Evaluating the Effects of Tipranavir (With Ritonavir) Capsule and Liquid Formulation on Cytochrome P450 and P-glycoprotein Activity Using a Biomarker Cocktail in Healthy Human Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 34
- 主要终点
- Area under plasma concentration-time curve (AUC) at steady state
研究概览
简要总结
Primary: To quantify the influence of single-dose and steady-state tipranavir/ritonavir 500/200 mg on intestinal and hepatic cytochrome P450 (CYP) and P-glycoprotein (P-gp) biomarkers, as a means of predicting drug interactions. The AUCs for biomarkers caffeine, warfarin, omeprazole, dextromethorphan, midazolam, and digoxin will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent
- •Healthy subjects aged between 18 years and 45 years inclusive
- •Weighing at least 50 kg
- •Volunteers must be hospitalized on Days 1-4, 7-9, and 17-20 for pharmacokinetic assessments for each biomarker and TPV/r (Days 7-9 and 17-20)
- •Volunteers must be willing to complete all study-related activities
- •Each volunteer must have a valid social security number
- •Each volunteer must have acceptable medical history, physical examination and laboratory test
排除标准
- •History or presence of allergy to the study drugs or their components or drugs of their class, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation
- •Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance
- •History or diagnosis of any significant medical conditions: Including but not limited to gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hematological, psychiatric, neurological, oncological or hormonal disorders
- •Known elevated liver enzymes in past clinical trials with any compound (experimental or marketed)
- •Clinically relevant laboratory abnormalities (e.g. Hgb<11g/dL, Hct<30g/dL, total cholesterol >240mg/dL, triglycerides >500mg/dL, fasting glucose >130mg/dL, liver function tests >2.5x upper limit of normal, baseline international normalized ratio >1.2)
- •History of evidence of clinically significant hepatic, cardiac, pulmonary, endocrine, immunological, gastrointestinal, hematological, vascular or collagen disease
- •History of alcohol abuse or use of any illicit drugs
- •Unable to abstain from more than one beer or alcohol equivalent per day for the duration of the study
- •Use of tobacco products and/or history of smoking within the past 2 months
- •Pregnant or breast feeding
- •Sexually active women of childbearing age who do not use an acceptable barrier method of birth control
- •Hypersensitivity to caffeine, warfarin, vitamin K, omeprazole, dextromethorphan, midazolam, tipranavir, ritonavir or their excipients
- •Concomitant treatment with other experimental compounds
- •Concomitant administration of any prescription or over the counter medications known to alter P450 enzyme or P-gp activity
- •Concomitant administration of any prescription or over the counter medications known to be highly dependent on P450 or P-gp for clearance for which elevated plasma concentrations are known to be associated with serious toxicity
- •Concomitant administration of any food product known to alter P450 enzyme or P-gp activity such as grapefruit juice, Seville oranges
- •Concomitant administration of any drug that could affect bleeding (e.g., aspirin, clopidogrel, ticlopidine, warfarin, heparin, low-molecular weight heparin)
- •Concomitant administration of oral contraceptives (may be included with 7-day washout period)
- •Concomitant administration of any herbal medications
- •Inadequate venous access
- •Renal or hepatic insufficiency
- •Clinically unacceptable result at the screening physical examination
- •Use of investigational medications within 30 days before study entry
- •HIV-positive
- •Body Mass Index (BMI) > 30 kg/m²
研究组 & 干预措施
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Tipranavir capsule (Drug)
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Ritonavir capsule (Drug)
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Caffeine (Drug)
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Warfarin sodium (Drug)
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Vitamin K (Drug)
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Omeprazole (Drug)
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Dextromethorphan hydrobromide (Drug)
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Midazolam injection (Drug)
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Midazolam oral solution (Drug)
Treatment A
tipranavir (TPV) capsule + ritonavir (RTV) capsule + cocktail + digoxin oral
干预措施: Digoxin tablet (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Tipranavir capsule (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Caffeine (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Ritonavir capsule (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Caffeine (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Warfarin sodium (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Vitamin K (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Omeprazole (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Dextromethorphan hydrobromide (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Midazolam injection (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Midazolam oral solution (Drug)
Treatment B
TPV capsule + RTV capsule + cocktail + digoxin injection
干预措施: Digoxin injection (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Tipranavir solution (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Ritonavir capsule (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Caffeine (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Warfarin sodium (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Vitamin K (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Omeprazole (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Dextromethorphan hydrobromide (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Midazolam injection (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Midazolam oral solution (Drug)
Treatment C
TPV solution + RTV capsule + cocktail + digoxin oral
干预措施: Digoxin tablet (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Tipranavir solution (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Ritonavir capsule (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Warfarin sodium (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Vitamin K (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Omeprazole (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Dextromethorphan hydrobromide (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Midazolam injection (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Midazolam oral solution (Drug)
Treatment D
TPV solution + RTV capsule + cocktail + digoxin injection
干预措施: Digoxin injection (Drug)
结局指标
主要结局
Area under plasma concentration-time curve (AUC) at steady state
时间窗: up to 72 hours
次要结局
- Apparent terminal half-life (t1/2)(up to 72 hours)
- Change in biomarkers(baseline, up to 22 days)
- Plasma concentration after 12 hours (Cp12h)(12 hours)
- Maximum plasma concentration (Cmax)(up to 12 hours)
- Time of maximum concentration (Tmax)(up to 72 hours)
- Area under plasma concentration-time curve (AUC) after single dose(up to 72 hours)
- Change in enzyme activity(baseline, up to 22 days)