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

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00937326
First received: July 9, 2009
Last updated: December 1, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: SRT2104
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Phase II, Randomized, Placebo-Controlled, Double-Blind, Multiple-Dose Clinical Study to Assess the Safety and Pharmacokinetics of SRT2104 in Type 2 Diabetic Human Subjects

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Incidence of AEs and clinically significant abnormal laboratory values reported. [ Time Frame: From administration of first dose to 30 days following last dose. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pharmacokinetic analyses, change in fasting and in post-prandial glucose and insulin levels, and change in HbA1c. [ Time Frame: Treatment phase of 28 days. ] [ Designated as safety issue: No ]

Enrollment: 225
Study Start Date: August 2009
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: 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.

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

Drug: SRT2104
SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.
Drug: Placebo
Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
Active Comparator: 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.

Drug: SRT2104
SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.
Drug: Placebo
Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
Active Comparator: 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.

Drug: SRT2104
SRT2104 will be supplied as hard gelatin capsules, with each containing 250 mg.
Drug: Placebo
Placebo will be supplied as hard gelatin capsules, with each containing an appropriate amount of placebo.
Active Comparator: 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.

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

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.

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00937326

  Show 61 Study Locations
Sponsors and Collaborators
Sirtris, a GSK Company
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT00937326     History of Changes
Other Study ID Numbers: 113160
Study First Received: July 9, 2009
Last Updated: December 1, 2011
Health Authority: Estonia: State Agency of Medicines
Ukraine: Central Ethics Committee;
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Bulgaria: The Bulgarian Drug Agency
Romania: Agentia Nationala a Medicamentului
Russia: Russian Ministry of Health
Hungary: Országos Gyógyszerészeti Intézet
Poland: URZ.D REJESTRACJI PRODUKTÓW LECZNICZYCH, WYROBÓW MEDYCZNYCH I PRODUKTÓW BIOBÓJCZYCH,CEBK

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 23, 2014