A Clinical Study to Assess the Effect of Food and Gender on the Pharmacokinetics of SRT2104 Administered as an Oral Suspension or Capsule Formulation to Normal Healthy Volunteers

Gender vs. Fed/Fasted State vs. Capsule/Liquid Suspension Formulation Study

The primary objective of this study is to assess the pharmacokinetic profile of a single 500 mg dose of SRT2104 administered as an oral suspension and a capsule formulation to normal healthy male and female volunteers in both the fed and fasted state.

The secondary objective is to assess the safety and tolerance of SRT2104 administered as an oral suspension and as a capsule formulation to healthy male and female volunteers in both the fed and fasted state.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: 0.5g SRT2104

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Glamorgan
    • Merthyr Tydfill, Glamorgan, United Kingdom, CF48 4DR
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Be a healthy male or female within the age range of 18 to 55 years.
• Voluntarily sign a Research Ethics Committee (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 Hematology, Coagulation, Clinical Chemistry and Urinalysis test results that are within normal, allowable limits (if out-of-range, must be considered clinically significant to be exclusionary) and performed within 21 days of receiving first dose of test material.
• Have a BMI (Body Mass Index) between 18.0 and 30.0 kg/m^2.
• Be clear of any history of HIV 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.
• All subjects 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.
• All female subjects must be of non-childbearing 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. (Menopausal status will be confirmed by demonstrating levels of follicle stimulating hormone (FSH) of 20 - 138 mIU/ml and oestradiol < 20 pg/ml at entry. 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.
• Subject agrees to refrain from consumption of grapefruits and/or grapefruit juice from 7 days prior to day -1 of treatment visit 1 through to the end of subject's final study visit.

Exclusion Criteria:

• 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 smokes more than 5 cigarettes a day.
• Subject has a history of alcoholism, 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 (defined as three months from the date of last dose of an investigational medicinal product).
• 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, over-the-counter medication or prescription drug therapy (with the exception of hormone replacement therapy for female subjects) for which 5 times the half-life is longer than 21 days (i.e., the Screening period) prior to enrollment into the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 0.5g SRT2104; Cohort 1 (10 males) & Cohort 2 (10 females) must attend the clinic on 4 separate treatment visits during the study; each treatment visit will be one week apart. At each treatment visit, subjects will receive one of the following 4 treatments: A) 0.5g SRT2104 administered as an oral suspension in the fasted state B) 0.5g SRT2104 administered as an oral suspension following consumption of a standard meal C) 0.5g SRT2104 administered as two 0.25g capsules in the fasted state D) 0.5g SRT2104 administered as two 0.25g capsules following consumption of a standard meal. For treatments A and C, subjects will have fasted for at least 10 hours overnight. Water will be restricted from 1h prior to dosing until 1h post dose. A light lunch will be provided 4h post dose. For treatments B and D, subjects will receive SRT2104 within 30 min following the start of consumption of a standardized non high-fat meal (approximately 650 kcal with approximately 30% of calories derived from fat).

Drug: 0.5g SRT2104; SRT2104 will be supplied in two forms: as 0.5g powder which will be prepared by the pharmacist/designee into a liquid suspension and as two hard gelatin capsules, each containing 0.25g SRT2104. The dosing vehicle for the liquid suspension is 1% (by weight) hypromellose acetate succinate in water, which is used as a suspension aid and a dispersant for the SRT2104. Each formulation of test material will be administered orally, in a single dose to the subjects in the fasted state and following consumption of a standard meal. Neither the investigator nor the subjects enrolled will be blinded to treatment assignment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Characterize and compare the pharmacokinetic profile of a single 500 mg dose of SRT2104 administered as an oral suspension and as a capsule formulation.	PK time points: pre-dose (0 hrs); 0.25, 0.5, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0. 6.0, 8.0, 10, 12, 15, 24, 36, 48, 72 hours post dose.

Secondary Outcome Measures

Outcome Measure	Time Frame
Assess the safety and tolerance of SRT2104.	AEs, concomitant medications (as applicable), vital signs, physical examinations, laboratory parameters, and ECG parameters will be collected for the duration of the study.

Collaborators and Investigators

• Sponsor: Sirtris, a GSK Company
• Collaborators: GlaxoSmithKline

Publications and helpful links

General Publications

• Hoffmann E, Wald J, Lavu S, Roberts J, Beaumont C, Haddad J, Elliott P, Westphal C, Jacobson E. Pharmacokinetics and tolerability of SRT2104, a first-in-class small molecule activator of SIRT1, after single and repeated oral administration in man. Br J Clin Pharmacol. 2013 Jan;75(1):186-96. doi: 10.1111/j.1365-2125.2012.04340.x.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2009
• Primary Completion (Actual): March 27, 2009
• Study Completion (Actual): March 27, 2009

Study Registration Dates

• First Submitted: July 9, 2009
• First Submitted That Met QC Criteria: July 9, 2009
• First Posted (Estimate): July 13, 2009

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 113261

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: 113261
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 113261
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 113261
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 113261
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 113261
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 113261
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 113261
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register