A Single Dose Randomized Five-Way Crossover Pharmacokinetics (PK) Study of Tadalafil Semi-Chewable (Gummy) Formulations in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 主要终点
- maximum plasma cetirizine concentration (Cmax)
研究概览
简要总结
This is a randomized, open-label, single-dose, five-period crossover, relative bioavailability study to evaluate tadalafil gummy 10mg and tadalafil oral tablets 10mg in healthy volunteers
详细描述
This is an open-label, single dose, randomized, five-period, crossover design study to evaluate the relative bioavailability of a single oral dose of tadalafil gummy 10 mg (Test) and tadalafil oral tablets 10 mg (Reference) under fasted conditions in healthy adult male and female subjects, and the impact on the bioavailability of tadalafil gummy sugar free 10 mg when administered with food, when administered with or without water, and when chewed or swallowed whole.
Each subject will receive tadalafil gummy (10 mg) or tadalafil tablet and thereby will be his/hers own control.
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
- None
入排标准
- 年龄范围
- 19 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •male 19-65 years of age;
- •Available to participate for the planned duration of the study;
- •Able and willing to complete the informed consent process;
- •Agree to have blood samples collected and stored for the study;
- •Agree not to use approved or experimental benign prostatic hyperplasia or erectile dysfunction treatments anytime during the course of the study;
- •Have not taken finasteride or dutasteride therapy, any other lower urinary tract symptom (LUTS) therapy or phosphodiesterase type 5 (PDE5) inhibitors for specified duration of time prior to the study;
- •Have not taken nitrates, alpha blockers, antihypertensives, alcohol, CYP3A4 inhibitors and CYP3A4 inducers for a specified duration of time prior to the study;
- •Have a prostate specific antigen (PSA) score within acceptable range defined for study or negative biopsy of the prostate for cancer within 12 months of the study.
排除标准
- •A condition in which repeated blood draws poses more than minimal risk for the subject such as hemophilia, other severe coagulation disorders or significantly impaired venous access;
- •A condition that requires active medical intervention or monitoring to avert serious danger to the subject's health or well-being;
- •subjects with dentures, partial dentures or braces, subjects with swallowing disorders and subjects who abuse drugs, alcohol or tobacco;
- •Currently taking nitrates or nitro compounds, alpha blockers, antihypertensives, alcohol, CYP3A4 inhibitors, CYP3A4 inducers;
- •Currently taking any medicines known to conflict with tadalafil;
- •History of urinary retention or lower urinary tract (bladder) stones 6 months before the start of the study;
- •History of bladder outlet obstruction or urethral obstruction due to stricture, valves, sclerosis, or tumor;
- •History of diabetes;
- •History of cardiac conditions including angina requiring certain treatment with nitrates, heart disease or coronary conditions including myocardial infarction, bypass surgery, angioplasty or stent placement for a specified time before starting the study;
- •Certain neurological conditions associated with bladder problems or injuries to the brain or spinal cord within a specified time before starting the study.
研究组 & 干预措施
Treatment A: Test
Single oral dose of tadalafil gummy 10 mg, chewed, administered with approximately 240 mL of room temperature water, under fasted conditions
干预措施: Tadalafil 10 MG (Drug)
Treatment B: Reference
Single oral dose of tadalafil oral tablets 10 mg, administered with approximately 240 mL of room temperature water, under fasted conditions
干预措施: Tadalafil 10 MG (Drug)
Treatment C: Test
Single oral dose of tadalafil gummy 10 mg, chewed, administered with approximately 240 mL of room temperature water, under fed conditions
干预措施: Tadalafil 10 MG (Drug)
Treatment D: Test
Single oral dose of tadalafil gummy 10 mg, chewed, administered with no water, under fasted conditions
干预措施: Tadalafil 10 MG (Drug)
Treatment E: Test
Single oral dose of tadalafil gummy 10 mg, swallowed whole, administered with approximately 240 mL of room temperature water, under fasted conditions
干预措施: Tadalafil 10 MG (Drug)
结局指标
主要结局
maximum plasma cetirizine concentration (Cmax)
时间窗: 96 hours
PK blood samples to measure plasma concentrations of tadalafil will be collected by direct venipuncture or by use of an indwelling cannula. Blood will be collected into tubes containing K2EDTA for determination of plasma tadalafil concentration at time 0 (within 60 minutes pre-dose), 10, 20 minute post-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 48, 72 and 96 hours post-dose. Plasma tadalafil concentrations will be listed at each time point by subject and summarized by treatment at each time point using descriptive statistics (n, mean, standard deviation (SD), Coefficient of variation (CV%), median, minimum and maximum values). Pharmacokinetic calculations will be performed based on actual time of blood sample collection, using non-compartmental methods with Phoenix WinNonlin Version 8.1 (Certara USA, Inc., Princeton, New Jersey, USA). Plots of mean concentrations of plasma tadalafil versus time will be generated and Cmax will be generated from the plot.
area under the plasma drug concentration versus time curve (AUC)
时间窗: 96 hours
AUC will be determined using non-compartmental analysis methods (Phoenix WinNonlin software, version 8.1 or higher, Certara USA Inc., Princeton, NJ). AUC will be calculated to the last measurable observation (AUC0-t) and extrapolated to infinity (AUC0 ∞).
次要结局
- time to Cmax (Tmax)(96 hours)
- terminal elimination rate constant (Kel).(96 hours)
- elimination half-life (t½)(96 hours)