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

Nonalcoholic Steatohepatitis Clinical Trial

Official title:

A Single and Multiple Dose-escalation First-in-human With Food-effect Study Evaluating the Safety, Tolerability and Pharmacokinetics of SRT-015 Administered Orally.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04887038
• Other study ID #: SRT015-01
• Status: Completed
• Phase: Phase 1
• Start date: May 3, 2021
• Est. completion date: February 28, 2022

Study information

• Verified date: April 2022
• Source: Syneos Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: February 28, 2022
• Est. primary completion date: February 28, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Key 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.

Related Conditions & MeSH terms

• Fatty Liver
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• SRT-015
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.

Other:
• Matching Placebo for SRT-015
Matching Placebo

Locations

Country	Name	City	State
Australia	Nucleus Network Pty Ltd	Victor Harbor	Melbourne

Sponsors (1)

Lead Sponsor	Collaborator
Syneos Health

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the safety and tolerability following of single and multiple oral doses of SRT-015 in healthy subjects	Number of participants with serious and other non-serious adverse events	Up to two weeks
Primary	To evaluate the exposure to SRT-015 following single and multiple oral dose administration in healthy subjects (AUC last)	Area under the serum concentration-time curve from time zero to last measurable concentration (mg*h/L)	Up to two weeks
Primary	3. To evaluate maximum serum concentration of SRT-015 following single and multiple oral dose administration in healthy subjects (Cmax)	Maximum serum concentration (mg/L)	Up to two weeks
Secondary	To compare the exposure to SRT-015 (AUClast) in capsule formulation vs suspension formulation and fed vs fasted state	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)	Up to two weeks
Secondary	To compare maximum serum concentration of SRT-015 (Cmax) in capsule formulation vs suspension formulation and fed v fasted state	Maximum serum concentration (mg/L)	Up to two weeks