A Clinical Study to Assess the Safety and Pharmacokinetics of SRT2379 in Normal Healthy Male Volunteers

NCT01018628 | Completed Phase 1

• 1 other identifier: 114011
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• 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).

Study Arms (8)

Cohort 1 - Dose Level A (25 mg/day)

ACTIVE COMPARATOR

Cohort 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.

Drug: SRT2379; Drug: Placebo

Cohort 2 - Dose Level B (75 mg/day)

ACTIVE COMPARATOR

Cohort 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.

Drug: SRT2379; Drug: Placebo

Cohort 3 - Dose Level C (250 mg/day)

ACTIVE COMPARATOR

Cohort 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.

Drug: SRT2379; Drug: Placebo

Cohort 4 - Dose Level D (500 mg/day)

ACTIVE COMPARATOR

Cohort 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.

Drug: SRT2379; Drug: Placebo

Cohort 5 - Dose Level E (1000 mg/day)

ACTIVE COMPARATOR

Cohort 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.

Drug: SRT2379; Drug: Placebo

Cohort 6 - Dose Level F (2000 mg/day)

ACTIVE COMPARATOR

Cohort 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.

Drug: SRT2379; Drug: Placebo

Cohort 7 - Dose Level G (3000 mg/day)

ACTIVE COMPARATOR

Cohort 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.

Drug: SRT2379; Drug: Placebo

Cohort 8 - Dose Level H (500 mg/day in fed state)

ACTIVE COMPARATOR

Cohort 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.

Drug: SRT2379; Drug: Placebo

Interventions

SRT2379 DRUG

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.

Cohort 1 - Dose Level A (25 mg/day); Cohort 2 - Dose Level B (75 mg/day); Cohort 3 - Dose Level C (250 mg/day); Cohort 4 - Dose Level D (500 mg/day); Cohort 5 - Dose Level E (1000 mg/day); Cohort 6 - Dose Level F (2000 mg/day); Cohort 7 - Dose Level G (3000 mg/day); Cohort 8 - Dose Level H (500 mg/day in fed state)

Placebo DRUG

For placebo product, the SRT2379 drug substance will be replaced by Microcrystalline Cellulose (Avicel® PH 200) to match the SRT2379 investigational product.

Cohort 1 - Dose Level A (25 mg/day); Cohort 2 - Dose Level B (75 mg/day); Cohort 3 - Dose Level C (250 mg/day); Cohort 4 - Dose Level D (500 mg/day); Cohort 5 - Dose Level E (1000 mg/day); Cohort 6 - Dose Level F (2000 mg/day); Cohort 7 - Dose Level G (3000 mg/day); Cohort 8 - Dose Level H (500 mg/day in fed state)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 subject.
• Have a BMI (Body Mass Index) ≥18.0 and ≤30.0 kg/m\^2.
• Be clear of any history of HIV 1 and 2 and hepatitis B and C.
• Have no significant disease or clinically significant abnormal laboratory value as deemed by the Investigator on the laboratory evaluations, medical history, or physical exam.
• Have a normal 12-lead ECG or an ECG with abnormality considered to be clinically insignificant. Specifically, the QTcB must be ≤ 450 msec, and no evidence of bundle branch block must be present.
• Have the ability to communicate with the investigative site staff in a manner sufficient to carry out all protocol procedures as described.
• Subject and his partner must agree to use an acceptable double barrier method for birth control from the Screening visit through 3 months after the last dose of test material.

You may not qualify if:

• Subject has had a major illness in the past three months or any significant ongoing chronic medical illness that the Investigator would deem unfavorable for enrollment.
• Subject has renal or liver impairment.
• Subject has clinically significant findings on Screening 24 hour 12-lead Holter.
• Subject has a history of gastro-intestinal surgery or has a current gastrointestinal disease which may influence drug absorption.
• Subject has a history, within 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, and THC) or a positive drug result at Screening.
• Subject has a history of smoking, within 3 months, or is currently a smoker.
• Subject has a history of alcoholism, and/or is currently drinking more than three drinks per day on a regular basis \[one drink is equal to one unit of alcohol (one glass of wine, half a pint of beer, one measure of a spirit)\].
• Subject has participated in a clinical trial within the past three months.
• Subject has a history of difficulty in donating blood or accessibility of veins in left or right arm.
• Subject has donated blood (one unit or 350 mL) within three months prior to receiving test material.
• Subject is taking herbal and dietary supplements or prescription drug therapy for which 5 times the half-life is longer than 21 days (i.e., the Screening period) prior to enrollment into the study. Please note: subjects must refrain from taking herbal or dietary supplements for the duration of the study.
• Unwillingness or inability to follow the procedures outlined in the protocol.
• Subject is mentally or legally incapacitated.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Merthyr Tydfill, Glamorgan, CF48 4DR, United Kingdom

Location

Related Publications (1)

• GSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing a results summary with a conclusion.

  BACKGROUND

Related Links

• Results for study 114011 can be found on the GSK Clinical Study Register.
• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2009
• First Posted: November 23, 2009
• Study Start: December 7, 2009
• Primary Completion: August 6, 2010
• Study Completion: August 6, 2010
• Last Updated: June 9, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)