intervention 2: MMV390048 20mg intervention 3: MMV390048 40mg intervention 4: MMV390048 80mg intervention 5: MMV390048 120mg intervention 6: Placebo to match MMV390048
Intervention descriptions: intervention 1: Supplied as "powder in bottle" formulation for reconstitution pre-dose intervention 2: Supplied as "powder in bottle" formulation for reconstitution pre-dose. intervention 3: Supplied as "powder in bottle" formulation for reconstitution pre-dose intervention 4: Supplied as "powder in bottle" formulation for reconstitution pre-dose intervention 5: Supplied as "powder in bottle" formulation for reconstitution pre-dose intervention 6: Supplied as "powder in bottle" formulation for reconstitution pre-dose

Protocol documents: