A Study to Assess the Relative Bioavailability of New Oral Formulations of SRT2104 in Healthy Male Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline ( Sirtris, a GSK Company )
ClinicalTrials.gov Identifier:
NCT01702493
First received: October 4, 2012
Last updated: April 5, 2013
Last verified: April 2013
  Purpose

This is an open-label, randomized, controlled, single center study to assess the safety, variability in exposure, and relative bioavailability of new oral formulations of SRT2104. This is a two part study and each part consists of screening (within 21 days of the first scheduled dose of SRT2104), treatment period and follow-up visit (approximately 6 days after the last dose). Part 1: Subjects will receive all four fomulations of SRT2104 and their order of their doses will be randomized. Each subject will receive one formulation as a 500 milligram (mg) dose (in the form of two 250 mg capsules or tablets) in each session given in the fasted state. Each dose will be separated by at least 6 days. Pharmacokinetic (PK) sampling will be done pre and post each scheduled dosing session. After all 4 dosing sessions, the safety and PK data will be reviewed to determine which, if any, formulation(s) will be carried forward into Part 2. The total duration will be approximately 7 weeks. Part 2: Is further divided into Part 2A, 2B and 2C of the study and are optional. After the completion of Part 1, the sponsor will decide whether to proceed with any or all of Part 2, and whether the selected formulation(s) is to be administered in the fed or fasted state for Parts 2B and 2C. For all the sub parts of Part 2 the pre and post-dose PK samples will be obtained. Part 2A: A single-dose of the selected formulation(s) from Part 1 will be administered after a standard meal to assess the effect of food on the bioavailability of SRT2104 at the 500 mg dose. The total duration will be approximately 4 weeks. Part 2B: A single alternative dose (other than 500 mg, but not to exceed 2000 mg) of the selected formulation(s) from Part 1 will be administered to assess the safety and PK profile of this dose level. The total duration will be approximately 4 weeks. Part 2C: The selected formulation(s) from Part 1 will be administered at the 500 mg dose once daily for 7 consecutive days, to assess the safety and tolerability and characterize the PK profile of repeat dosing. The total duration will be approximately 5 weeks.


Condition Intervention Phase
Psoriasis
Drug: Cap SRT2104
Drug: Tab SRT2104 slow release
Drug: Tab SRT2104 intermediate release
Drug: Tab SRT2104 fast release
Drug: Selected formulations of SRT2104 from Part 1
Drug: Selected formulations of SRT2104 from Part 1 single alternative dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Bio-availability Study
Intervention Model: Crossover Assignment
Masking: Open Label
Official Title: A Phase 1, Open-Label, Randomized, Controlled, Four-Period Crossover Study to Assess the Relative Bioavailability of New Oral Formulations of SRT2104 in Healthy Male Volunteers

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Measure of variability in exposure-CVw [ Time Frame: Part 1: Days 1, 8, 15 and 22; Parts 2A and 2B: Day 1; Part 2C: Days 1 to 7. Pre dose and post-dose at 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after each scheduled dosing session. ] [ Designated as safety issue: No ]
    The variability in exposure of SRT2104 will be assessed by calculating the within subject coefficient of variation (CVw).

  • Measure of relative bioavailability-AUC [ Time Frame: Part 1: Days 1, 8, 15 and 22; Parts 2A and 2B: Day 1; Part 2C: Days 1 to 7. Pre dose and post-dose at 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after each scheduled dosing session. ] [ Designated as safety issue: No ]
    Relative bioavailability of SRT2104 will be assessed by evaluating area under the curve (AUC).

  • Measure of relative bioavailability-Cmax [ Time Frame: Part 1: Days 1, 8, 15 and 22; Parts 2A and 2B: Day 1; Part 2C: Days 1 to 7. Pre dose and post-dose at 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after each scheduled dosing session. ] [ Designated as safety issue: No ]
    Relative bioavailability of SRT2104 will be assessed by measuring maximum observed plasma concentration (Cmax).

  • Measure of relative bioavailability-Tmax [ Time Frame: Part 1: Days 1, 8, 15 and 22; Parts 2A and 2B: Day 1; Part 2C: Days 1 to 7. Pre dose and post-dose at 15 minutes, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours after each scheduled dosing session. ] [ Designated as safety issue: No ]
    Relative bioavailability of SRT2104 will be assessed by measuring the time to reach maximum observed plasma concentration (Tmax).

  • Safety of SRT2104 as assessed by number of subjects with adverse events (AE)s [ Time Frame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. ] [ Designated as safety issue: No ]
    Safety parameter will include recording number of AEs, throughout the study.

  • Safety of SRT2104 as assessed by intensity of AEs [ Time Frame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. ] [ Designated as safety issue: No ]
    Safety parameter will include recording of intensity of AEs, throughout the study.

  • Safety of SRT2104 as assessed by type of AEs [ Time Frame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. ] [ Designated as safety issue: No ]
    Safety parameter will include recording of type of AEs, throughout the study.

  • Safety of SRT2104 as assessed by change from Baseline in heart rate [ Time Frame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. ] [ Designated as safety issue: No ]
    Safety will be assessed by recording heart rate at Baseline and at end of the study.

  • Safety of SRT2104 as assessed by change from Baseline in blood pressure [ Time Frame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. ] [ Designated as safety issue: No ]
    Safety will be assessed by recording blood pressure at Baseline and at end of the study.

  • Safety of SRT2104 as assessed by change from Baseline in temperature [ Time Frame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. ] [ Designated as safety issue: No ]
    Safety will be assessed by recording temperature at Baseline and at end of the study.

  • Safety of SRT2104 as assessed by change from Baseline in ECG readings [ Time Frame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. ] [ Designated as safety issue: No ]
    Safety will be assessed by recording the electrocardiogram (ECG) readings at Baseline and at end of the study.

  • Safety of SRT2104 as assessed by change from Baseline in clinical laboratory parameters [ Time Frame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks. ] [ Designated as safety issue: No ]
    Clinical laboratory parameters will include hematology, clinical chemistry and electrolytes, serology, coagulation and urinalysis. Safety will be assessed by evaluating the clinical laboratory parameter readings at Baseline and at end of the study.


Enrollment: 16
Study Start Date: October 2012
Study Completion Date: December 2012
Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Part 1: Cap SRT2104
500 mg SRT2104 (in the form of two, 250 mg capsules) will be administered as a single oral dose in the fasting state
Drug: Cap SRT2104
Micronized free base in a 250 mg SRT2104 (active equivalents) capsule
Experimental: Part 1: Tab SRT2104 (slow release)
500 mg SRT2104 (in the form of two, 250 mg slow release tablets) will be administered as a single oral dose in the fasting state.
Drug: Tab SRT2104 slow release
New 250 mg SRT2104 mesylate salt slow release tablet
Experimental: Part 1: Tab SRT2104 (intermediate release)
500 mg SRT2104 (in the form of two, 250 mg intermediate release tablets) will be administered as a single oral dose in the fasting state.
Drug: Tab SRT2104 intermediate release
New 250 mg SRT2104 mesylate salt intermediate release tablet
Experimental: Part 1: Tab SRT2104 (fast release)
500 mg SRT2104 (in the form of two, 250 mg fast release tablets) will be administered as a single oral dose in the fasting state.
Drug: Tab SRT2104 fast release
New 250 mg SRT2104 mesylate salt fast release tablet
Experimental: Part 2A: SRT2104 500 mg single-dose
500 mg SRT2104 (formulation selected from Part 1) will be administered as a single oral dose in the fed state.
Drug: Selected formulations of SRT2104 from Part 1
SRT2104 500 mg of selected formulation(s) from Part 1 in single-dose or daily for 7 days
Experimental: Part 2B: SRT2104 single alternative dose
An alternative dose (other than 500 mg, but not to exceed 2000 mg) of SRT2104 (formulation selected from Part 1) will be administered as a single oral dose.
Drug: Selected formulations of SRT2104 from Part 1 single alternative dose
SRT2104 single alternative dose (other than 500 mg, but not to exceed 2000 mg) of selected formulation(s) from Part 1
Experimental: Part 2C: SRT2104 500 mg daily for 7 days
500 mg SRT2104 (formulation selected from Part 1) will be administered daily for 7 days.
Drug: Selected formulations of SRT2104 from Part 1
SRT2104 500 mg of selected formulation(s) from Part 1 in single-dose or daily for 7 days

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy as determined by a responsible and experienced physician.
  • Males between 18 and 65 years of age inclusive, at the time of signing the informed consent.
  • Body weight >=50 kilogram (kg) (110 lbs) and body mass index (BMI) >=18.
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

Exclusion Criteria:

  • Past or present disease that is judged by the investigator to have the potential to interfere with the study procedures or compromise the subject's safety.
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones), or aspartate aminotranferase (AST), alanine aminotranferase (ALT), alkaline phosphatase and bilirubin >1.5 x upper limit of normal (ULN).
  • Abnormalities on the Screening or Day -1: electrocardiogram (ECG) that, in the opinion of the investigator, will compromise subject safety in the study or QT corrected using Fridericia's formula (QTcF) > 450 milliseconds (msec).
  • A history of Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV), or positive serology at Screening.
  • History of regular alcohol consumption within 6 months of the Screening (Screening visit) and a positive pre-study drug/alcohol screen.
  • Participation in a clinical trial and treatment with an investigational product within 3 months prior to Screening visit.
  • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that contraindicates their participation.
  • History of sensitivity to heparin or heparin-induced thrombocytopenia.
  • Where participation in the study would result in the inability to donate blood or blood products in excess of 500 milliliter (mL) within a 56 day period.
  • Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
  • Consumption of red wine, seville oranges, grapefruit or grapefruit juice [and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices] from 7 days prior to the first dose of study medication.
  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: NCT01702493

Locations
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21225
Sponsors and Collaborators
Sirtris, a GSK Company
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline ( Sirtris, a GSK Company )
ClinicalTrials.gov Identifier: NCT01702493     History of Changes
Other Study ID Numbers: 117041
Study First Received: October 4, 2012
Last Updated: April 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
SRT2104
Modified Release
Bioavailability
Crossover

ClinicalTrials.gov processed this record on September 18, 2014