临床试验/NCT01702493

NCT01702493已完成1 期

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

Sirtris, a GSK Company1 个研究点分布在 1 个国家目标入组 16 人开始时间: 2012年10月30日最近更新: 2017年6月12日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方
入组人数: 16
试验地点: 1
主要终点: Measure of relative bioavailability-AUC

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

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.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Other
盲法: None

入排标准

年龄范围: 18 Years 至 65 Years（Adult, Older Adult）
性别: Male
接受健康志愿者: 是

入选标准

•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) >=
•Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

排除标准

•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.

研究组 & 干预措施

Part 1: Cap SRT2104

Active Comparator

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

干预措施: Cap SRT2104 (Drug)

Part 1: Tab SRT2104 (slow release)

Experimental

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.

干预措施: Tab SRT2104 slow release (Drug)

Part 1: Tab SRT2104 (intermediate release)

Experimental

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.

干预措施: Tab SRT2104 intermediate release (Drug)

Part 1: Tab SRT2104 (fast release)

Experimental

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.

干预措施: Tab SRT2104 fast release (Drug)

Part 2A: SRT2104 500 mg single-dose

Experimental

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

干预措施: Selected formulations of SRT2104 from Part 1 (Drug)

Part 2B: SRT2104 single alternative dose

Experimental

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.

干预措施: Selected formulations of SRT2104 from Part 1 single alternative dose (Drug)

Part 2C: SRT2104 500 mg daily for 7 days

Experimental

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

干预措施: Selected formulations of SRT2104 from Part 1 (Drug)

结局指标

主要结局

Measure of relative bioavailability-AUC

时间窗: 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.

Relative bioavailability of SRT2104 will be assessed by evaluating area under the curve (AUC).

Measure of relative bioavailability-Tmax

Relative bioavailability of SRT2104 will be assessed by measuring the time to reach maximum observed plasma concentration (Tmax).

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-Cmax

Relative bioavailability of SRT2104 will be assessed by measuring maximum observed plasma concentration (Cmax).

Safety of SRT2104 as assessed by change from Baseline in heart rate