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

Psoriasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01702493
• Other study ID #: 117041
• Status: Completed
• Phase: Phase 1
• First received: October 4, 2012
• Last updated: June 9, 2017
• Start date: October 30, 2012
• Est. completion date: December 5, 2012

Study information

• Verified date: June 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 5, 2012
• Est. primary completion date: December 5, 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• Cap SRT2104
Micronized free base in a 250 mg SRT2104 (active equivalents) capsule
• Tab SRT2104 slow release
New 250 mg SRT2104 mesylate salt slow release tablet
• Tab SRT2104 intermediate release
New 250 mg SRT2104 mesylate salt intermediate release tablet
• Tab SRT2104 fast release
New 250 mg SRT2104 mesylate salt fast release tablet
• 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
• 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

Locations

Country	Name	City	State
United States	GSK Investigational Site	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Sirtris, a GSK Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Measure of variability in exposure-CVw	The variability in exposure of SRT2104 will be assessed by calculating the within subject coefficient of variation (CVw).	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.
Primary	Measure of relative bioavailability-AUC	Relative bioavailability of SRT2104 will be assessed by evaluating area under the curve (AUC).	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.
Primary	Measure of relative bioavailability-Cmax	Relative bioavailability of SRT2104 will be assessed by measuring maximum observed plasma concentration (Cmax).	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.
Primary	Measure of relative bioavailability-Tmax	Relative bioavailability of SRT2104 will be assessed by measuring the time to reach maximum observed plasma concentration (Tmax).	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.
Primary	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.	Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Primary	Safety of SRT2104 as assessed by intensity of AEs	Safety parameter will include recording of intensity of AEs, throughout the study.	Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Primary	Safety of SRT2104 as assessed by type of AEs	Safety parameter will include recording of type of AEs, throughout the study.	Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Primary	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.	Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Primary	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.	Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Primary	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.	Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Primary	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.	Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Primary	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.	Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.

External 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.
•   Results for study 117041 can be found on the GSK Clinical Study Register.