Clinical trial NCT03215966: A Study to Compare the Macitentan-tadalafil Fixed Dose Combination Tablet Relative to the Concomitant Administration of the Reference Tablets of Macitentan and Tadalafil in Healthy Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Keywords: bioequivalence
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2017-07-12
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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).


Eligibility criteria: Key Inclusion Criteria:

* 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)

Key Exclusion Criteria:

* 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.

Primary outcomes:
measure: Maximum plasma concentration (Cmax) of macitentan and tadalafil
timeFrame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
measure: Area under the plasma concentration-time curve from 0 to time t [AUC(0-t)] of macitentan and tadalafil
timeFrame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
measure: Area under the plasma concentration-time curve to infinitiy [AUC(0-inf)] of macitentan and tadalafil
timeFrame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
Secondary outcomes:
measure: maximal plasma concentration (Cmax) of ACT-132577
timeFrame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
measure: Area under the plasma concentration-time curve from 0 to time t [AUC(0-t)] of ACT-132577
timeFrame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
measure: Area under the plasma concentration-time curve to infinity [AUC(0-inf)] of ACT-132577
timeFrame: Blood samples for pharmacokinetic evaluations are collected at selected time points from Baseline (pre-dose) to 216 hours post-dose of each study period
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: CRS Clinical Research Services Mannheim
Study officials:
affiliation: Actelion
name: JP Jones
role: STUDY_DIRECTOR
References: