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First-in-Human Study of SRT-015 in Healthy Subjects.

Phase 1
Completed
Conditions
Nonalcoholic Steatohepatitis
Interventions
Other: Matching Placebo for SRT-015
Registration Number
NCT04887038
Lead Sponsor
Syneos Health
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
81
Inclusion Criteria
  1. Males or females aged 18 to 45 years of age with a BMI >18.0 and <32.0 kg/m2 and body weight greater than or equal to 50kg for males and greater than or equal to 45 kg for females.
  2. Casual smoker (defined by the consumption of no more than 5 cigarettes per week, and willing to abstain from the consumption of cigarettes and related products for the study duration) or non smoker.
  3. Agree to use appropriate contraception.

Key

Exclusion Criteria
  1. Any clinically significant abnormality at physical examination, clinically significant abnormal laboratory test results (liver function tests must be strictly within normal ranges) or positive test for HIV, hepatitis B, or hepatitis C found during medical screening.
  2. Positive urine drug screen or alcohol breath test at screening and check-in (Day -1).
  3. Positive pregnancy test, or breast feeding.
  4. Clinically significant 12-lead ECG abnormalities.
  5. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Matching Placebo for SRT-015Matching Placebo for SRT-015-
Drug :SRT-015SRT-015Experimental, Single and Multiple Oral escalating dose and Food Effect Cohort
Primary Outcome Measures
NameTimeMethod
3. To evaluate maximum serum concentration of SRT-015 following single and multiple oral dose administration in healthy subjects (Cmax)Up to two weeks

Maximum serum concentration (mg/L)

To evaluate the safety and tolerability following of single and multiple oral doses of SRT-015 in healthy subjectsUp to two weeks

Number of participants with serious and other non-serious adverse events

To evaluate the exposure to SRT-015 following single and multiple oral dose administration in healthy subjects (AUC last)Up to two weeks

Area under the serum concentration-time curve from time zero to last measurable concentration (mg\*h/L)

Secondary Outcome Measures
NameTimeMethod
To compare the exposure to SRT-015 (AUClast) in capsule formulation vs suspension formulation and fed vs fasted stateUp to two weeks

Comparison of the area under the serum concentration-time curve from time zero to last measurable concentration after administration of SRT-015 after a meal v in a fasting state (mg\*h/L)

To compare maximum serum concentration of SRT-015 (Cmax) in capsule formulation vs suspension formulation and fed v fasted stateUp to two weeks

Maximum serum concentration (mg/L)

Trial Locations

Locations (1)

Nucleus Network Pty Ltd

🇦🇺

Victor Harbor, Melbourne, Australia

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