Clinical trial NCT01702493: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Keywords: SRT2104
Modified Release
Bioavailability
Crossover
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2012-10-08
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Measure of variability in exposure-CVw
timeFrame: 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.
measure: Measure of relative bioavailability-AUC
timeFrame: 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.
measure: Measure of relative bioavailability-Cmax
timeFrame: 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.
measure: Measure of relative bioavailability-Tmax
timeFrame: 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.
measure: Safety of SRT2104 as assessed by number of subjects with adverse events (AE)s
timeFrame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
measure: Safety of SRT2104 as assessed by intensity of AEs
timeFrame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
measure: Safety of SRT2104 as assessed by type of AEs
timeFrame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
measure: Safety of SRT2104 as assessed by change from Baseline in heart rate
timeFrame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
measure: Safety of SRT2104 as assessed by change from Baseline in blood pressure
timeFrame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
measure: Safety of SRT2104 as assessed by change from Baseline in temperature
timeFrame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
measure: Safety of SRT2104 as assessed by change from Baseline in ECG readings
timeFrame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
measure: Safety of SRT2104 as assessed by change from Baseline in clinical laboratory parameters
timeFrame: Part 1: 7 weeks; Part 2A: 4 weeks; Part 2B: 4 weeks; Part 2C: 5 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: