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SRT2379

Phase 1

Diabetes Mellitus, Type 2 | Small molecule | Metabolic |GSK plc|Last Updated: Jun 9, 2017

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedACTIVE_CONTROLLEDBiomarker
Total Trials1
Total Enrollment64
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT01018628A Clinical Study to Assess the Safety and Pharmacokinetics of SRT2379 in Normal Healthy Male VolunteersPHASE1 COMPLETED 64Dec 7, 2009Aug 6, 2010Jun 9, 20171 United Kingdom
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Study Endpoints
Primary Endpoints
To determine the safety and tolerability of SRT2379 (25, 75, 250, 500, 1000, 2000, 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers after single and multiple dose administration in the fasted and fed states.
Single Dose Period PK samples will be collected on Day1 at 0h, 15min, 30min, 1, 2, 4, 8, 12 and 24hrs post-dose. Multiple Dose Period PK samples will be collected on Days1-6 at 0h only, and on Day7 at 0h, 15min, 30min, 1, 2, 4, 8, 12 and 24hrs post-dose.
To determine the pharmacokinetic profile of SRT2379 (25, 75, 250, 500, 1000, 2000, 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male volunteers after single and multiple dose administration in the fasted and fed states.
AEs and clinically significant abnormal lab values will be recorded based upon Investigator observation and subject reporting. Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the study.
Secondary Endpoints
To explore the effect of SRT2379 (25, 75, 250, 500, 1000, 2000, and 3000 mg/day [fasted] and 500 mg/day [fed]) on plasma concentrations of Fibroblast Growth Factor 21 (FGF21).
Biomarker samples for plasma FGF-21 analysis will be collected on Day1 (single dose period) and Day7 (multiple dose period) at 0h, 1h, 4h, 8h post-dose and 24hrs post-dose on Days2 (single dose period) and 8 (multiple dose period).
To identify other possible biomarkers suitable for future clinical assessment of oral SIRT1 activators.
Blood samples for analysis of exploratory biomarkers will be collected on Day1 (single dose period) and Day7 (multiple dose period) at 0h, 1h, 4h, 8h post-dose and 24hrs post-dose on Days2 (single dose period) and 8 (multiple dose period).
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Study Design & Arms
AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeBASIC_SCIENCE
Treatment Arms
ArmTypeDescription
Cohort 1 - Dose Level A (25 mg/day)ACTIVE_COMPARATORCohort 1 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 25 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 25 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort.
Cohort 2 - Dose Level B (75 mg/day)ACTIVE_COMPARATORCohort 2 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 75 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 75 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort.
Cohort 3 - Dose Level C (250 mg/day)ACTIVE_COMPARATORCohort 3 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 250 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 250 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort.
Cohort 4 - Dose Level D (500 mg/day)ACTIVE_COMPARATORCohort 4 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 500 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 500 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort.
Cohort 5 - Dose Level E (1000 mg/day)ACTIVE_COMPARATORCohort 5 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 1000 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 1000 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort.
Cohort 6 - Dose Level F (2000 mg/day)ACTIVE_COMPARATORCohort 6 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 2000 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 2000 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort.
Cohort 7 - Dose Level G (3000 mg/day)ACTIVE_COMPARATORCohort 7 will be administered at approximately the same time every dosing day after fasting for 10hrs. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving 3000 mg SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving 3000 mg SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The other cohorts will be dosed sequentially allowing for a comprehensive safety assessment prior to initiation of an escalated dose in a subsequent cohort.
Cohort 8 - Dose Level H (500 mg/day in fed state)ACTIVE_COMPARATORCohort 8 will be administered at approximately the same time every dosing day and 30 minutes following the start of consumption of a standardized high-fat meal. Two subjects will be dosed on Day 1 of the single dose period with one subject receiving SRT2379 and one subject receiving placebo. The remainder of subjects in this cohort will be dosed on Day 2 of the single dose period with five subjects receiving SRT2379 and one subject receiving placebo, assuming that no significant safety issues arise in the two subjects dosed on Day 1. Subjects will remain on a fixed dose of test material for all dosing days in the study. The dose of SRT2379 administered to subjects in the fed state is planned to be 500 mg, however this may be modified upwards or downwards following evaluation of safety and pharmacokinetic data from earlier cohorts. The fed cohort will be the final cohort dosed in the study.
Interventions
NameTypeDescription
SRT2379DRUGSRT2379 will be supplied as hard gelatin capsules, with each containing 25 mg or 250 mg of SRT2379 free base equivalent (31 or 310 mg of SRT2379 monosuccinate) without any additive.
PlaceboDRUGFor placebo product, the SRT2379 drug substance will be replaced by Microcrystalline Cellulose (Avicel® PH 200) to match the SRT2379 investigational product.
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Eligibility Criteria
Age Range18 Years — 55 Years
SexMALE
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * Be male within the age range of 18 to 55 years. * Voluntarily sign an Independent Review Board/Research Ethics Committee (IRB/REC)-approved informed consent form to participate in the study after all relevant aspects of the study have been explained and discussed with the subj...

Countries:United Kingdom
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