A Study of Macitentan/Tadalafil Combination Administered a Fixed-dose Combination Formulation Compared to the Reference Free Combination of Macitentan and Tadalafil

NCT ID: NCT04540744

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-30
• Study Completion Date: 2021-08-30

Brief Summary

The purpose of this study is to assess the rate and extent of absorption of macitentan and tadalafil following administration of a single oral dose of a fixed-dose combination (FDC) of 10 milligram (mg)/20 mg macitentan/tadalafil (test), compared to the coadministration as a free combination (reference) of 10 mg macitentan and 20 mg tadalafil under fasted conditions in healthy adult participants.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Sequence AB

Participants will receive a single oral dose of fixed dose combination (FDC) of macitentan/tadalafil (10 milligram \[mg\]/20 mg) in fasted conditions (test) (Treatment A) in treatment period 1 followed by a single oral dose of a free combination of 10 mg macitentan and 20 mg tadalafil in fasted conditions (reference) (Treatment B) in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.

Group Type: EXPERIMENTAL

FDC of macitentan/tadalafil (10 mg/20 mg)

Intervention Type: DRUG

FDC of macitentan/tadalafil (10 mg/20 mg) tablet will be administered orally as per assigned treatment sequence.

Macitentan 10 mg

Intervention Type: DRUG

Macitentan 10 mg tablet will be administered orally as a free combination as per assigned treatment sequence.

Tadalafil 20 mg

Intervention Type: DRUG

Tadalafil 20 mg tablet will be administered orally as a free combination as per assigned treatment sequence.

Treatment Sequence BA

Participants will receive Treatment B in treatment period 1 followed by Treatment A in treatment period 2 on Day 1. Study drug intake in subsequent treatment periods in an individual participant will be separated by a washout period of at least 10 days.

Group Type: EXPERIMENTAL

FDC of macitentan/tadalafil (10 mg/20 mg)

Intervention Type: DRUG

FDC of macitentan/tadalafil (10 mg/20 mg) tablet will be administered orally as per assigned treatment sequence.

Macitentan 10 mg

Intervention Type: DRUG

Macitentan 10 mg tablet will be administered orally as a free combination as per assigned treatment sequence.

Tadalafil 20 mg

Intervention Type: DRUG

Tadalafil 20 mg tablet will be administered orally as a free combination as per assigned treatment sequence.

Interventions

FDC of macitentan/tadalafil (10 mg/20 mg)

FDC of macitentan/tadalafil (10 mg/20 mg) tablet will be administered orally as per assigned treatment sequence.

Intervention Type: DRUG

Macitentan 10 mg

Macitentan 10 mg tablet will be administered orally as a free combination as per assigned treatment sequence.

Intervention Type: DRUG

Tadalafil 20 mg

Tadalafil 20 mg tablet will be administered orally as a free combination as per assigned treatment sequence.

Intervention Type: DRUG

Other Intervention Names

Opsumit; Adcirca; Opsumit; Adcirca

Eligibility Criteria

Inclusion Criteria

• Must sign an informed consent form (ICF) indicating they understand the purpose of, and procedures required for, the study and are willing to participate in the study, before starting any screening activities
• Body mass index (BMI; weight [kg]/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, 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
• Systolic blood pressure (SBP) between 100 and 145 millimeter of Mercury (mmHg) (inclusive) and diastolic blood pressure (DBP) between 50 and 90 mmHg (inclusive) at screening, preferably measured on the right arm, supine after 5 minutes of rest and standing after 3 minutes
• Twelve-lead electrocardiogram (ECG) with heart rate between 45 and 90 beats per minute (bpm) and without clinically relevant abnormalities, at the discretion of the investigator, measured after the participant is supine for at least 5 minutes, at screening
• During the study (from the day of first study drug intake onwards) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after the last study drug intake, a male participant must agree: (a) to wear a condom when engaging in any activity that allows for passage of ejaculate to another person (male participant should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak); (b) not to donate sperm for the purpose of reproduction.

Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies

Exclusion Criteria

• Female participant who is breastfeeding at screening and/or plans to breastfeed throughout the study until 30 days after last study drug intake
• Known allergies, hypersensitivity, or intolerance to any active substance or drugs of the same class, or any excipient of the drug formulation(s)
• Values of hepatic aminotransferase (alanine aminotransferase and/or aspartate aminotransferase) greater than (>)1.5 * upper limit of normal at screening
• Any loss of vision (permanent or transient blindness in 1 or both eyes, including ophthalmic migraine, transient ischemic attack, retinal artery/vein thrombosis)
• Known hereditary degenerative retinal disorders, including retinitis pigmentosa

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Clinical Pharmacology Unit

Merksem, , Belgium

Countries

Belgium

Other Identifiers

2020-000566-42

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

67896062PAH1001

Identifier Type: OTHER

Identifier Source: secondary_id

CR108794

Identifier Type: -

Identifier Source: org_study_id