A 2-part Study to Investigate the Effect of Macitentan in Healthy Male Participants

NCT ID: NCT04211272

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-14
• Study Completion Date: 2021-04-19

Brief Summary

The purpose of this study is to evaluate the effect of macitentan at steady state on the pharmacokinetic (PK) of a single dose of riociguat and sildenafil (Part A); and rosuvastatin (Part B) when co-administered to healthy male participants under fasted conditions.

Conditions

Healthy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Part A: Macitentan + Substrate Drug (Sildenafil/Riociguat)

Participants will receive a single dose of film-coated tablet of sildenafil under fasted condition (Treatment A1), then riociguat under fasted condition (Treatment A2) followed by macitentan under fed condition (Treatment B1), then riociguat along with macitentan under fasted conditions followed by macitentan under fed conditions (Treatment B2) and then sildenafil along with macitentan under fasted condition (Treatment B3). Macitentan will be administered in an up-titration regimen.

Group Type: EXPERIMENTAL

Macitentan

Intervention Type: DRUG

Macitentan will be administrated as film-coated tablet in Part A and Part B.

Sildenafil

Intervention Type: DRUG

Sildenafil will be administrated as film-coated tablet in Part A.

Riociguat

Intervention Type: DRUG

Riociguat will be administrated as film-coated tablet in Part A.

Part B: Macitentan + Substrate Drug (Rosuvastatin)

Participants will receive a single dose of film-coated tablet of rosuvastatin under fasted condition (Treatment A1), then macitentan under fed condition (Treatment B1) followed by rosuvastatin along with macitentan under fasted condition followed by macitentan under fed condition (Treatment B2). Macitentan will be administered in an up-titration regimen. Part B of the study will be conducted depending on the results of Part A and feedback from Health Authorities.

Group Type: EXPERIMENTAL

Macitentan

Intervention Type: DRUG

Macitentan will be administrated as film-coated tablet in Part A and Part B.

Rosuvastatin

Intervention Type: DRUG

Rosuvastatin will be administrated as film-coated tablet in Part B.

Interventions

Macitentan

Macitentan will be administrated as film-coated tablet in Part A and Part B.

Intervention Type: DRUG

Sildenafil

Sildenafil will be administrated as film-coated tablet in Part A.

Intervention Type: DRUG

Riociguat

Riociguat will be administrated as film-coated tablet in Part A.

Intervention Type: DRUG

Rosuvastatin

Rosuvastatin will be administrated as film-coated tablet in Part B.

Intervention Type: DRUG

Other Intervention Names

JNJ-67896062-AAA; Revatio; Adempas; Crestor

Eligibility Criteria

Inclusion Criteria

• Male (according to their reproductive organs and functions assigned by chromosomal complement)
• Healthy on the basis of physical examination, medical history, and 12 lead electrocardiogram (ECG) performed at screening. This determination must be recorded in the participant's source documents and initialed by the investigator
• Body mass index (BMI; weight per height^2) between 18.0 and 30.0 kilogram (kg)/meter square (m^2) (inclusive), and body weight not less than 50.0 kg at screening and on Day -5
• Blood pressure (after the participant is supine for 5 minutes) between 100 and 140 millimeters of mercury (mmHg) systolic blood pressure (SBP), inclusive, and between 60 and 90 mmHg Diastolic blood pressure (DBP), inclusive, at screening and on Day -5. If blood pressure is out of range, up to 2 repeated assessments are permitted
• Heart rate between 45 and 90 beats per minute (bpm, inclusive) at screening and on Day -5

Exclusion Criteria

• History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
• Use of any prescription or nonprescription medication (including vitamins and herbal supplements), except for paracetamol (acetaminophen) within 14 days before the first dose of the study drug is scheduled until completion of the study
• A participant who has been on a known cytochrome P450 (CYP) inhibitor or inducer or transport inhibitor or inducer should be excluded from the study based upon the duration of the inhibitor or inductive effect and also at least 5 terminal half-lives of the drug, vitamin or herbal supplements
• Orthostatic hypotension (greater than [>] 20 mmHg decrease in SBP or >10 mmHg decrease in DBP after 2 minutes of standing compared to supine blood pressure)
• One or more of the following lab abnormalities at screening, defined as grade 1 or more by the World Health Organisation (WHO) Toxicity Grading Scale for Determining the Severity of Adverse Events, February 2003: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than or equal to (>=) 1.25 * upper limit of normal (ULN), total bilirubin >=1.25 * ULN, and Hemoglobin less than or equal to (<=) 10.5 gram per deciliter (g/dL)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• 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

Clinical Pharmacology Unit

Merksem, , Belgium

Countries

Belgium

Other Identifiers

2019-004001-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

67896062PAH1003

Identifier Type: OTHER

Identifier Source: secondary_id

CR108727

Identifier Type: -

Identifier Source: org_study_id