A Single-center, Open-label, Single-dose, Randomized, 3-way Crossover Phase 1 Study in Healthy Adult Participants to Assess the Relative Oral Bioavailability of Macitentan 75 mg as Two Different Test Formulations Compared to the Reference Formulation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan
研究概览
简要总结
The purpose of this study is to assess the rate and extent of absorption of a single oral dose of macitentan given as 2 test formulations compared to the reference formulation under fed conditions in healthy adult participants.
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 on the basis of physical examination and medical and surgical history, performed at screening. If there are abnormalities, the participant may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator
- •Systolic blood pressure (SBP) between 100 and 145 millimeters of mercury (mmHg) (inclusive), diastolic blood pressure (DBP) between 50 and 90 mmHg (inclusive), and pulse rate between 45 and 90 beats per minute (inclusive), within 3 minutes after standing up and after the participant is supine for at least 5 minutes, at screening
- •Twelve-lead electrocardiogram (ECG) without clinically relevant abnormalities, at the discretion of the investigator, measured after the participant is supine for at least 5 minutes, at screening
- •Body weight not less than 50 kilograms (Kg) and body mass index (BMI; weight/height^2) within the range 18.5 -30 kg per meter square (kg/m^2) (inclusive)at screening
- •All women must have a negative highly sensitive serum (beta-human chorionic gonadotropin [beta-hCG]) pregnancy test at screening and a negative urine pregnancy test on Day -1 of the first treatment period
排除标准
- •Known allergies, hypersensitivity, or intolerance to any active substance or drugs of the same class, or any excipient of the drug formulation(s)
- •History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the study intervention(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed)
- •A history of repeated fainting due to cardiac cause, collapse, syncope, orthostatic hypotension, or vasovagal reactions
- •Female participant who is breastfeeding at screening and plans to breastfeed throughout the study
- •Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
研究组 & 干预措施
Treatment Sequence ABC
Participants will receive single oral dose of final marketing image (FMI) candidate #1 of macitentan (Treatment A [test]) under fed condition in Treatment Period 1, followed by single oral dose of FMI candidate #2 of macitentan (Treatment B [test]) under fed conditions in Treatment Period 2, and then single oral dose of the reference formulation of macitentan (Treatment C) under fed conditions in Treatment Period 3. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.
干预措施: Macitentan (Drug)
Treatment Sequence BCA
Participants will receive Treatment B in Treatment Period 1 followed by Treatment C in Treatment Period 2, and then Treatment A in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.
干预措施: Macitentan (Drug)
Treatment Sequence CAB
Participants will receive Treatment C in Treatment Period 1 followed by Treatment A in Treatment Period 2, and then Treatment B in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.
干预措施: Macitentan (Drug)
Treatment Sequence ACB
Participants will receive Treatment A in Treatment Period 1 followed by Treatment C in Treatment Period 2, and then Treatment B in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.
干预措施: Macitentan (Drug)
Treatment Sequence CBA
Participants will receive Treatment C in Treatment Period 1 followed by Treatment B in Treatment Period 2, and then Treatment A in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.
干预措施: Macitentan (Drug)
Treatment Sequence BAC
Participants will receive Treatment B in Treatment Period 1 followed by Treatment A in treatment period 2, and then Treatment C in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses.
干预措施: Macitentan (Drug)
结局指标
主要结局
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan
时间窗: Predose, up to 336 hours post dose (up to Day 15)
Cmax is defined as maximum observed plasma analyte concentration of macitentan.
Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Time of the Last Quantifiable Concentration of Macitentan (AUC[0-last])
时间窗: Predose, up to 336 hours post dose (up to Day 15)
AUC(0-last) is defined as area under the plasma analyte concentration-time curve of macitentan from time zero to time of the last quantifiable (non-below quantification limit \[BQL\]) concentration.
Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of Macitentan
时间窗: Predose, up to 336 hours post dose (up to Day 15)
AUC(0-infinity) is defined as area under the plasma analyte concentration-time curve of macitentan from time zero to infinite time.
次要结局
- Number of Participants with Serious Adverse Events (SAEs)(Up to 13 weeks)
- Last Observed Measurable Plasma Analyte Concentration (Clast) of Macitentan and its Metabolite Aprocitentan(Predose, up to 336 hours post dose (up to Day 15))
- Area Under the Plasma Analyte Concentration-time Curve of Macitentan and its Metabolite Aprocitentan from Time Zero to 72 Hours Post dose (AUC[0-72 Hours])(Predose, up to 336 hours post dose (up to Day 15))
- Area Under the Plasma Analyte Concentration-Time Curve from Time Zero to Time of the Last Quantifiable Concentration of Aprocitentan (AUC[0-last])(Predose, up to 336 hours post dose (up to Day 15))
- Maximum Observed Plasma Analyte Concentration (Cmax) of Aprocitentan(Predose, up to 336 hours post dose (up to Day 15))
- Apparent Terminal Elimination Half-life (t1/2) of Macitentan and its Metabolite Aprocitentan(Predose, up to 336 hours post dose (up to Day 15))
- Apparent Terminal Elimination Rate Constant (Lambda[z]) of Macitentan and its Metabolite Aprocitentan(Predose, up to 336 hours post dose (up to Day 15))
- Actual Sampling Time to Reach the Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite Aprocitentan(Predose, up to 336 hours post dose (up to Day 15))
- Total Apparent Oral Clearance (CL/F) of Macitentan(Predose, up to 336 hours post dose (up to Day 15))
- Apparent Volume of Distribution (Vdz/F) of Macitentan(Predose, up to 336 hours post dose (up to Day 15))
- Number of Participants with Abnormalities in Vital Signs(Up to Day 15)
- Area Under the Plasma Analyte Concentration-Time Curve of Aprocitentan from Time Zero to Infinity (AUC[0-infinity])(Predose, up to 336 hours post dose (up to Day 15))
- Number of Participants with Adverse Events (AEs)(Up to 13 weeks)
- Number of Participants with Abnormalities in Clinical Laboratory Tests(Up to Day 15)
- Number of Participants with Abnormalities in Physical Examination(Up to Day 15)
- Number of Participants with Abnormalities in Electrocardiograms (ECGs)(Up to Day 15)