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

Healthy Clinical Trial

Official title:

A Single-center, Open-label, Single-sequence, 2-part Study to Investigate the Effect of 75 mg Macitentan Once Daily at Steady State on the Pharmacokinetics of Riociguat, Sildenafil, Rosuvastatin and Tadalafil in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04211272
• Other study ID #: CR108727
• Secondary ID: 2019-004001-2767
• Status: Completed
• Phase: Phase 1
• Start date: January 14, 2020
• Est. completion date: April 19, 2021

Study information

• Verified date: May 2022
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: April 19, 2021
• Est. primary completion date: April 19, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Macitentan
Macitentan will be administrated as film-coated tablet in Part A and Part B.
• Sildenafil
Sildenafil will be administrated as film-coated tablet in Part A.
• Riociguat
Riociguat will be administrated as film-coated tablet in Part A.
• Rosuvastatin
Rosuvastatin will be administrated as film-coated tablet in Part B.

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology Unit	Merksem

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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)	AUC(0-infinity) is defined as area under the plasma analyte concentration-time curve from time 0 to infinite time.	Up to 25 days
Secondary	Part A: Maximum Observed Plasma Analyte Concentration (Cmax) of Desmethyl-sildenafil, M1 and ACT-132577	Cmax is defined as the maximum observed plasma analyte concentration.	Up to 25 days
Secondary	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	AUC(0-t) is defined as area under the plasma analyte concentration-time curve from time 0 to time t of the last measured concentration above the lower limit of quantification (LLOQ), calculated according to the linear trapezoidal rule, using the measured concentration-time values above the LLOQ.	Up to 25 days
Secondary	Part A and Part B: Time to Reach Maximum Observed Plasma Analyte Concentration (Tmax) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin	Tmax is defined as actual sampling time to reach maximum observed plasma analyte concentration.	Up to 25 days
Secondary	Part A and Part B: Apparent Elimination Half-life (t1/2) of Sildenafil, Desmethyl-sildenafil, Riociguat, M1, Macitentan, ACT-132577, Rosuvastatin	t1/2 is defined as the time measured for the plasma concentration to decrease by 1 half of its original concentration. It is associated with the terminal slope of the semilogarithmic drug concentration-time curve, calculated as t1/2=0.693/ lambda(z).	Up to 25 days
Secondary	Part A and Part B: Trough Plasma Concentration (Ctrough) of Macitentan and ACT-132577	Ctrough is defined as the observed plasma concentration before dosing or at the end of the dosing interval.	Up to 25 days
Secondary	Part B: Number of Participants with Adverse Event as a Measure of Safety and Tolerability	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to Day 45