Pharmacokinetic Study of the HCV Protease Inhibitor Bo-cePRevir and the Proton Pump Inhibitor OMeprazOle (PROMO)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- boceprevir concentrations
研究概览
简要总结
The objective of this study is to determine the effect of multiple dose omeprazole on the pharmacokinetics of boceprevir and vice versa.
Furthermore, the safety of steady state boceprevir combined with multiple dose omeprazole will be evaluated.
详细描述
It is known that some drugs can significantly influence the bioavailability of other drugs. For example the proton pump inhibitors decrease the absorption of some protease inhibitors used in HIV treatment or of some oral tyrosine kinase inhibitors used in oncology. Proton pump inhibitors increase the pH in the stomach and might therefore decrease the solubility of other drugs with decreased absorption as a consequence.
Boceprevir (BOC) is an Hepatitis C (HCV) NS3 serine protease inhibitor that has recently received FDA approval for the treatment of chronic HCV infection. The drug substance is slightly soluble in water and administration with food increases the oral bioavailability of BOC relative to the fasted state, by 40% to 60% based on AUC.
Omeprazole (OME) is the most frequently used proton pump inhibitor. It is the second most prescribed drug in The Netherlands, with 5 million prescriptions a year.
OME is metabolized by CYP2C19 and CYP3A4 and is known to induce CYP1A2 and inhibit CYP2C19. BOC is a potent inhibitor of CYP3A4/5 and is not metabolised by CYP1A2 or CYP2C19. No interaction on metabolism of BOC is expected. However, an increase of OME levels may be expected due to the inhibition of CYP3A4 by BOC.
As proton pump inhibitors are widely used it is relevant to know if a drug-drug interaction between proton pump inhibitors and BOC exists which might influence the bioavailability of BOC.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 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
- •Subject is at least 18 and not older than 55 years at screening.
- •Subject does not smoke more than 10 cigarettes, 2 cigars, or 2 pipes per day for at least 3 months prior to the first dosing.
- •Subject has a Quetelet Index (Body Mass Index) of 18 to 30 kg/m2, extremes included.
- •Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
- •Subject is in good age-appropriate health condition as established by medical history, physical examination, electrocardiography, results of biochemistry, haematology and urinalysis testing within 4 weeks prior to Day
- •Results of biochemistry, haematology and urinalysis testing should be within the laboratory's reference ranges. If laboratory results are not within the reference ranges, the subject is included on condition that the Investigator judges that the deviations are not clinically relevant. This should be clearly recorded.
- •Subject has a normal blood pressure and pulse rate, according to the Investigator's judgement.
排除标准
- •Documented history of sensitivity/idiosyncrasy to medicinal products or excipients.
- •Positive HIV test.
- •Positive hepatitis B or C test.
- •Pregnant female (as confirmed by an HCG test performed less than 4 weeks before Day 1) or breastfeeding female. Female subjects of childbearing potential without adequate contraception, e.g. hysterectomy, bilateral tubal ligation, (non-hormonal) intrauterine device, total abstinence, double barrier methods, or two years post-menopausal. They must agree to take precautions in order to prevent a pregnancy throughout the entire conduct of the trial.
- •Therapy with any drug (for two weeks preceding dosing), except for paracetamol.
- •Relevant history or presence of pulmonary disorders (especially COPD), cardiovascular disorders, neurological disorders (especially seizures and migraine), psychiatric disorders, gastro-intestinal disorders, renal and hepatic disorders, hormonal dis-orders (especially diabetes mellitus), coagulation disorders.
- •Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- •History of or current abuse of drugs, alcohol or solvents.
- •Inability to understand the nature and extent of the trial and the procedures required.
- •Participation in a drug trial within 60 days prior to the first dose.
- •Donation of blood within 60 days prior to the first dose.
- •Febrile illness within 3 days before Day 1.
研究组 & 干预措施
boceprevir
Boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 (BOC alone)
干预措施: boceprevir (Drug)
omeprazole
Omeprazole 40 mg QD for 5 consecutive days (OME alone)
干预措施: Omeprazole (Drug)
boceprevir+omeprazole
Omeprazole 40 mg QD for 5 consecutive days combined with boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 (BOC+OME)
干预措施: boceprevir (Drug)
boceprevir+omeprazole
Omeprazole 40 mg QD for 5 consecutive days combined with boceprevir 800 mg TID for 4 consecutive days + a single dose of 800 mg on Day 5 (BOC+OME)
干预措施: Omeprazole (Drug)
结局指标
主要结局
boceprevir concentrations
时间窗: AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h
to determine the effect of chronic use of omeprazole on the steady state pharmacokinetics of boceprevir
次要结局
- omeprazole concentrations(AUC: pre-dose, 0.5, 1. 1.5, 2, 2.5, 3, 4, 5, 6 and 8h)
- adverse events(entire study)