A Phase I, Single-Center, Double-Blind, Randomized, Placebo-Controlled, Parallel-Arm Study of the Effects of Avanafil on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- VIVUS LLC
- 入组人数
- 24
- 主要终点
- Pharmacokinetics - PK parameters AUC, C-max and t-max of R-and S-warfarin
研究概览
简要总结
This study is designed to look into the effect of avanafil on blood levels of warfarin and to investigate its effect on prothrombin time/international normalized ratio (INR) in healthy men.
详细描述
The trial is a single-centre, double-blind, randomized, placebo-controlled, 2-way crossover drug interaction study with at least a 21-day washout period.
Each subject will participate in two sessions in which they will be randomized to receive either 200 mg of avanafil or matching placebo for 9 days. On Day 3 of each period, subjects will receive a single dose of warfarin (25 mg). Following the warfarin dose, pharmacokinetic and pharmacodynamic sampling will be taken over a period of 7 days. Subjects will be discharged on Day 10 following the end-of-period evaluation. There will be a washout of at least 21 days between the warfarin doses. The study medications will be administered with 240 mL of water following an overnight fast of at least 10 hours.
Blood samples (3 mL) for the assessment of R- and S-warfarin concentrations in plasma will be drawn on Day 3 prior to warfarin administration and 0.5, 1, 1.5, 2, 4, 6, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours after the warfarin administration.
Blood samples (3 mL) for the assessment of avanafil and/or metabolite concentrations will be drawn on Day 3 prior to avanafil (or placebo) administration and at 0.5, 1, and 2 hours post-dose.
Blood samples (4.5 mL) for the assessment of prothrombin time (PT) and international normalized ratio (INR) will be drawn at screening, check-in, on Day 3 prior to warfarin administration and at 6, 12, 24, 36, 48, 72, 96, 120, 144, and 168 hours post-dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •adult male subjects,
- •21 to 45 years of age,
- •must be medically healthy with no clinically significant screening results.
排除标准
- •history or clinical evidence of clinically relevant cardiovascular (including thromboembolic disorders), hepatic, renal, hematological, endocrine, pulmonary, gastrointestinal, psychiatric or neurological impairment;
- •any clinically significant laboratory abnormalities as judged by the investigator;
- •systolic blood pressure < 90 or >120 mmHg;
- •diastolic blood pressure < 50 or > 90 mmHg;
- •allergy to or previous adverse events with PDE5 inhibitors, warfarin or their constituents;
- •use of prescription or over-the-counter drugs that are known to interfere with metabolism by the cytochrome P450 3A4 enzyme within 30 days of screening;
- •use of any investigational drug within 30 days of screening; use of any prescription or over-the-counter drugs or herbal remedies within 14 days of screening;
- •history of alcohol or drug abuse within 18 months, history of smoking within 6 months;
- •positive urine alcohol and drug test;
- •positive serum cotinine test;
- •positive serology for HIV, HCV, HBsAg.
研究组 & 干预措施
Avanafil
干预措施: 200 mg Avanafil (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Pharmacokinetics - PK parameters AUC, C-max and t-max of R-and S-warfarin
时间窗: 24 hrs
Pharmacodynamics - Prothrombin time, INR values, and area under effect-time curve (AUEC) of prothrombin and INR on days 14 and 15
时间窗: 24 hours
次要结局
未报告次要终点