A Study of Macitentan and Tadalafil as a Fixed Dose Combination and the Free Combination in Healthy Adult Participants

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Combination Product: FDC of Macitentan and Tadalafil; Drug: Tadalafil; Drug: Macitentan

Study type: Interventional

Funder types: Industry

Identifiers

NCT04235270

CR108735

67896062PAH1006 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to demonstrate bioequivalence on the primary pharmacokinetic (PK) parameters of tadalafil administered as an fixed dose combination (FDC) (test) of macitentan/tadalafil (10 milligram [mg]/40 mg) and coadministered as a free combination (reference) of 10 mg macitentan (Opsumit) and 40 mg Canada-sourced tadalafil (Adcirca) in fasted conditions in healthy adult participants (Group 1) and to evaluate the effect of food on the primary PK parameters of macitentan and tadalafil administered as an FDC of macitentan/tadalafil (10 mg/40 mg) in healthy adult participants (Group 2).

Enrollment: 62 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Body mass index (BMI; weight [kilogram]/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, and 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
• Healthy on the basis of clinical laboratory tests performed at screening. If the results of hematology, coagulation, or biochemistry assessments are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal 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), diastolic blood pressure (DBP) between 50 and 90 mmHg, and pulse rate between 45 and 99 beats per minute (bpm; inclusive), preferably measured on the right arm, after the participant is supine for at least 5 minutes, at screening
• 12-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

Exclusion criteria

• Female participant who is breastfeeding at screening and plans to breastfeed throughout the study
• Known allergy, hypersensitivity, or intolerance to any active substance or drugs of the same class, or any excipient 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) (appendectomy and herniotomy allowed, cholecystectomy not allowed)
• Any loss of vision in 1 or both eyes
• Known hereditary degenerative retinal disorders, including retinitis pigmentosa

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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62 participants in 2 patient groups

Group 1 (Bioequivalence Part)

Experimental group

Description:

Participants will receive Treatment A (single oral dose of an fixed dose combination \[FDC\] of macitentan/tadalafil \[10 milligram \[mg\]/40 mg\] in fasted conditions \[test\]) or Treatment B (single oral dose of a free combination of 10 mg macitentan and 40 mg tadalafil in fasted conditions \[reference\]) on Day 1 of Treatment Period 1 followed by Treatment B or Treatment A on Day 1 of Treatment Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 10 days.

Treatment:

Drug: Macitentan

Drug: Tadalafil

Combination Product: FDC of Macitentan and Tadalafil

Group 2 (Food-effect Part)

Experimental group

Description:

Participants will receive Treatment C (single oral dose of an FDC of macitentan/tadalafil \[10 mg/40 mg\] in fed conditions \[test\]) or Treatment D (single oral dose of an FDC of macitentan/tadalafil (10 mg/40 mg) in fasted conditions \[reference\]) on Day 1 of Treatment Period 1 followed by Treatment D or Treatment C on Day 1 of Treatment Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 10 days.

Treatment:

Drug: Macitentan

Drug: Tadalafil

Combination Product: FDC of Macitentan and Tadalafil