A FIH Study to Investigate the Safety, Tolerability and PK of P218
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The First in Human (FIH) study is separated into two parts:

        -  The first part is a Single Ascending Dose (SAD), double-blinded, randomized and
           placebo-controlled, including 8 cohorts of 8 subjects (2 placebo and 6 on active drug).

        -  The second part is a food effect cohort with an open-labelled, randomized fed/fasted
           cross-over design.

      The main objectives of the study are to confirm safety, tolerability and Pharmacokinetics
      (PK) of P218 in healthy volunteers.
    

Detailed description: 
      The study is divided into two parts:

      Part A

      This is a double-blind randomised, placebo-controlled, parallel group, ascending dose study
      and will comprise up to eight fasted cohorts (8 volunteers in each) that will receive a
      single ascending dose (SAD) of P218 to assess its safety, tolerability and pharmacokinetic
      profile. Each subject will participate in only one dose group and will receive only one dose
      of study drug. In each cohort, 2 and 6 subjects will be randomized to placebo and P218,
      respectively. The data obtained from each cohort will undergo a formal review by the Safety
      Review Team (SRT). SRT will confirm that it is safe to proceed with the next dose/cohort.

      Part B

      This is the pilot food effect evaluation. Once predicted human efficacious concentrations of
      P218 and a safe exposure window (at least 3-fold above the targeted therapeutic exposure in
      order to account for a possible increase in exposure with food) has been achieved in Part A,
      a new cohort of 8 subjects (all receiving active drug) will be evaluated for food effect in
      an open-label, randomized fed/fasted crossover design. Subjects participating in this food
      effect cohort will be randomized to two single dose sessions (fed/fasted). The second dose
      will be administered after a washout period of at least 5x observed human half-life (T1/2),
      to be confirmed once PK data are available from the relevant doses from Part A.

      Primary objectives:

        -  To investigate the safety and tolerability of single escalating oral doses of P218 when
           administered to healthy volunteers (men and Women of Non Child Bearing Potential
           (WNCBP)) under fasted conditions.

      Secondary objectives:

        -  To describe the pharmacokinetics of P218 and its major glucuronide metabolite (P218 acyl
           glucuronide) in healthy volunteers (men and WNCBP) after administration of single
           escalating oral doses

        -  To investigate the effect of a high fat meal on the pharmacokinetics and
           safety/tolerability of P218.

      This study incorporates the use of an adaptive design. All anticipated dosing levels can be
      adjusted in accordance with PK, safety and tolerability data collected up to the decision
      making time-point.
    

Intervention name(s): Oral administration of P218 capsules; Oral administration of P218 matching placebo
Intervention type(s): Drug; Drug
Intervention description(s): Oral administration of P218 capsules. The number of capsules is determined by the dose level of the cohort.; Oral administration of P218 matching placebo. The number of capsules is identical to the corresponding number of P218 capsules administered to the volunteers on the investigational drug.
Allocation: Randomized
Intervention model: Sequential Assignment
Intervention model description: Part A of the study was conducted as a dose escalation, and that Part B utilized a cross-over design.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment