A Phase 1, Randomized, Open-label, 3-sequence, 4-treatment, Incomplete Block Design To Estimate The Effect Of Steady State Cyp3a4 Inhibitors (Itraconazole, Diltiazem Or Verapamil) On The Pharmacokinetics Of Singe Dose Pf-00489791 In Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax) of PF-00489791
研究概览
简要总结
The primary objective of the study is to estimate the effects of different strong enzyme (CYP3A4) inhibitors, itraconazole, diltiazem, or verapamil on the single dose pharmacokinetics of PF-00489791 in healthy volunteers. The study will enroll approximately 18 subjects that are randomized to 1 of 3 treatment groups. The study is also intended to determine the safety and tolerability of single-dose PF- 00489791 when it is administered with steady-state itraconazole, diltiazem, or verapamil.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and/or female subjects between the ages of 18 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) with a Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs.) and with a personally signed and dated informed consent document and who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Participating female subjects of non-childbearing potential must meet at least one of the following criteria: achieved postmenopausal status; have undergone a documented hysterectomy and/or bilateral oophorectomy; have medically confirmed ovarian failure. All other female subjects (including females with tubal ligations and females that do NOT have a documented hysterectomy, bilateral oophorectomy and/or ovarian failure) will be considered to be of childbearing potential.
排除标准
- •Subjects cannot be included in the study if there is: the presence/ history of any disorder that prevents study completion
- •Evidence/history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease
- •Any surgical or medical condition that may interfere with the absorption distribution, metabolism, or excretion of the study drug
- •A positive urine drug screen or history of regular excessive alcohol consumption or use of tobacco-or nicotine-containing products in excess or from 24-hours prior to admission until discharge
- •Treatment with an investigational drug within 30 days (or as determined by the local requirement) or 5 halflives preceding the first dose of study med.
- •Out of range blood pressure including current evidence of orthostatic change in blood pressure
- •Abnormal ECG or history or current evidence of clinically important cardiac conduction abnormalities.
- •Also excluded are: pregnant or breastfeeding female subjects; male subjects with partners currently pregnant; male and female subjects of childbearing potential who are unwilling or unable to use a highly effective method of contraception as described in the protocol for the duration of the study and for at least 28 days after the last dose of investigational product.
研究组 & 干预措施
Treatment B
Treatment B subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of itraconazole (200 mg once daily).
干预措施: itraconazole (Drug)
Treatment B
Treatment B subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of itraconazole (200 mg once daily).
干预措施: PF-00489791 (Drug)
Treatment C
Treatment C subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of diltiazem (240 mg once daily).
干预措施: diltiazem (Drug)
Treatment C
Treatment C subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of diltiazem (240 mg once daily).
干预措施: PF-00489791 (Drug)
Treatment D
Treatment D subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of verapamil (240 mg once daily).
干预措施: SR verapamil (Drug)
Treatment D
Treatment D subjects receive single dose administration of 20 mg PF-00489791 and multiple dose administration of verapamil (240 mg once daily).
干预措施: PF-00489791 (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax) of PF-00489791
时间窗: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-00489791
时间窗: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration
AUC is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption.
次要结局
- Apparent Oral Clearance (CL/F) of PF-00489791(Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration)
- Terminal Elimination Half-Life (t1/2) of PF-00489791(Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration)
- Apparent Volume of Distribution (Vz/F) of PF-00489791(Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration)
- Number of Participants With Potentially Clinically Significant Vital Signs Findings(Baseline up to Day 9)
- Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Findings(Pre-dose (Periods 1 and 2), 4, 72 and 96 hours post-dose in Period 2)
- Number of Participants Who Used at Least 1 Concomitant Medication(Baseline up to Day 15 (final study evaluation))
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-00489791(Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration)
- Number of Participants With Laboratory Abnormalities Meeting the Criteria for Potential Clinical Concern(Baseline up to 28 days after last study drug administration)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of PF-00489791(Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours after PF-00489791 administration)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)(Baseline up to 28 days after last study drug administration)