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

Primary Purpose

Psoriasis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cap SRT2104
Tab SRT2104 slow release
Tab SRT2104 intermediate release
Tab SRT2104 fast release
Selected formulations of SRT2104 from Part 1
Selected formulations of SRT2104 from Part 1 single alternative dose
Sponsored by
Sirtris, a GSK Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Psoriasis focused on measuring SRT2104, Modified Release, Bioavailability, Crossover

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

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.

Sites / Locations

  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Active Comparator

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Part 1: Cap SRT2104

Part 1: Tab SRT2104 (slow release)

Part 1: Tab SRT2104 (intermediate release)

Part 1: Tab SRT2104 (fast release)

Part 2A: SRT2104 500 mg single-dose

Part 2B: SRT2104 single alternative dose

Part 2C: SRT2104 500 mg daily for 7 days

Arm Description

500 mg SRT2104 (in the form of two, 250 mg capsules) will be administered as a single oral dose in the fasting state

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.

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.

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.

500 mg SRT2104 (formulation selected from Part 1) will be administered as a single oral dose in the fed state.

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.

500 mg SRT2104 (formulation selected from Part 1) will be administered daily for 7 days.

Outcomes

Primary Outcome Measures

Measure of variability in exposure-CVw
The variability in exposure of SRT2104 will be assessed by calculating the within subject coefficient of variation (CVw).
Measure of relative bioavailability-AUC
Relative bioavailability of SRT2104 will be assessed by evaluating area under the curve (AUC).
Measure of relative bioavailability-Cmax
Relative bioavailability of SRT2104 will be assessed by measuring maximum observed plasma concentration (Cmax).
Measure of relative bioavailability-Tmax
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
Safety parameter will include recording number of AEs, throughout the study.
Safety of SRT2104 as assessed by intensity of AEs
Safety parameter will include recording of intensity of AEs, throughout the study.
Safety of SRT2104 as assessed by type of AEs
Safety parameter will include recording of type of AEs, throughout the study.
Safety of SRT2104 as assessed by change from Baseline in heart rate
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
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
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
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
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.

Secondary Outcome Measures

Full Information

First Posted
October 4, 2012
Last Updated
June 9, 2017
Sponsor
Sirtris, a GSK Company
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1. Study Identification

Unique Protocol Identification Number
NCT01702493
Brief Title
A Study to Assess the Relative Bioavailability of New Oral Formulations of SRT2104 in Healthy Male Volunteers
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
October 30, 2012 (Actual)
Primary Completion Date
December 5, 2012 (Actual)
Study Completion Date
December 5, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sirtris, a GSK Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis
Keywords
SRT2104, Modified Release, Bioavailability, Crossover

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1: Cap SRT2104
Arm Type
Active Comparator
Arm Description
500 mg SRT2104 (in the form of two, 250 mg capsules) will be administered as a single oral dose in the fasting state
Arm Title
Part 1: Tab SRT2104 (slow release)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 1: Tab SRT2104 (intermediate release)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 1: Tab SRT2104 (fast release)
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2A: SRT2104 500 mg single-dose
Arm Type
Experimental
Arm Description
500 mg SRT2104 (formulation selected from Part 1) will be administered as a single oral dose in the fed state.
Arm Title
Part 2B: SRT2104 single alternative dose
Arm Type
Experimental
Arm Description
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.
Arm Title
Part 2C: SRT2104 500 mg daily for 7 days
Arm Type
Experimental
Arm Description
500 mg SRT2104 (formulation selected from Part 1) will be administered daily for 7 days.
Intervention Type
Drug
Intervention Name(s)
Cap SRT2104
Intervention Description
Micronized free base in a 250 mg SRT2104 (active equivalents) capsule
Intervention Type
Drug
Intervention Name(s)
Tab SRT2104 slow release
Intervention Description
New 250 mg SRT2104 mesylate salt slow release tablet
Intervention Type
Drug
Intervention Name(s)
Tab SRT2104 intermediate release
Intervention Description
New 250 mg SRT2104 mesylate salt intermediate release tablet
Intervention Type
Drug
Intervention Name(s)
Tab SRT2104 fast release
Intervention Description
New 250 mg SRT2104 mesylate salt fast release tablet
Intervention Type
Drug
Intervention Name(s)
Selected formulations of SRT2104 from Part 1
Intervention Description
SRT2104 500 mg of selected formulation(s) from Part 1 in single-dose or daily for 7 days
Intervention Type
Drug
Intervention Name(s)
Selected formulations of SRT2104 from Part 1 single alternative dose
Intervention Description
SRT2104 single alternative dose (other than 500 mg, but not to exceed 2000 mg) of selected formulation(s) from Part 1
Primary Outcome Measure Information:
Title
Measure of variability in exposure-CVw
Description
The variability in exposure of SRT2104 will be assessed by calculating the within subject coefficient of variation (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.
Title
Measure of relative bioavailability-AUC
Description
Relative bioavailability of SRT2104 will be assessed by evaluating area under the curve (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.
Title
Measure of relative bioavailability-Cmax
Description
Relative bioavailability of SRT2104 will be assessed by measuring maximum observed plasma concentration (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.
Title
Measure of relative bioavailability-Tmax
Description
Relative bioavailability of SRT2104 will be assessed by measuring the time to reach maximum observed plasma concentration (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.
Title
Safety of SRT2104 as assessed by number of subjects with adverse events (AE)s
Description
Safety parameter will include recording number of AEs, throughout the study.
Time Frame
Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Title
Safety of SRT2104 as assessed by intensity of AEs
Description
Safety parameter will include recording of intensity of AEs, throughout the study.
Time Frame
Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Title
Safety of SRT2104 as assessed by type of AEs
Description
Safety parameter will include recording of type of AEs, throughout the study.
Time Frame
Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Title
Safety of SRT2104 as assessed by change from Baseline in heart rate
Description
Safety will be assessed by recording heart rate at Baseline and at end of the study.
Time Frame
Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Title
Safety of SRT2104 as assessed by change from Baseline in blood pressure
Description
Safety will be assessed by recording blood pressure at Baseline and at end of the study.
Time Frame
Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Title
Safety of SRT2104 as assessed by change from Baseline in temperature
Description
Safety will be assessed by recording temperature at Baseline and at end of the study.
Time Frame
Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Title
Safety of SRT2104 as assessed by change from Baseline in ECG readings
Description
Safety will be assessed by recording the electrocardiogram (ECG) readings at Baseline and at end of the study.
Time Frame
Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Title
Safety of SRT2104 as assessed by change from Baseline in clinical laboratory parameters
Description
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.
Time Frame
Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21225
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
Links:
URL
https://www.clinicalstudydatarequest.com
Description
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
Available IPD and Supporting Information:
Available IPD/Information Type
Annotated Case Report Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117041
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117041
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117041
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Dataset Specification
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117041
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117041
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117041
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://www.clinicalstudydatarequest.com
Available IPD/Information Identifier
117041
Available IPD/Information Comments
For additional information about this study please refer to the GSK Clinical Study Register

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

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