A Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Normal Healthy Male Volunteers

NCT00933530 | Completed Phase 1

• 1 other identifier: 113259
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus, Type 2; Healthy Volunteer

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of SRT2104 (0.03, 0.1, 0.25, 0.5, 1.0, 2.0, and 3.0 g/day) when administered as a single dose and when administered once daily for 7 consecutive days.

  Adverse events will be monitored continuously while subjects are on study; safety visits will occur every 7 days for the duration of subject participation.

• Characterize the pharmacokinetic profile of SRT2104 (0.03, 0.1, 0.25, 0.5, 1.0, 2.0, and 3.0 g/day) when administered as a single dose and when administered as once daily for 7 consecutive days.

  Single dose PK timepoints are: predose and 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24hrs postdose. Multiple dose PK timepoints are: Day1 to Day6 predose, Day7 predose, and 15min, 30min, 1h, 2h, 4h, 8h, 12h, 24hrs postdose.

Study Arms (7)

Cohort 1 - Dose Level A (0.03g/day)

EXPERIMENTAL

0.03g SRT2104 dosing will take place at approximately the same time every morning after fasting for at least 10 hours. Subjects will be required to stay overnight at the study center for all dosing days. Six subjects are assigned to this cohort. On Day1 of the single dosing period, one subject will be dosed with 0.03g SRT2014 while one is dosed with placebo on Day1. If no safety issues arise from this dosing, then on Day2, three subjects will be dosed with 0.03g SRT2104 while one is dosed with placebo. Subjects within the cohort will remain on a fixed dose for all dosing days. This cohort of subjects will be dosed sequentially approximately two weeks apart from the single dose period, and return to the clinic approximately one week after their single dose administration to receive 7 consecutive days of daily dosing for the multiple dose period. A comprehensive safety assessment will be conducted one week prior to the initiation of an escalated dose in the subsequent cohort.

Drug: SRT2104; Drug: Placebo

Cohort 2 - Dose Level B (0.1g/day)

EXPERIMENTAL

0.1g SRT2104 dosing will take place at approximately the same time every morning after fasting for at least 10 hours. Subjects will be required to stay overnight at the study center for all dosing days. Six subjects are assigned to this cohort. On Day1 of the single dosing period, one subject will be dosed with 0.1g SRT2014 while one is dosed with placebo on Day1. If no safety issues arise from this dosing, then on Day2, three subjects will be dosed with 0.1g SRT2104 while one is dosed with placebo. Subjects within the cohort will remain on a fixed dose for all dosing days. This cohort of subjects will be dosed sequentially approximately two weeks apart from the single dose period, and return to the clinic approximately one week after their single dose administration to receive 7 consecutive days of daily dosing for the multiple dose period. A comprehensive safety assessment will be conducted one week prior to the initiation of an escalated dose in the subsequent cohort.

Drug: SRT2104; Drug: Placebo

Cohort 3 - Dose Level C (0.25g/day)

EXPERIMENTAL

0.25g SRT2104 dosing will take place at approximately the same time every morning after fasting for at least 10 hours. Subjects will be required to stay overnight at the study center for all dosing days. Six subjects are assigned to this cohort. On Day1 of the single dosing period, one subject will be dosed with 0.25g SRT2014 while one is dosed with placebo on Day1. If no safety issues arise from this dosing, then on Day2, three subjects will be dosed with 0.25g SRT2104 while one is dosed with placebo. Subjects within the cohort will remain on a fixed dose for all dosing days. This cohort of subjects will be dosed sequentially approximately two weeks apart from the single dose period, and return to the clinic approximately one week after their single dose administration to receive 7 consecutive days of daily dosing for the multiple dose period. A comprehensive safety assessment will be conducted one week prior to the initiation of an escalated dose in the subsequent cohort.

Drug: SRT2104; Drug: Placebo

Cohort 4 - Dose Level D (0.5g/day)

EXPERIMENTAL

0.5g SRT2104 dosing will take place at approximately the same time every morning after fasting for at least 10 hours. Subjects will be required to stay overnight at the study center for all dosing days. Six subjects are assigned to this cohort. On Day1 of the single dosing period, one subject will be dosed with 0.5g SRT2014 while one is dosed with placebo on Day1. If no safety issues arise from this dosing, then on Day2, three subjects will be dosed with 0.5g SRT2104 while one is dosed with placebo. Subjects within the cohort will remain on a fixed dose for all dosing days. This cohort of subjects will be dosed sequentially approximately two weeks apart from the single dose period, and return to the clinic approximately one week after their single dose administration to receive 7 consecutive days of daily dosing for the multiple dose period. A comprehensive safety assessment will be conducted one week prior to the initiation of an escalated dose in the subsequent cohort.

Drug: SRT2104; Drug: Placebo

Cohort 5 - Dose Level E (1.0g/day)

EXPERIMENTAL

1.0g SRT2104 dosing will take place at approximately the same time every morning after fasting for at least 10 hours. Subjects will be required to stay overnight at the study center for all dosing days. Six subjects are assigned to this cohort. On Day1 of the single dosing period, one subject will be dosed with 1.0g SRT2014 while one is dosed with placebo on Day1. If no safety issues arise from this dosing, then on Day2, three subjects will be dosed with 1.0g SRT2104 while one is dosed with placebo. Subjects within the cohort will remain on a fixed dose for all dosing days. This cohort of subjects will be dosed sequentially approximately two weeks apart from the single dose period, and return to the clinic approximately one week after their single dose administration to receive 7 consecutive days of daily dosing for the multiple dose period. A comprehensive safety assessment will be conducted one week prior to the initiation of an escalated dose in the subsequent cohort.

Drug: SRT2104; Drug: Placebo

Cohort 6 - Dose Level F (2.0g/day)

EXPERIMENTAL

2.0g SRT2104 dosing will take place at approximately the same time every morning after fasting for at least 10 hours. Subjects will be required to stay overnight at the study center for all dosing days. Six subjects are assigned to this cohort. On Day1 of the single dosing period, one subject will be dosed with 2.0g SRT2014 while one is dosed with placebo on Day1. If no safety issues arise from this dosing, then on Day2, three subjects will be dosed with 2.0g SRT2104 while one is dosed with placebo. Subjects within the cohort will remain on a fixed dose for all dosing days. This cohort of subjects will be dosed sequentially approximately two weeks apart from the single dose period, and return to the clinic approximately one week after their single dose administration to receive 7 consecutive days of daily dosing for the multiple dose period. A comprehensive safety assessment will be conducted one week prior to the initiation of an escalated dose in the subsequent cohort.

Drug: SRT2104; Drug: Placebo

Cohort 7 - Dose Level G (3.0g/day)

EXPERIMENTAL

3.0g SRT2104 dosing will take place at approximately the same time every morning after fasting for at least 10 hours. Subjects will be required to stay overnight at the study center for all dosing days. Six subjects are assigned to this cohort. On Day1 of the single dosing period, one subject will be dosed with 3.0g SRT2014 while one is dosed with placebo on Day1. If no safety issues arise from this dosing, then on Day2, three subjects will be dosed with 3.0g SRT2104 while one is dosed with placebo. Subjects within the cohort will remain on a fixed dose for all dosing days. This cohort of subjects will be dosed sequentially approximately two weeks apart from the single dose period, and return to the clinic approximately one week after their single dose administration to receive 7 consecutive days of daily dosing for the multiple dose period.

Drug: SRT2104; Drug: Placebo

Interventions

SRT2104 DRUG

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.

Also known as: GSK2245840

Cohort 1 - Dose Level A (0.03g/day); Cohort 2 - Dose Level B (0.1g/day); Cohort 3 - Dose Level C (0.25g/day); Cohort 4 - Dose Level D (0.5g/day); Cohort 5 - Dose Level E (1.0g/day); Cohort 6 - Dose Level F (2.0g/day); Cohort 7 - Dose Level G (3.0g/day)

Placebo DRUG

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.

Cohort 1 - Dose Level A (0.03g/day); Cohort 2 - Dose Level B (0.1g/day); Cohort 3 - Dose Level C (0.25g/day); Cohort 4 - Dose Level D (0.5g/day); Cohort 5 - Dose Level E (1.0g/day); Cohort 6 - Dose Level F (2.0g/day); Cohort 7 - Dose Level G (3.0g/day)

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 (IRB/IEC)-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) between 18.0 and 30.0 kg/m2.
• 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.
• Have the ability to communicate with the investigative site staff in a manner sufficient to carry out all protocol procedures as described.
• Subject and their 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.
• Subject agrees to refrain from consumption of grapefruits and/or grapefruit juice from time of study enrollment through end of subject's final study visit.

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 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 (more than two years), and/or is currently drinking more than three drinks per day \[one drink is equal to one unit of alcohol (one glass of wine, half a pint of beer, one measure of a spirit)\].
• 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 products 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.

Sponsors & Collaborators

• Sirtris, a GSK Company: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

GSK Investigational Site

Merthyr Tydfill, Glamorgan, CF48 4DR, United Kingdom

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

SRT2104

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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2009
• First Posted: July 7, 2009
• Study Start: May 1, 2008
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: May 30, 2017

Record last verified: 2017-05

Locations

GB (1)