Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Type 2 Diabetic Human Subjects

NCT ID: NCT00937326

Last Updated: 2018-07-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 227 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-19
• Study Completion Date: 2010-09-18

Brief Summary

The primary purpose of this study is to determine the safety and tolerability of SRT2104 (0.25, 0.5, 1.0, and 2.0 g/day) in type 2 diabetic subjects when administered once daily for 28 consecutive days, and to characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in type 2 diabetic subjects.

The secondary purpose of this study is to determine the effect of SRT2104 (0.25, 0.5, 1.0, and 2.0 g/day) when administered once daily for 28 consecutive days on fasting blood glucose and insulin and post-prandial blood glucose and insulin in type 2 diabetic subjects.

Detailed Description

Study Objectives

Primary:

1. To determine the safety and tolerability of SRT2104 (0.25, 0.5, 1.0, and 2.0 g/day) in type 2 diabetic subjects when administered once daily for 28 consecutive days.

2. To characterize the pharmacokinetic profile of SRT2104 (0.25, 0.5, 1.0, and 2.0 g/day) after a single dose and multiple administrations in type 2 diabetic subjects.

Secondary:

1. To determine the effect of SRT2104 (0.25, 0.5, 1.0, and 2.0 g/day) when administered once daily for 28 consecutive days on fasting blood glucose and insulin and post-prandial blood glucose and insulin in type 2 diabetic subjects.

Study Design:

Prospective, multi-center, clinical study of SRT2104 administered orally once daily for 28 consecutive days; randomized, placebo-controlled, double-blind, multiple-dose, inpatient/outpatient study to assess the safety and pharmacokinetics (PK) of SRT2104 in type 2 diabetic male and female subjects on an existing, stable, background metformin therapy. Approximately 225 subjects aged 30-70, who fulfill the inclusion/exclusion criteria, will be enrolled in this study to ensure completion of forty (40) evaluable subjects within each of five dosing groups. Subjects will be evenly randomized to receive SRT2104 at one of five doses, placebo (A), 0.25 g/day (B), 0.5 g/day (C), 1.0 g/day (D), or 2.0 g/day (E), once a day for 28 consecutive days, approximately 15 minutes following consumption of a standardized meal. Subjects will remain on a fixed dose of test material for all dosing days in the study.

Subjects will sign the informed consent form at the Screening Visit, and will undergo screening assessments over a 2-day period to verify eligibility for the study. If eligible and willing to participate, subjects will return to the clinic within 21 days of the Screening Visit to participate in the dosing phase of the study. Subjects will be randomized to receive SRT2104 or placebo, and will be required to stay overnight at the study center on Day -1 and Day 27 to gather required PK samples and to assess safety on Day 1 and Day 28 respectively. In addition, subjects will be asked to return to the study center on Days 2 and 29; for three interim weekly safety assessments (on Days 8, 15, 22); and for an End of Study safety assessment 7 days after they complete the 28-day dosing period. A follow-up safety call will be made to each subject 30 days following their final dose of SRT2104 or placebo.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

The Placebo treatment group will be administered eight placebo capsules per day.

Placebo will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, approximately 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.

Arm1 - 0.25g

The 0.25g SRT2104 treatment group will be administered one SRT2104 capsules with 7 placebo capsules, for a total of 8 capsules per day.

0.25g SRT2104 will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.

Group Type: ACTIVE_COMPARATOR

SRT2104

Intervention Type: DRUG

SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.

Placebo

Intervention Type: DRUG

Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.

Arm2 - 0.5g

The 0.5g SRT2104 treatment group will be administered two SRT2104 capsules with 6 placebo capsules, for a total of 8 capsules per day.

0.5g SRT2104 will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.

Group Type: ACTIVE_COMPARATOR

SRT2104

Intervention Type: DRUG

SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.

Placebo

Intervention Type: DRUG

Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.

Arm3 - 1g

The 1g SRT2104 treatment group will be administered four SRT2104 capsules with four placebo capsules, for a total of 8 capsules per day.

1g SRT2104 will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.

Group Type: ACTIVE_COMPARATOR

SRT2104

Intervention Type: DRUG

SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.

Placebo

Intervention Type: DRUG

Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.

Arm4 - 2g

The 2g SRT2104 treatment group will be administered eight SRT2104 capsules per day.

2g SRT2104 will be administered orally once daily for twenty-eight consecutive days. Dosing will take place at approximately the same time every morning, 15 minutes following consumption of a standardized meal and should be administered with approximately 1 to 2 glasses of water.

Group Type: ACTIVE_COMPARATOR

SRT2104

Intervention Type: DRUG

SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.

Interventions

SRT2104

SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.

Intervention Type: DRUG

Placebo

Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Subjects of any race and gender within the age range of 30 to 70 years.

2. All female subjects must be of non-child-bearing potential. For the purposes of this study, this is defined as the subject being amenorrheic for at least 12 consecutive months, or at least 6 weeks post-surgical bilateral oophorectomy with or without hysterectomy, or women who underwent tubal ligation. Menopausal status will be confirmed by demonstrating levels of follicle stimulating hormone (FSH) 40 - 138 mIU/ml and oestradiol < 20 pg/ml at entry, unless this information is available in the subject's medical record. In the event a subject's menopause status has been clearly established (for example, the subject indicates she has been amenorrheic for 10 years), but FSH and/or oestradiol levels are not consistent with a post-menopausal condition, determination of subject eligibility will be at the discretion of the principal investigator following consultation with the sponsor and medical monitor

3. All male subjects must agree with their partners to use double-barrier birth control or abstinence while participating in the study and for 12 weeks following the last dose of study drug.

4. Willingness to provide written informed consent to participate in the study

5. HbA1c ≥ 7.5 and ≤ 10.5

6. Fasting glucose ≥ 160 and ≤ 240 mg/dL

7. Body Mass Index (BMI) ≥ 25.0 kg/m^2 and ≤ 40.0 kg/m^2

8. On stable metformin medication for at least 3 months (≥ 1.0 g/day) prior to Screening

9. No prior history of HIV 1 or 2

10. Absence of disease markers for hepatitis B & C virus

11. Absence of significant disease or clinically significant abnormal laboratory values on the laboratory evaluations, medical history or physical examination during the screening; normal end organ function

12. Have a normal 12-lead ECG or one with abnormality considered to be clinically insignificant

13. Have a normal chest X-ray (P. A. View) or one with abnormality considered to be clinically insignificant

14. Comprehension of the nature and purpose of the study and compliance with the requirement of the entire protocol

Exclusion Criteria

1. Any major illness in the past three months or any significant ongoing chronic medical illness not related to diabetes

2. Renal or liver impairment, defined as serum creatinine level of ≥ 1.4 mg/dL for females and ≥ 1.5 mg/dL for males, and greater than two times the upper limit of normal for liver enzymes, respectively.

3. History of or current gastro-intestinal diseases influencing drug absorption, except for appendectomy

4. History, within 3 years, of drug abuse (including Benzodiazepines, opioids, amphetamine, cocaine, and THC)

5. History of alcoholism (more than two years), moderate drinkers (more than three drinks per day) or having consumed alcohol within 48 hrs prior to dosing [one drink is equal to one unit of alcohol (one glass wine, half pint beer, one measure of spirit)]

6. Participation in any clinical trial within the past three months

7. History of difficulty in donating blood or accessibility of veins in left or right arm

8. Donation of blood (one unit or 350 ml) within three months prior to receiving the first dose of test material

9. Use of any prescription drug therapy, with exception of any prescription medication administered at a stable dose for at least 6 weeks prior to Screening, provided the medication is not contraindicated by the metformin label

10. Use of any alternate anti-diabetic therapy, except metformin, within three months of enrollment

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Sirtris, a GSK Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Byala, , Bulgaria

GSK Investigational Site

Dimitrovgrad, , Bulgaria

GSK Investigational Site

Haskovo, , Bulgaria

GSK Investigational Site

Pleven, , Bulgaria

GSK Investigational Site

Plovdiv, , Bulgaria

GSK Investigational Site

Plovdiv, , Bulgaria

GSK Investigational Site

Rousse, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Balantonfured, , Hungary

GSK Investigational Site

Eger, , Hungary

GSK Investigational Site

Gyula, , Hungary

GSK Investigational Site

Kecskemét, , Hungary

GSK Investigational Site

Sopron, , Hungary

GSK Investigational Site

Szekszárd, , Hungary

GSK Investigational Site

Zalaegerszeg, , Hungary

GSK Investigational Site

Cieszyn, , Poland

GSK Investigational Site

Lubin, , Poland

GSK Investigational Site

Lubin, , Poland

GSK Investigational Site

Puławy, , Poland

GSK Investigational Site

Radzymin, , Poland

GSK Investigational Site

Ruda Śląska, , Poland

GSK Investigational Site

Słupsk, , Poland

GSK Investigational Site

Tychy, , Poland

GSK Investigational Site

Warsaw, , Poland

GSK Investigational Site

Bacau, , Romania

GSK Investigational Site

Brăila, , Romania

GSK Investigational Site

Buzău, , Romania

GSK Investigational Site

Constanța, , Romania

GSK Investigational Site

Oradea, , Romania

GSK Investigational Site

Ploieşti, , Romania

GSK Investigational Site

Timișoara, , Romania

GSK Investigational Site

Barnaul, , Russia

GSK Investigational Site

Kemerovo, , Russia

GSK Investigational Site

Kemerovo, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Rostov-on-Don, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Tyumen, , Russia

GSK Investigational Site

Ufa, , Russia

GSK Investigational Site

Yaroslavl, , Russia

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Mykolaiv, , Ukraine

GSK Investigational Site

Simferopol, , Ukraine

GSK Investigational Site

Ternopil, , Ukraine

GSK Investigational Site

Vinnitsa, , Ukraine

GSK Investigational Site

Zaporizhzhya, , Ukraine

GSK Investigational Site

Zaporizhzhya, , Ukraine

GSK Investigational Site

Birmingham, , United Kingdom

GSK Investigational Site

London, , United Kingdom

GSK Investigational Site

Newport, , United Kingdom

Countries

Bulgaria; Estonia; Hungary; Poland; Romania; Russia; Ukraine; United Kingdom

Study Documents

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

113160

Identifier Type: -

Identifier Source: org_study_id