A Phase I, Single-Centre, Open-Label, Randomized, Four-Period Crossover Study to Assess the Effect of Food on the Pharmacokinetics of Avanafil, to Determine The Relative Bioavailability of Two Avanafil Tablet Formulations and to Investigate Dose Proportionality 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 of avanafil
研究概览
简要总结
This study will assess the effect of food on the pharmacokinetics of avanafil (Formulation II); determine the relative bioavailability of two avanafil tablet formulations (Formulation I versus Formulation II) and will investigate the dose-proportionality of Formulation II avanafil tablet.
详细描述
In this Phase I, single-centre, open-label, randomized, four-period crossover study, each eligible subject will be randomized to receive the 4 treatments in a 4-way crossover fashion. The 4 treatments are as follows:
- Treatment A: 2x100 mg Formulation II avanafil tablet, fasted
- Treatment B: 2x100 mg Formulation II avanafil tablet, fed
- Treatment C: 2x100 mg Formulation I avanafil tablet, fasted
- Treatment D: 1x50 mg Formulation II avanafil tablet, fasted Subjects will report to the study site on the evening before each treatment and will remain at the site until the 24-hour PK sample has been drawn. A single oral dose of avanafil tablets will be administered with 240 mL of water. A washout period of at least 5 days will occur between the treatments. Subjects in treatment groups A, C and D will fast at least 10 hours prior to and for at least 4 hours following dosing. Subjects in treatment group B will eat a standardized high fat breakfast 30 prior to dosing. Standard meals will be provided uniformly to all subjects at approximately 4 and 9 hours after dosing, and an evening snack will be provided approximately 12 - 13 hours after dosing. Blood samples for the determination of plasma avanafil and its metabolite concentrations will be obtained from each subject at 0 (30 minutes pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 8, 12, 18 and 24 hours post-dose in each treatment period.
Adverse events; laboratory evaluations; color vision testing (Treatment A only), electrocardiogram and physical examination, vital signs will be assessed at various times during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •adult male subjects,
- •18 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 >150 mmHg;
- •diastolic blood pressure < 50 or > 95 mmHg;
- •history of retinitis pigmentosa or nonarteritic anterior ischemic optic neuropathy; allergy to or previous adverse events with PDE5 inhibitors 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 prior to Day 1 in Period 1;
- •use of any investigational drug within 30 days or six half-lives, whichever is longer, prior to Day 1 in Period 1;
- •use of any prescription or over-the-counter drugs or herbal remedies within 14 days prior to Day 1 in Period 1;
- •history of alcohol or drug abuse within 18 months, history of smoking within 6 months;
- •positive urine alcohol test;
- •positive cotinine test, positive urine drug screen;
- •positive serology for HIV, HCV antibody, HBsAg.
研究组 & 干预措施
Treatment A
2x100 mg Formulation II avanafil tablet, fasted
干预措施: Avanafil (Drug)
Treatment B
2x100 mg Formulation II avanafil tablet, fed
干预措施: Avanafil (Drug)
Treatment C
2x100 mg Formulation I avanafil tablet, fasted
干预措施: Avanafil (Drug)
Treatment D
1x50 mg Formulation II avanafil tablet, fasted
干预措施: Avanafil (Drug)
结局指标
主要结局
Pharmacokinetics of avanafil
时间窗: April through May 2010
Cmax and AUC of avanafil in each period
次要结局
- Safety/AEs of avanafil(April through May, 2010)