Single-center, Open-label, Single-dose, Two-period, Randomized, Crossover, Phase I Study to Demonstrate Bioequivalence Between a Fixed Dose Combination Product Formulation of Macitentan/Tadalafil (10 mg/40 mg) and the Free Combination of 10 mg Macitentan (Opsumit®) and 40 mg Tadalafil (Adcirca®) in Healthy Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Maximum plasma concentration (Cmax) of macitentan and tadalafil
研究概览
简要总结
The primary objective of this study is to demonstrate that macitentan and tadalafil administered as a fixed combination is bioequivalent to both compounds given as separate tablets given at the same doses as in the fixed combination (i.e. whether the amounts of macitentan and tadalfil which reach the blood are comparable).
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
- •Signed informed consent
- •Male and female subjects aged between 18 and 55 years (inclusive) at screening
- •Healthy on the basis of the physical examination, vital signs, 12-lead ECG, and laboratory tests performed at screening
- •Women must have a negative serum pregnancy test at screening and a negative urine pregnancy test on Day-1 or must be of non-childbearing potential.
- •Body mass index (BMI) of 18.0 to 30.0 kg/m2 (inclusive) at screening
- •Systolic blood pressure 100-145 mmHg, diastolic blood pressure 50-90 mmHg, and pulse rate 45-90 bpm (inclusive)
排除标准
- •Known hypersensitivity to any active substance or drugs of the same class, or any excipients 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 treatment(s)
- •Values of hepatic aminotransferase (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) > 3 X upper limit of normal at screening
- •Loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy
- •Known hereditary degenerative retinal disorders, including retinitis pigmentosa
- •Priapism and anatomical deformation of the penis
- •Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions
- •Treatment with another investigational drug within 3 months prior to screening or participation in more than 4 investigational drug studies within 1 year prior to screening
- •Excessive caffeine consumption, defined as > or = 800 mg per day at screening.
- •Nicotine intake (e.g., smoking, nicotine patch, nicotine chewing gum, or electronic cigarettes) within 3 months prior to screening and inability to refrain from nicotine intake from screening until end-of-study (EOS; washout period included)
- •Previous treatment with any prescribed medications (including vaccines) or over the counter (OTC) medications within 3 weeks prior to first study treatment administration.
- •Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
研究组 & 干预措施
Sequence A/B
Subjects receive one tablet of macitentan / tadalafil FDC (fixed dose combination) during Period 1, then after a washout period of at least 7 days they receive one tablet of macitentan (Opsumit®) and two tablets of tadalafil (Adcirca®) during Period 2
干预措施: Macitentan / tadalafil FDC (Combination Product)
Sequence A/B
Subjects receive one tablet of macitentan / tadalafil FDC (fixed dose combination) during Period 1, then after a washout period of at least 7 days they receive one tablet of macitentan (Opsumit®) and two tablets of tadalafil (Adcirca®) during Period 2
干预措施: Macitentan (Opsumit®) (Drug)
Sequence A/B
Subjects receive one tablet of macitentan / tadalafil FDC (fixed dose combination) during Period 1, then after a washout period of at least 7 days they receive one tablet of macitentan (Opsumit®) and two tablets of tadalafil (Adcirca®) during Period 2
干预措施: Tadalafil (Adcirca®) (Drug)
Sequence B/A
Subjects receive one tablet of macitentan (Opsumit®) and two tablets of tadalafil (Adcirca®) during Period 1, then after a washout period of at least 7 days, they receive one tablet of macitentan / tadalafil FDC (fixed dose combination) during Period 2
干预措施: Macitentan / tadalafil FDC (Combination Product)
Sequence B/A
Subjects receive one tablet of macitentan (Opsumit®) and two tablets of tadalafil (Adcirca®) during Period 1, then after a washout period of at least 7 days, they receive one tablet of macitentan / tadalafil FDC (fixed dose combination) during Period 2
干预措施: Macitentan (Opsumit®) (Drug)
Sequence B/A
Subjects receive one tablet of macitentan (Opsumit®) and two tablets of tadalafil (Adcirca®) during Period 1, then after a washout period of at least 7 days, they receive one tablet of macitentan / tadalafil FDC (fixed dose combination) during Period 2
干预措施: Tadalafil (Adcirca®) (Drug)
结局指标
主要结局
Maximum plasma concentration (Cmax) of macitentan and tadalafil
时间窗: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
The measured individual plasma concentrations of macitentan and tadalafil are used to directly obtain Cmax
Area under the plasma concentration-time curve from 0 to time t [AUC(0-t)] of macitentan and tadalafil
时间窗: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
AUC(0-t) is the area calculated from the concentration-time profile of macitentan and tadalafil, from time 0 to to time t of the last measured concentration above the limit of quantification
Area under the plasma concentration-time curve to infinitiy [AUC(0-inf)] of macitentan and tadalafil
时间窗: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
AUC(0-inf) is the area calculated from the concentration-time profile of macitentan and tadalafil, from time 0 to extrapolated infinite time
次要结局
- maximal plasma concentration (Cmax) of ACT-132577(Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period)
- Area under the plasma concentration-time curve from 0 to time t [AUC(0-t)] of ACT-132577(Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period)
- Area under the plasma concentration-time curve to infinity [AUC(0-inf)] of ACT-132577(Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period)