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

Actelion Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Healthy Subjects

Treatments: Drug: Tadalafil (Adcirca®); Drug: Macitentan (Opsumit®); Combination Product: Macitentan / tadalafil FDC

Study type: Interventional

Funder types: Industry

Identifiers

NCT03215966

AC-077-103

Details and patient eligibility

About

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).

Enrollment: 38 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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38 participants in 2 patient groups

Sequence A/B

Experimental group

Description:

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

Treatment:

Combination Product: Macitentan / tadalafil FDC

Drug: Macitentan (Opsumit®)

Drug: Tadalafil (Adcirca®)

Sequence B/A

Experimental group

Description:

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

Treatment:

Combination Product: Macitentan / tadalafil FDC

Drug: Macitentan (Opsumit®)

Drug: Tadalafil (Adcirca®)