First-in-Human Study of SRT-015 in Healthy Subjects.
Condition: Nonalcoholic Steatohepatitis
MeSH terms: Fatty Liver; Non-alcoholic Fatty Liver Disease
Study type: Interventional
Phase: Phase 1

Summary: 
      This is phase 1 first-in-human trial evaluating SRT-015 to assess safety, tolerability and
      pharmacokinetics. This study will be conducted in 3 parts - SAD, MAD and Food Effect with
      target of 96 healthy volunteers.

      This will be a single center, Phase 1, randomized, double-blind, placebo controlled, SAD and
      MAD study of dose escalation cohorts evaluating administration of SRT-015 or placebo.
      Additionally, PK will be assessed in fed and fasting states.
    

Detailed description: 
      The study will be divided into three parts:

      Part A: SAD- Randomized, double-blind, placebo-controlled single oral escalating dose of
      SRT-015 or placebo in five cohorts (A1-A5). Each cohort will include 8 healthy subjects (6
      randomized to receive SRT-015 and 2 to receive placebo). Two subjects from each cohort (1 to
      receive SRT-015 and 1 to receive placebo) will be dosed as sentinels, with the remainder of
      the subjects of each cohort (5 to receive SRT-015 and 1 to receive placebo) dosed at least
      the following day.

      An extension cohort (Cohort A6) will allow investigation of a repeat or intermediate dose, at
      the discretion of the Sponsor or Safety Review Committee (SRC).

      Part B: MAD- Randomized, double-blind, placebo-controlled multiple oral escalating dose of
      SRT-015 or placebo in four cohorts (B1-B4). Each cohort will include 8 healthy subjects (6
      randomized to receive SRT-015 and 2 to receive placebo). Subjects will be treated with
      SRT-015 or placebo for 7 days.

      An extension cohort (Cohort B5) will allow investigation of a repeat or intermediate dose at
      the discretion of Sponsor and SRC.

      Part C: Food Effect (FE)- Randomized, crossover oral SRT-015 dose study of 8 healthy adults
      divided into two concurrent groups where half (n=4) of the subjects (Cohort C1) will receive
      the first dose as an oral suspension in fasting state on Day 1 of Period 1, the second dose
      as capsule formulation in fasting state on Day 1 of Period 2 and the third dose as a capsule
      formulation in a fed state on Day 1 of Period 3. The remainder (n=4) of the subjects (Cohort
      C2) will receive the first dose as an oral suspension in fasting state on Day 1 of Period 1,
      the second dose as a capsule formulation in a fed state on Day 1 of Period 2 and the third
      dose as a capsule formulation in a fasting state on Day 1 of Period 3.
    

Intervention name(s): SRT-015; Matching Placebo for SRT-015
Intervention type(s): Drug; Other
Intervention description(s): Each study part (A,B and C) will be completed sequentially, but with partial overlapping. The first cohort of Part B (Cohort B1) may be initiated after safety, tolerability and available PK data are assessed and deemed suitable to continue for a single dose on Part A that is equal to or greater than the total exposure of cohort B1. Part C (Cohort C1 & C2) may be initiated after safety, tolerability and PK data are assessed and deemed suitable to continue for a single dose in part A that is at least double the specified dose from part C.; Matching Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment