A Single-center, Open-label, Single-dose, Randomized, 3-way Crossover Phase 1 Study in Healthy Adult Participants to Assess the Bioequivalence of the Combination of Macitentan/Tadalafil (10 mg/20 mg) Administered as a Fixed Dose Combination Formulation Compared to the Reference Free Combination of 10 mg Macitentan (Opsumit®) and 20 mg Tadalafil (Adcirca®) as Well as the Food Effect of the Fixed-dose Combination Formulation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Analyte Concentration Time Curve of Macitentan, its Metabolite JNJ-68212820, and Tadalafil from Time Zero to Time of the Last Quantifiable Concentration (AUC [0-Last])
研究概览
简要总结
The purpose of this study is to demonstrate bioequivalence on the primary pharmacokinetic (PK) parameters between macitentan and tadalafil administered as a fixed dose combination (FDC) (test) of macitentan/tadalafil and the co- administered free combination (reference) of macitentan (Opsumit) and tadalafil (Adcirca) in fasted conditions in healthy adult participants; and to evaluate the effect of food on the primary PK parameters of macitentan and tadalafil administered as an FDC of macitentan/tadalafil in fed versus 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
- 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 history, performed at screening. If there are any abnormalities, they must be considered not clinically relevant and 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 (mm Hg) (inclusive), diastolic blood pressure (DBP) between 50 and 90 mm Hg (inclusive), and pulse rate between 45 and 90 beats per minute (inclusive) at screening, supine for at least 5 minutes and after 3 minutes of standing
- •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
- •A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after the last study intervention intake
- •Willing and able to adhere to the lifestyle restrictions specified in this protocol
排除标准
- •Known allergies, hypersensitivity, or intolerance to macitentan, tadalafil, or drug of the same class, or its excipients
- •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)
- •Veins unsuitable for intravenous puncture on either arm (example, veins that are difficult to locate, access, or puncture, and veins with a tendency to rupture during or after puncture)
- •Known hereditary degenerative retinal disorders, including retinitis pigmentosa
研究组 & 干预措施
Treatment Sequence CAB
Participants will receive Treatment C in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg (Drug)
Treatment Sequence ABC
Participants will receive single oral dose of fixed dose combination (FDC) of macitentan/tadalafil under fasting conditions in (test) (Treatment A) Treatment Period 1 followed by single oral dose of FDC of macitentan/tadalafil under fed conditions (test) (Treatment B) in Treatment Period 2 and then single oral dose of macitentan/tadalafil under fasting conditions (reference) (Treatment C) in Treatment Period 3 on Day 1 of each Treatment Period. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg (Drug)
Treatment Sequence ABC
Participants will receive single oral dose of fixed dose combination (FDC) of macitentan/tadalafil under fasting conditions in (test) (Treatment A) Treatment Period 1 followed by single oral dose of FDC of macitentan/tadalafil under fed conditions (test) (Treatment B) in Treatment Period 2 and then single oral dose of macitentan/tadalafil under fasting conditions (reference) (Treatment C) in Treatment Period 3 on Day 1 of each Treatment Period. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Tadalafil 20 mg (Drug)
Treatment Sequence ABC
Participants will receive single oral dose of fixed dose combination (FDC) of macitentan/tadalafil under fasting conditions in (test) (Treatment A) Treatment Period 1 followed by single oral dose of FDC of macitentan/tadalafil under fed conditions (test) (Treatment B) in Treatment Period 2 and then single oral dose of macitentan/tadalafil under fasting conditions (reference) (Treatment C) in Treatment Period 3 on Day 1 of each Treatment Period. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg/Tadalafil 20mg FDC (Drug)
Treatment Sequence BCA
Participants will receive Treatment B in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg (Drug)
Treatment Sequence BCA
Participants will receive Treatment B in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Tadalafil 20 mg (Drug)
Treatment Sequence BCA
Participants will receive Treatment B in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg/Tadalafil 20mg FDC (Drug)
Treatment Sequence CAB
Participants will receive Treatment C in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Tadalafil 20 mg (Drug)
Treatment Sequence CAB
Participants will receive Treatment C in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg/Tadalafil 20mg FDC (Drug)
Treatment Sequence ACB
Participants will receive Treatment A in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg (Drug)
Treatment Sequence ACB
Participants will receive Treatment A in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Tadalafil 20 mg (Drug)
Treatment Sequence ACB
Participants will receive Treatment A in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg/Tadalafil 20mg FDC (Drug)
Treatment Sequence CBA
Participants will receive Treatment C in Treatment Period 1 followed by Treatment B in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg (Drug)
Treatment Sequence CBA
Participants will receive Treatment C in Treatment Period 1 followed by Treatment B in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Tadalafil 20 mg (Drug)
Treatment Sequence CBA
Participants will receive Treatment C in Treatment Period 1 followed by Treatment B in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg/Tadalafil 20mg FDC (Drug)
Treatment Sequence BAC
Participants will receive Treatment B in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment C in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg (Drug)
Treatment Sequence BAC
Participants will receive Treatment B in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment C in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Tadalafil 20 mg (Drug)
Treatment Sequence BAC
Participants will receive Treatment B in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment C in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.
干预措施: Macitentan 10 mg/Tadalafil 20mg FDC (Drug)
结局指标
主要结局
Area Under the Plasma Analyte Concentration Time Curve of Macitentan, its Metabolite JNJ-68212820, and Tadalafil from Time Zero to Time of the Last Quantifiable Concentration (AUC [0-Last])
时间窗: Predose up to 216 hours (up to Day 10)
AUC (0-last) is defined as area under the plasma analyte concentration time curve of macitentan, its metabolite JNJ-68212820 and tadalafil from time 0 to the time of the last quantifiable (non-below quantification limit \[non-BQL\]) concentrations.
Area Under the Plasma Concentration Time Curve of Macitentan and its Metabolite JNJ-68212820, and Tadalafil from Time Zero to Infinite time (AUC [0-Infinity])
时间窗: Predose up to 216 hours (up to Day 10)
AUC (0-infinity) is defined as area under the plasma concentration-time curve of macitentan and its metabolite JNJ-68212820, and tadalafil from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z) where C(last) is the last observed measurable (non-BQL) plasma analyte concentration.
Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan and its Metabolite JNJ-68212820, and Tadalafil.
时间窗: Predose up to 216 hours (up to Day 10)
Cmax is defined as the maximum observed plasma analyte concentration.
次要结局
- Time to Reach Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite JNJ-68212820, Tadalafil(Predose up to 216 hours (up to Day 10))
- Area Under the Plasma Concentration Versus Time Curve of Macitentan and its Metabolite JNJ-68212820, Tadalafil From Time Zero up to 72 Hours Post Dosing (AUC72h)(Predose up to 216 hours (up to Day 10))
- Total Apparent Oral Clearance (CL/F) of Macitentan and its Metabolite JNJ-68212820, Tadalafil(Predose up to 216 hours (up to Day 10))
- Apparent Elimination Half-Life (t1/2) of Macitentan and its Metabolite JNJ-68212820, Tadalafil(Predose up to 216 hours (up to Day 10))
- Apparent Terminal Elimination Rate Constant (lambda z) of Macitentan and its Metabolite JNJ-68212820, Tadalafil(Predose up to 216 hours (up to Day 10))
- Apparent Volume of Distribution (Vd/F) of Macitentan and its Metabolite JNJ-68212820, Tadalafil(Predose up to 216 hours (up to Day 10))
- Last Observed Measurable Plasma Concentration (Clast) of Macitentan and its Metabolite JNJ-68212820, Tadalafil(Predose up to 216 hours (up to Day 10))