A Single-center, Open-label, Single-dose, Randomized, 2-way Crossover Phase 1 Study in Healthy Adult Participants to Assess the Relative Oral Bioavailability of the Combination of Macitentan/Tadalafil (10 mg/20 mg) Administered a Fixed-dose Combination Formulation Compared to the Reference Free Combination of 10 mg Macitentan (Opsumit®) and 20 mg Tadalafil (Adcirca®)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of Macitentan, its Metabolite ACT-132577, and Tadalafil
研究概览
简要总结
The purpose of this study is to assess the rate and extent of absorption of macitentan and tadalafil following administration of a single oral dose of a fixed-dose combination (FDC) of 10 milligram (mg)/20 mg macitentan/tadalafil (test), compared to the coadministration as a free combination (reference) of 10 mg macitentan and 20 mg tadalafil under fasted 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
- Treatment
- 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
- •Must sign an informed consent form (ICF) indicating they understand the purpose of, and procedures required for, the study and are willing to participate in the study, before starting any screening activities
- •Body mass index (BMI; weight [kg]/height^2 [m]^2) between 18.5 and 30.0 kilogram per meter square (kg/m^2) inclusive, and body weight not less than 50.0 kg at screening
- •Healthy on the basis of physical examination, 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 millimeter of Mercury (mmHg) (inclusive) and diastolic blood pressure (DBP) between 50 and 90 mmHg (inclusive) at screening, preferably measured on the right arm, supine after 5 minutes of rest and standing after 3 minutes
- •Twelve-lead electrocardiogram (ECG) with heart rate between 45 and 90 beats per minute (bpm) and without clinically relevant abnormalities, at the discretion of the investigator, measured after the participant is supine for at least 5 minutes, at screening
- •During the study (from the day of first study drug intake onwards) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after the last study drug intake, a male participant must agree: (a) to wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participant should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak); (b) not to donate sperm for the purpose of reproduction.
- •Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies
排除标准
- •Female participant who is breastfeeding at screening and/or plans to breastfeed throughout the study until 30 days after last study drug intake
- •Known allergies, hypersensitivity, or intolerance to any active substance or drugs of the same class, or any excipient of the drug formulation(s)
- •Values of hepatic aminotransferase (alanine aminotransferase and/or aspartate aminotransferase) greater than (>)1.5 * upper limit of normal at screening
- •Any loss of vision (permanent or transient blindness in 1 or both eyes, including ophthalmic migraine, transient ischemic attack, retinal artery/vein thrombosis)
- •Known hereditary degenerative retinal disorders, including retinitis pigmentosa
研究组 & 干预措施
Treatment Sequence AB
Participants will receive a single oral dose of fixed dose combination (FDC) of macitentan/tadalafil (10 milligram [mg]/20 mg) in fasted conditions (test) (Treatment A) in treatment period 1 followed by a single oral dose of a free combination of 10 mg macitentan and 20 mg tadalafil in fasted conditions (reference) (Treatment B) in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.
干预措施: FDC of macitentan/tadalafil (10 mg/20 mg) (Drug)
Treatment Sequence AB
Participants will receive a single oral dose of fixed dose combination (FDC) of macitentan/tadalafil (10 milligram [mg]/20 mg) in fasted conditions (test) (Treatment A) in treatment period 1 followed by a single oral dose of a free combination of 10 mg macitentan and 20 mg tadalafil in fasted conditions (reference) (Treatment B) in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.
干预措施: Macitentan 10 mg (Drug)
Treatment Sequence AB
Participants will receive a single oral dose of fixed dose combination (FDC) of macitentan/tadalafil (10 milligram [mg]/20 mg) in fasted conditions (test) (Treatment A) in treatment period 1 followed by a single oral dose of a free combination of 10 mg macitentan and 20 mg tadalafil in fasted conditions (reference) (Treatment B) in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.
干预措施: Tadalafil 20 mg (Drug)
Treatment Sequence BA
Participants will receive Treatment B in treatment period 1 followed by Treatment A in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.
干预措施: FDC of macitentan/tadalafil (10 mg/20 mg) (Drug)
Treatment Sequence BA
Participants will receive Treatment B in treatment period 1 followed by Treatment A in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.
干预措施: Macitentan 10 mg (Drug)
Treatment Sequence BA
Participants will receive Treatment B in treatment period 1 followed by Treatment A in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.
干预措施: Tadalafil 20 mg (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of Macitentan, its Metabolite ACT-132577, and Tadalafil
时间窗: Predose and up to 216 hours post dose (Up to Day 10)
AUC (0-infinity) is the area under the analyte concentration-time curve (AUC) from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) analyte concentration; and lambda(z) is apparent terminal elimination rate constant.
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan, its Metabolite ACT-132577, and Tadalafil
时间窗: Predose and up to 216 hours post dose (Up to Day 10)
Cmax is defined as maximum observed plasma analyte concentration.
Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of Macitentan, its Metabolite ACT-132577, and Tadalafil
时间窗: Predose and up to 216 hours post dose (Up to Day 10)
AUC(0-last) is the area under the plasma analyte concentration-time curve from time zero to time of the last quantifiable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
次要结局
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(Up to 8 weeks)