A Phase 1, Open Label, Randomized, Four Period, Crossover, Multiple Dose Study To Assess The Pharmacokinetic Interaction Between Sitaxsentan and Tadalafil and The Effect Of Sildenafil On Sitaxsentan PK In Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax)
研究概览
简要总结
Sitaxsentan has a low drug-drug interaction potential and it did not have a clinically relevant effect on pharmacokinetics of sildenafil (a CYP3A sensitive substrate and PDE5 inhibitor).
Tadalafil did not have clinically relevant effect on pharmacokinetics of bosentan and ambrisentan. Based on overall clinical drug-drug interaction profiles, and in vitro CYP enzymes and transporter data, a clinically relevant drug-drug interaction between sitaxsentan and tadalafil is not expected. Sildenafil is not expected to affect sitaxsentan pharmacokinetics (PK), as sitaxsentan is a substrate of CYP3A4 and CYP2C9, where sildenafil did not show clinically relevant effect on PK of substrates of CYP3A4 and CYP2C9.
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
- 21 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects and women of non-child bearing potential between the ages of 21 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests.
- •Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >45 kg (99 lbs).
- •An informed consent document signed and dated by the subject or a legally acceptable representative.
- •Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing) or clinical findings at Screening.
- •A positive urine drug screen.
- •Subjects with hepatic dysfunction, defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) >1.5 times the upper limit of the normal range at Screening. A retest may be done if AST and/or ALT within 1.5- to 2- times the upper limit of the normal range at Screening, and the average of the first and repeated test values should be used to decide the eligibility.
研究组 & 干预措施
Treatment A
sitaxsentan 100 mg QD for 6 days (Treatment A)
干预措施: sitaxentan (Drug)
Treatment B
tadalafil 40 mg QD for 6 days
干预措施: tadalafil (Drug)
Treatment C
sitaxsentan 100 mg QD co-administered with tadalafil 40 mg QD for 6 days
干预措施: sitaxsentan (Drug)
Treatment C
sitaxsentan 100 mg QD co-administered with tadalafil 40 mg QD for 6 days
干预措施: tadalafil (Drug)
Treatment D
sitaxsentan 100 mg QD co-administered with sildenafil 20 mg TID for 6 days
干预措施: sitaxsentan (Drug)
Treatment D
sitaxsentan 100 mg QD co-administered with sildenafil 20 mg TID for 6 days
干预措施: sildenafil (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax)
时间窗: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Volume of Distribution at Steady State (Vss)
时间窗: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time to Reach Maximum Observed Plasma Concentration (Tmax)
时间窗: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Trough Plasma Concentrations (Ctrough)
时间窗: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Minimum or "trough"concentrations
Area Under the Curve of the 24 Hour Dosing Interval (AUC24)
时间窗: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Apparent Oral Clearance (CL/F)
时间窗: Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
次要结局
- Plasma Decay Half-Life (t1/2)(Day 6 (predose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, and 24 hours post dose))