A Study of Fixed Dose Combination of Macitentan/Tadalafil (10 mg/20 mg) Compared to the Reference Free Combination of Macitentan and Tadalafil in Healthy Adult Participants

NCT ID: NCT05236231

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-04
• Study Completion Date: 2022-05-14

Brief Summary

The purpose of this study is to demonstrate bioequivalence on the primary pharmacokinetic (PK) parameters between macitentan and tadalafil administered as a fixed dose combination (FDC) (test) of macitentan/tadalafil and the co- administered free combination (reference) of macitentan (Opsumit) and tadalafil (Adcirca) in fasted conditions in healthy adult participants; and to evaluate the effect of food on the primary PK parameters of macitentan and tadalafil administered as an FDC of macitentan/tadalafil in fed versus fasted conditions in healthy adult participants.

Conditions

Healthy

Study Design

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

Study Groups

Treatment Sequence ABC

Participants will receive single oral dose of fixed dose combination (FDC) of macitentan/tadalafil under fasting conditions in (test) (Treatment A) Treatment Period 1 followed by single oral dose of FDC of macitentan/tadalafil under fed conditions (test) (Treatment B) in Treatment Period 2 and then single oral dose of macitentan/tadalafil under fasting conditions (reference) (Treatment C) in Treatment Period 3 on Day 1 of each Treatment Period. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Group Type: EXPERIMENTAL

Macitentan 10 mg

Intervention Type: DRUG

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

Tadalafil 20 mg

Intervention Type: DRUG

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

Macitentan 10 mg/Tadalafil 20mg FDC

Intervention Type: DRUG

FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets.

Treatment Sequence BCA

Participants will receive Treatment B in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Group Type: EXPERIMENTAL

Macitentan 10 mg

Intervention Type: DRUG

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

Tadalafil 20 mg

Intervention Type: DRUG

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

Macitentan 10 mg/Tadalafil 20mg FDC

Intervention Type: DRUG

FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets.

Treatment Sequence CAB

Participants will receive Treatment C in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Group Type: EXPERIMENTAL

Macitentan 10 mg

Intervention Type: DRUG

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

Tadalafil 20 mg

Intervention Type: DRUG

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

Macitentan 10 mg/Tadalafil 20mg FDC

Intervention Type: DRUG

FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets.

Treatment Sequence ACB

Participants will receive Treatment A in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Group Type: EXPERIMENTAL

Macitentan 10 mg

Intervention Type: DRUG

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

Tadalafil 20 mg

Intervention Type: DRUG

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

Macitentan 10 mg/Tadalafil 20mg FDC

Intervention Type: DRUG

FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets.

Treatment Sequence CBA

Participants will receive Treatment C in Treatment Period 1 followed by Treatment B in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Group Type: EXPERIMENTAL

Macitentan 10 mg

Intervention Type: DRUG

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

Tadalafil 20 mg

Intervention Type: DRUG

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

Macitentan 10 mg/Tadalafil 20mg FDC

Intervention Type: DRUG

FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets.

Treatment Sequence BAC

Participants will receive Treatment B in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment C in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Group Type: EXPERIMENTAL

Macitentan 10 mg

Intervention Type: DRUG

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

Tadalafil 20 mg

Intervention Type: DRUG

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

Macitentan 10 mg/Tadalafil 20mg FDC

Intervention Type: DRUG

FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets.

Interventions

Macitentan 10 mg

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

Intervention Type: DRUG

Tadalafil 20 mg

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

Intervention Type: DRUG

Macitentan 10 mg/Tadalafil 20mg FDC

FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets.

Intervention Type: DRUG

Other Intervention Names

Opsumit; JNJ-67896062; Adcirca; JNJ-10291697; ACT-064992D

Eligibility Criteria

Inclusion Criteria

• Healthy on the basis of physical examination and medical history, performed at screening. If there are any abnormalities, they must be considered not clinically relevant and this determination must be recorded in the participant's source documents and initialed by the investigator
• Systolic blood pressure (SBP) between 100 and 145 millimeters of mercury (mm Hg) (inclusive), diastolic blood pressure (DBP) between 50 and 90 mm Hg (inclusive), and pulse rate between 45 and 90 beats per minute (inclusive) at screening, supine for at least 5 minutes and after 3 minutes of standing
• Twelve-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
• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after the last study intervention intake
• Willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion Criteria

• Known allergies, hypersensitivity, or intolerance to macitentan, tadalafil, or drug of the same class, or its excipients
• 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 intervention(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed)
• Veins unsuitable for intravenous puncture on either arm (example, veins that are difficult to locate, access, or puncture, and veins with a tendency to rupture during or after puncture)
• 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

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Actelion Clinical Trial

Role: STUDY_DIRECTOR

Actelion

Locations

PRAHS

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

67896062PAH1002

Identifier Type: OTHER

Identifier Source: secondary_id

CR109140

Identifier Type: -

Identifier Source: org_study_id