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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Drug :SRT-015 | Active Comparator | Experimental, Single and Multiple Oral escalating dose and Food Effect Cohort |
|
| Matching Placebo for SRT-015 | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SRT-015 | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nucleus Network Pty Ltd | Victor Harbor | Melbourne | 3004 | Australia |
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| ID | Term |
|---|---|
| D065626 | Non-alcoholic Fatty Liver Disease |
| ID | Term |
|---|---|
| D005234 | Fatty Liver |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
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|
| Matching Placebo for SRT-015 | Other | Matching Placebo |
|
| 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 |