First-in-Human Study to Assess the Safety, Tolerability and Pharmacokinetics of MMV367
Condition: Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      This three-part, first-in-human, healthy volunteer study aims to assess the safety and
      tolerability of the test medicine as well as how it is taken up by the body when given as
      single and multiple doses. The effect of food on the test medicine will also be investigated.

      In Part 1, up to 40 volunteers will be split into up to 5 groups and will receive single oral
      doses of the test medicine or dummy medicine (placebo), at different dose levels.

      In Part 2, up to 8 volunteers will receive one oral dose of the test medicine in the fed
      state and one oral dose in the fasted state.

      In Part 3, up to 24 volunteers will be split into up to 3 groups and will receive single oral
      daily doses of the test medicine or placebo for 3 consecutive days.

      Volunteers' blood and urine will be taken throughout the study for analysis of the test
      medicine and for their safety. In Part 1 and Part 3, volunteers will be discharged from the
      clinical unit 4 days after the final dose of the test medicine and will return to the
      clinical unit on two occasions for safety assessments to be performed. In Part 2, volunteers
      will be discharged from the clinical unit 4 days after the final dose of the test medicine
      and will return to the clinical unit on a single occasion for safety assessments to be
      performed. Volunteers are expected to be involved in this study for approximately 6 weeks for
      all study parts, from screening to the final return visit.
    

Detailed description: 
      Part 1 will be a double-blinded, randomised, placebo-controlled, single ascending dose (SAD)
      study, which will comprise up to 5 fasted cohorts (Cohorts 1A to 1E; Cohort 1E will be
      optional), with 8 participants in each cohort. Participants will be randomly assigned to
      receive a single oral dose of either active IMP (investigational medicinal product) (6
      participants) or placebo (2 participants) to assess its safety, tolerability and PK
      (pharmacokinetic) profile. Each participant will take part in one cohort. Cohort A dose is
      100mg. Doses for cohorts B to E will be determined following a blinded interim review of the
      safety, tolerability and PK data after each cohort, prior to the dose decision for subsequent
      cohorts.

      Part 2 will be an open-label, randomised, balanced two-period crossover, food effect
      evaluation. It is planned to enrol 8 participants. In Period 1, participants will be
      randomised to 1 of 2 treatment sequences. If a participant is randomised to receive MMV367 in
      the fasted state in Period 1, they will receive MMV367 in the fed state in Period 2 and vice
      versa. The dose administered in Part 2 will be determined once predicted human therapeutic
      concentrations of MMV367 and a safe exposure window has been established in Part 1.

      Part 3 will be a double-blinded, randomised, placebo-controlled, multiple-dose study. A total
      of 8 participants per cohort (A-C) will receive once-daily doses of MMV367 (6 participants)
      or placebo (2 participants) for 3 days, in the fasted state, to assess safety, tolerability
      and PK profile of multiple dosing. Cohorts 3B and 3C are optional and may proceed after a
      review of the safety and PK data. The dose(s) administered in Part 3 will be determined after
      review of the data from Part 1.

      Parts 1 and 3 will follow a sentinel dosing design. For each of the three parts, participants
      will be screened within 28 days prior to first admission to the clinical unit on the morning
      of Day -1.

      Part 1: In each cohort, participants will be dosed on Day 1 and will remain resident in the
      clinical unit until discharge on Day 5. They will attend the clinical unit for a return visit
      on Day 7 and again on Day 15 for end of study assessments.

      Part 2: Participants will be dosed on Day 1 (Period 1 dose) and on Day 8 (Period 2 dose) and
      will remain resident in the clinical unit until discharge on Day 12. They will attend the
      clinical unit on Day 14 for end of study assessments. Based on emerging PK data from Part 1,
      the washout period between the Period 1 and Period 2 doses may be extended.

      Part 3: Participants will receive a single dose on Days 1, 2 and 3 and will remain resident
      in the clinical unit until discharge on Day 7. They will attend the clinical unit for a
      return visit on Day 9 and again on Day 17 for end of study assessments.

      For all parts, blood samples will be collected at regular intervals for PK analysis and
      safety from Day 1 to discharge from the study.
    

Intervention name(s): MMV367; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Single dose dispersed in sterile water.; Single dose dispersed in sterile water.
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Malaria; Healthy Volunteers