A Clinical Study to Assess the Safety and Pharmacokinetics of SRT2379 in Normal Healthy Male Volunteers
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.
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.
Study Design
Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Basic Science
Conditions
Diabetes Mellitus, Type 2
Intervention
SRT2379, Placebo
Location
GSK Investigational Site
Merthyr Tydfill
Glamorgan
United Kingdom
CF48 4DR
Status
Recruiting
Source
GlaxoSmithKline
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT01018628
- Information obtained from ClinicalTrials.gov on July 15, 2010
Published on BioPortfolio: 2014-08-27T03:17:49-0400
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Medical and Biotech [MESH] Definitions
Diabetes Mellitus, Type 2
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.
Prediabetic State
The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).
Diabetes Mellitus, Type 1
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.
Diabetes Mellitus, Lipoatrophic
A type of diabetes mellitus that is characterized by severe INSULIN RESISTANCE and LIPODYSTROPHY. The latter may be generalized, partial, acquired, or congenital (LIPODYSTROPHY, CONGENITAL GENERALIZED).
Diabetic Ketoacidosis
A life-threatening complication of diabetes mellitus, primarily of TYPE 1 DIABETES MELLITUS with severe INSULIN deficiency and extreme HYPERGLYCEMIA. It is characterized by excessive LIPOLYSIS, oxidation of FATTY ACIDS, production of KETONE BODIES, a sweet smell to the breath (KETOSIS;) DEHYDRATION; and depressed consciousness leading to COMA.
