A Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Normal Healthy Male Volunteers
Condition: Diabetes Mellitus, Type 2; Healthy Volunteer
MeSH terms: Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the safety and tolerability of SRT2104 (0.03, 0.1,
      0.25, 0.5, 1.0, 2.0, and 3.0 g/day) in healthy male volunteers when administered after a
      single dose and once daily for 7 consecutive days.

      The purpose is also to characterize the pharmacokinetic profile of SRT2104 (0.03, 0.1, 0.25,
      0.5, 1.0, 2.0, and 3.0 g/day) after a single dose and multiple administrations in healthy
      male volunteers.
    

Detailed description: 
      Prospective, single center, clinical study of SRT2104 administered orally. Randomized,
      placebo-controlled, single-blind, multiple-dose, dose-escalation inpatient/outpatient study
      to assess the safety and pharmacokinetics (PK) of SRT2104 in healthy male volunteers.
      Forty-two (42) subjects aged 18-55, who fulfill the inclusion/exclusion criteria, will be
      enrolled in this study. Seven cohorts of six subjects each will be examined. Subjects within
      each cohort will be randomized 4:2 to receive SRT2104 at one of seven escalating doses (A, B,
      C, D, E, F, or G), likely to be 0.03, 0.1, 0.25, 0.5, 1.0, 2.0, or 3.0 g/day or placebo. 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 three 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 two weeks apart for the
      single dose period, and return to the clinic approximately one week 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, one
      week apart, allowing for a comprehensive safety assessment prior to initiation of an
      escalated dose in a subsequent cohort. In the event of suspected drug related toxicity, as
      determined by the principal investigator, sponsor, and an independent medical monitor, at a
      dose of 0.03 g/day, all subjects in the 0.03 g/day cohort will discontinue dosing, and the
      subsequent cohort will receive 0.01 g/day for seven consecutive days. Safety and PK-related
      data will be reviewed for the 0.01 g/day dose level, and no subsequent cohorts will be
      enrolled into the study.

      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 SRT2104 or placebo (test material). Subjects
      will be required to stay overnight at the study center for two nights during the single dose
      period of the study and subsequently, for the duration of the seven-day multiple dose period
      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 1 week after they complete 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): SRT2104; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): SRT2104 (0.03, 0.1, 0.25, 0.5, 1.0, 2.0, or 3.0 g/day) will be supplied as a powder which will be prepared by the Pharmacist/designee into a liquid suspension. The dosing vehicle is 1% (by weight) hypromellose acetate succinate in water, which is used as a suspension aid and a dispersant for the SRT2104. Test material will be administered orally, in a single dose and subsequently, once daily for seven consecutive days. A trained staff member will prepare individual solutions of test material that the subject will drink once daily in the clinic following a 10-hour (minimum) fast.; Placebo (at the matched dosage as SRT2104) will be supplied as a powder which will be prepared by the Pharmacist/designee into a liquid suspension. Placebo will consist of titanium dioxide USP and prepared for oral administration identically to the SRT2104 investigational product. Test material will be administered orally, in a single dose and subsequently, once daily for seven consecutive days. The subjects enrolled will be blinded to treatment assignment. A trained staff member will prepare individual solutions of test material that the subject will drink once daily in the clinic following a 10-hour (minimum) fast.
Other intervention name(s): GSK2245840
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science