A Clinical Study to Assess the Safety and Pharmacokinetics of SRT2379 in Normal Healthy Male Volunteers
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

Summary: 
      The main purpose of this study is to assess the safety and pharmacokinetics of SRT2379 (25,
      75, 250, 500, 1000, 2000, and 3000 mg/day [fasted] and 500 mg/day [fed]) in healthy male
      volunteers.

      The purpose is also to explore the effect of SRT2379 on plasma concentrations of Fibroblast
      Growth Factor 21 (FGF21) and to identify other possible biomarkers suitable for future
      clinical assessment of oral SIRT1 activators.
    

Detailed description: 
      Prospective, single center, clinical study of SRT2379 administered orally. Randomized,
      placebo-controlled, single-blind, multiple-dose, dose-escalation inpatient/outpatient study
      to assess the safety and pharmacokinetics (PK) of SRT2379 in healthy male volunteers.
      Approximately sixty-four (64) subjects aged 18-55, who fulfill the inclusion/exclusion
      criteria, will be enrolled in this study. Eight cohorts of eight subjects each will be
      examined. Subjects within each cohort will be randomized 6:2 to receive SRT2379 at one of
      seven escalating doses (A, B, C, D, E, F or G), likely to be 25, 75, 250, 500, 1000, 2000,
      and 3000 mg/day or placebo. All cohorts will be administered SRT2379 in the fasted state,
      with the exception of one cohort that will receive one of the stated doses of SRT2379 in the
      fed state (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.). Two subjects will be dosed on Day 1 of the single dose period with one subject
      receiving active treatment and one subject receiving placebo. The remainder of subjects
      within each cohort will be dosed on Day 2 of the single dose period with five subjects
      receiving active treatment and one subject receiving placebo, assuming that no 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.

      Each cohort of subjects will be dosed sequentially approximately three weeks apart for the
      single dose period, and return to the study unit approximately two weeks after their single
      dose administration to receive 7 consecutive days of dosing for the multiple-dose period.
      Each cohort of subjects in the multiple-dose period will be dosed sequentially,
      approximately, two weeks apart (from multiple dose period Day 7 of preceding cohort to
      multiple dose period Day 1 dose of the subsequent cohort), allowing for a comprehensive
      safety assessment prior to initiation of an escalated dose in a subsequent cohort.

      Subjects will sign the informed consent form at the Screening Visit. If eligible and willing
      to participate, subjects will enter into the study. Subjects will have fasted for at least 10
      hours overnight and be randomized to receive SRT2379 or placebo (test material). The subject
      cohort assigned to the fed dose will consume a standardized meal before receiving test
      material; all other subjects will receive test material in a fasted state. Subjects will be
      required to stay overnight at the study unit for two nights during the single dose period of
      the study and subsequently, for the duration of the seven-day multiple-dose period (8
      consecutive overnight stays) to assess safety and to gather required PK samples. Subjects
      will be asked to return to the study center for an End of Study safety assessment
      approximately 1 week after the last administration of study drug during the multiple-dose
      period.

      Dose escalation will be dependent on safety parameters (physical examination findings, vital
      signs, ECG studies, adverse events and laboratory values) and PK data.
    

Intervention name(s): SRT2379; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): SRT2379 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.; For placebo product, the SRT2379 drug substance will be replaced by Microcrystalline Cellulose (Avicel® PH 200) to match the SRT2379 investigational product.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Basic Science