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

NCT04211272 | Completed Phase 1

• 3 other identifiers: CR1087272019-004001-2767896062PAH1003
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Part A and Part B: Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of Sildenafil, Riociguat, Rosuvastatin

  AUC(0-infinity) is defined as area under the plasma analyte concentration-time curve from time 0 to infinite time.

  Up to 25 days

• Part A and Part B: Maximum Observed Plasma Analyte Concentration (Cmax) of Sildenafil, Riociguat, Rosuvastatin

  Cmax is defined as the maximum observed plasma analyte concentration.

  Up to 25 days

Secondary Outcomes (7)

• Part A: Area Under the Plasma Analyte Concentration-time Curve from Time Zero to Infinite Time (AUC[0-infinity]) of Desmethyl-sildenafil, M1 (Metabolite of Riociguat) and ACT-132577 (Metabolite of Macitentan)

  Up to 25 days

• Part A: Maximum Observed Plasma Analyte Concentration (Cmax) of Desmethyl-sildenafil, M1 and ACT-132577

  Up to 25 days

• Part A and Part B: Area Under the Plasma Analyte Concentration-time Curve from 0 to Time t of the Last Measured Concentration (AUC[0-t]) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin

  Up to 25 days

• Part A and Part B: Time to Reach Maximum Observed Plasma Analyte Concentration (Tmax) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin

  Up to 25 days

• Part A and Part B: Apparent Elimination Half-life (t1/2) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin

  Up to 25 days

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: Macitentan; Drug: Sildenafil; Drug: Riociguat

Part B: Macitentan + Substrate Drug (Rosuvastatin)

EXPERIMENTAL

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.

Drug: Macitentan; Drug: Rosuvastatin

Interventions

Macitentan DRUG

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

Also known as: JNJ-67896062-AAA

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

Sildenafil DRUG

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

Also known as: Revatio

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

Riociguat DRUG

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

Also known as: Adempas

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

Rosuvastatin DRUG

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

Also known as: Crestor

Part B: Macitentan + Substrate Drug (Rosuvastatin)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

MeSH Terms

Interventions

macitentan; Sildenafil Citrate; riociguat; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Pyrimidines

Study Officials

• Actelion Clinical Trial

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 23, 2019
• First Posted: December 26, 2019
• Study Start: January 14, 2020
• Primary Completion: April 19, 2021
• Study Completion: April 19, 2021
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

BE (1)