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

NCT ID: NCT01702493

Last Updated: 2017-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-30
• Study Completion Date: 2012-12-05

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.

Conditions

Psoriasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Cap SRT2104

Intervention Type: DRUG

Micronized free base in a 250 mg SRT2104 (active equivalents) capsule

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.

Group Type: EXPERIMENTAL

Tab SRT2104 slow release

Intervention Type: DRUG

New 250 mg SRT2104 mesylate salt slow release tablet

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.

Group Type: EXPERIMENTAL

Tab SRT2104 intermediate release

Intervention Type: DRUG

New 250 mg SRT2104 mesylate salt intermediate release tablet

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.

Group Type: EXPERIMENTAL

Tab SRT2104 fast release

Intervention Type: DRUG

New 250 mg SRT2104 mesylate salt fast release tablet

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.

Group Type: EXPERIMENTAL

Selected formulations of SRT2104 from Part 1

Intervention Type: DRUG

SRT2104 500 mg of selected formulation(s) from Part 1 in single-dose or daily for 7 days

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.

Group Type: EXPERIMENTAL

Selected formulations of SRT2104 from Part 1 single alternative dose

Intervention Type: DRUG

SRT2104 single alternative dose (other than 500 mg, but not to exceed 2000 mg) of selected formulation(s) from Part 1

Part 2C: SRT2104 500 mg daily for 7 days

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

Group Type: EXPERIMENTAL

Selected formulations of SRT2104 from Part 1

Intervention Type: DRUG

SRT2104 500 mg of selected formulation(s) from Part 1 in single-dose or daily for 7 days

Interventions

Cap SRT2104

Micronized free base in a 250 mg SRT2104 (active equivalents) capsule

Intervention Type: DRUG

Tab SRT2104 slow release

New 250 mg SRT2104 mesylate salt slow release tablet

Intervention Type: DRUG

Tab SRT2104 intermediate release

New 250 mg SRT2104 mesylate salt intermediate release tablet

Intervention Type: DRUG

Tab SRT2104 fast release

New 250 mg SRT2104 mesylate salt fast release tablet

Intervention Type: 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

Intervention Type: 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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

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

Baltimore, Maryland, United States

Countries

United States

Study Documents

Document Type: Annotated Case Report 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: Clinical Study Report

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: Individual Participant Data Set

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: Statistical Analysis Plan

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

117041

Identifier Type: -

Identifier Source: org_study_id