A Single-center, Open-label, Four-period, Fixed-sequence Study to Investigate the Effect of Single and Repeated Oral Doses of ACT-539313 on the Pharmacokinetics of Flurbiprofen, Omeprazole, Midazolam, and Their Respective Metabolites in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Time to reach Cmax (tmax) of each probe substrate: flurbiprofen, midazolam and omeprazole.
研究概览
简要总结
A study to investigate the effect of single and repeated oral doses of ACT-539313 on what the body does to flurbiprofen, omeprazole, midazolam in healthy participants.
详细描述
A screening evaluation will be performed within 3 to 28 days (or within 10 to 28 days for women of childbearing potential) before first study treatment administration. Prior to any screening assessment, participants must sign the informed consent form.
Eligibility will be based on the results of the Screening and Day -1 assessments.
The participants will be confined to the study site from the morning of Day -1 until the morning of Day 2, from the morning of Day 7 until the morning of Day 9 and from the morning of Day 14 until the morning of Day 16. Participants will return to the study site for the End of Study examination on Day 17.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Other
- 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 in a language understandable to the participant prior to any study-mandated procedure.
- •Healthy male or female subjects aged between 18 and 45 years (inclusive) at Screening.
- •Body Mass Index of 18.5 to 28.0 kg/m2 (inclusive) at Screening.
- •Women of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on Day -
- •They must consistently and correctly use (from Screening, during the entire study, and for at least 30 days after study treatment intake) a highly effective method of contraception with a failure rate of < 1% per year, be sexually inactive, or have a vasectomized partner. If a hormonal contraceptive is used, it must have been initiated at least 1 month before treatment administration.
- •Women of non-childbearing potential, i.e., postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause, confirmed by a FSH test), with previous bilateral salpingectomy, bilateral salpingo-oophorectomy or hysterectomy, or with premature ovarian failure (confirmed by a specialist), XY genotype, Turner syndrome, uterine agenesis.
- •12-lead ECG (including QT: < 450 milliseconds [for males] and < 470 milliseconds [for females] without clinically relevant abnormalities, measured after 5 min in the supine position at Screening and on Day -1.
排除标准
- •Pregnant or lactating women.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
- •Clinically relevant findings in clinical laboratory tests (hematology, clinical chemistry, and urinalysis, i.e. outside the reference ranges (< 0.9 lower limit of normal and > 1.1 upper limit of normal; except for relevant hepatic parameters [Alanine Aminotransferase (ALT), Aspartate Aminotransferase Test (AST), bilirubin] which must not exceed the upper limit of normal), at Screening and on Day -
- •History of major medical or surgical disorders which, in the opinion of the investigator, are likely to interfere with the absorption, distribution, metabolism, or excretion of the study treatment(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed).
- •Acute, ongoing, recurrent, or chronic systemic disease with the ability to interfere with the evaluation of the study results.
- •Prior history of severe respiratory failure, acute respiratory depression, or sleep apnea.
- •Prior history of peptic ulcer disease and/or gastrointestinal bleeding.
- •Prior history of asthma, urticaria, or other allergic type reactions after taking acetylsalicylic acid or other NSAIDs.
- •History of cardiovascular thrombotic events (including myocardial infarction and stroke) and coronary artery bypass graft surgery.
- •Participation in a clinical study involving study treatment administered within 3 months (or 5 t 1/2 of the study treatment administered [whichever is longer]) prior to screening or in more than 4 clinical studies within 1 year prior to Screening.
- •Previous treatment with any prescribed medications (including vaccines) or over-the-counter (OTC) medications (including herbal medicines such as St. John's Wort, homeopathic preparations, vitamins, and minerals; with the exception of ibuprofen [1200 mg/day] or paracetamol [up to 1500 mg/day] up until Day -1) within 3 weeks (or 5 t1/2 [whichever is longer]) prior to first study treatment administration.
研究组 & 干预措施
ACT-539313 with or without a standard combination (probe substrate)
Treatment arm has 4 in-house treatment periods. In Treatment Period 1, participants will receive a single oral dose of the standardized combination (probe substrate: containing flurbiprofen [50 mg], midazolam [2 mg] and omeprazole 20 [mg]) on Day 1. Participants will be discharged from the study site on Day 2 and will be re-admitted on Day 7. In Treatment Period 2 (morning of Day 8) a first oral dose of 100 mg ACT-539313 will be administered. One hour later a single oral dose of the probe substrate will be administered. In the evening of Day 8, a second oral dose of 100 mg ACT-539313 will be administered. During Treatment Period 3 (morning of Day 9, ending on the evening of Day 14) oral doses of 100 mg ACT-539313 will be administered in the morning and evening. In Treatment Period 4 (Day 15), a single oral dose of 100 mg ACT-539313 together with the probe substrate will be administered. The participants will receive the last dose of ACT-539313 in the evening of Day 15.
干预措施: ACT-539313 (Drug)
ACT-539313 with or without a standard combination (probe substrate)
Treatment arm has 4 in-house treatment periods. In Treatment Period 1, participants will receive a single oral dose of the standardized combination (probe substrate: containing flurbiprofen [50 mg], midazolam [2 mg] and omeprazole 20 [mg]) on Day 1. Participants will be discharged from the study site on Day 2 and will be re-admitted on Day 7. In Treatment Period 2 (morning of Day 8) a first oral dose of 100 mg ACT-539313 will be administered. One hour later a single oral dose of the probe substrate will be administered. In the evening of Day 8, a second oral dose of 100 mg ACT-539313 will be administered. During Treatment Period 3 (morning of Day 9, ending on the evening of Day 14) oral doses of 100 mg ACT-539313 will be administered in the morning and evening. In Treatment Period 4 (Day 15), a single oral dose of 100 mg ACT-539313 together with the probe substrate will be administered. The participants will receive the last dose of ACT-539313 in the evening of Day 15.
干预措施: Flurbiprofen (Drug)
ACT-539313 with or without a standard combination (probe substrate)
Treatment arm has 4 in-house treatment periods. In Treatment Period 1, participants will receive a single oral dose of the standardized combination (probe substrate: containing flurbiprofen [50 mg], midazolam [2 mg] and omeprazole 20 [mg]) on Day 1. Participants will be discharged from the study site on Day 2 and will be re-admitted on Day 7. In Treatment Period 2 (morning of Day 8) a first oral dose of 100 mg ACT-539313 will be administered. One hour later a single oral dose of the probe substrate will be administered. In the evening of Day 8, a second oral dose of 100 mg ACT-539313 will be administered. During Treatment Period 3 (morning of Day 9, ending on the evening of Day 14) oral doses of 100 mg ACT-539313 will be administered in the morning and evening. In Treatment Period 4 (Day 15), a single oral dose of 100 mg ACT-539313 together with the probe substrate will be administered. The participants will receive the last dose of ACT-539313 in the evening of Day 15.
干预措施: Omeprazole (Drug)
ACT-539313 with or without a standard combination (probe substrate)
Treatment arm has 4 in-house treatment periods. In Treatment Period 1, participants will receive a single oral dose of the standardized combination (probe substrate: containing flurbiprofen [50 mg], midazolam [2 mg] and omeprazole 20 [mg]) on Day 1. Participants will be discharged from the study site on Day 2 and will be re-admitted on Day 7. In Treatment Period 2 (morning of Day 8) a first oral dose of 100 mg ACT-539313 will be administered. One hour later a single oral dose of the probe substrate will be administered. In the evening of Day 8, a second oral dose of 100 mg ACT-539313 will be administered. During Treatment Period 3 (morning of Day 9, ending on the evening of Day 14) oral doses of 100 mg ACT-539313 will be administered in the morning and evening. In Treatment Period 4 (Day 15), a single oral dose of 100 mg ACT-539313 together with the probe substrate will be administered. The participants will receive the last dose of ACT-539313 in the evening of Day 15.
干预措施: Midazolam (Drug)
结局指标
主要结局
Time to reach Cmax (tmax) of each probe substrate: flurbiprofen, midazolam and omeprazole.
时间窗: Pre-dose through to 24 hours post-dose.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
The area under the plasma concentration-time curve from zero to 24 hours (AUC0-24) of flurbiprofen, midazolam and omeprazole.
时间窗: Pre-dose through to 24 hours post-dose.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
Maximum plasma concentration (Cmax) of each probe substrate: flurbiprofen, midazolam and omeprazole.
时间窗: Pre-dose through to 24 hours post-dose.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
ACT-539313 trough plasma concentrations (Ctrough)
时间窗: Pre-dose through to 10 days after first dose.
In periods 2, 3 and 4 the plasma pharmacokinetic parameters of ACT-539313 will be measured prior to the next dose being administered in the morning.
The terminal elimination half-life (t½) of each probe substrate: flurbiprofen, midazolam and omeprazole.
时间窗: Pre-dose through to 24 hours post-dose.
In periods 1, 2 and 4 the plasma pharmacokinetic parameters of flurbiprofen, omeprazole, and midazolam will be derived by non-compartmental analysis of the plasma concentration-time profiles. Plasma pharmacokinetic samples will be collected at multiple predefined time points to analyze probe substrate: flurbiprofen, midazolam and omeprazole concentrations.
次要结局
未报告次要终点