A Phase 1 Study to Assess the Safety, Tolerability, and Pharmacokinetic Profile of a Single Doses of MMV533.

Phase 1

Completed

Conditions: Malaria

Interventions: Drug: MMV688533

Registration Number: NCT04323306

Lead Sponsor: Medicines for Malaria Venture

Brief Summary: Phase 1, single -centre study in 2 parts. The study designs for each part are well established for first-in-human studies and are appropriate to assess safety, tolerability and preliminary pharmacokinetics.

Detailed Description: Part 1:

Double-blind, randomized, placebo-controlled, sequential ascending single dose study in healthy adult participants, 7 cohorts, and 1 additional cohort may be considered if needed according to the observed safety, tolerability, and pharmacokinetics results.

A sentinel dosing strategy will be implemented at each dose level to ensure the best conditions of safety. Each cohort will be divided into at least 2 subgroups. The first group (sentinel cohort) will include 2 participants that will be dosed on the first day, with 1 participant receiving MMV533 and 1 participant receiving placebo. The safety and tolerability data from the sentinel cohort up to and including 96 hours post-dose will be reviewed by the Principal Investigator, the Medical Monitor and the Sponsor´s Medical Director. Following a satisfactory safety review, dosing of the remaining participants in the cohort may proceed.

Part 2:

Open label, 2-period cross-over, randomized, pilot food effect study to provide preliminary information on the effect of a high-fat meal on the pharmacokinetics of a single-dose oral administration of MMV533 to healthy male and female participants aged between 18-55 years old. Part 2 may be conducted in parallel to or after completion of Part 1 at the discretion of the SRC. The dose will be selected by the SRC based on PK and safety results obtained in Part 1 and also taking into account the human efficacious dose/exposure predicted from preclinical efficacy studies in rodent malaria models.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 72

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2 SAD	MMV688533	Single ascending dose to be determined after SRC review of previous cohort.
Cohort 5 SAD	MMV688533	Single ascending dose to be determined after SRC review of previous cohort.
Cohort 1 SAD	MMV688533	5 mg MMV533 with single ascending dose
Cohort 6 SAD	MMV688533	Single ascending dose to be determined after SRC review of previous cohort.
Cohort 4 SAD	MMV688533	Single ascending dose to be determined after SRC review of previous cohort.
Cohort 7 SAD	MMV688533	Single ascending dose to be determined determine after SRT review of previous cohort. Dose will not exceed 400 mg.
Part 2: Food Effect	MMV688533	Open label, 2-period cross-over, randomized, pilot food effect study to provide preliminary information on the effect of a high-fat meal on the pharmacokinetics of a single-dose oral administration of MMV533 determined to be safe in Part 1.
Cohort 3 SAD	MMV688533	Single ascending dose to be determined after SRC review of previous cohort.

Primary Outcome Measures

Name	Time	Method
The Tolerability and Safety of Ascending Single Oral Doses of MMV533	Part 1 is 28 days post IMP and for Part 2, 21 days post IMP administration	Vital signs: body temperature. Change from baseline.

Secondary Outcome Measures