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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
47
Macitentan will be administrated as film-coated tablet in Part A and Part B.
Sildenafil will be administrated as film-coated tablet in Part A.
Riociguat will be administrated as film-coated tablet in Part A.
Clinical Pharmacology Unit
Merksem, Belgium
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.
Time frame: 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.
Time frame: Up to 25 days
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.
Time frame: Up to 25 days
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.
Time frame: 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
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.
Time frame: 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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Rosuvastatin will be administrated as film-coated tablet in Part B.
Tmax is defined as actual sampling time to reach maximum observed plasma analyte concentration.
Time frame: 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
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).
Time frame: Up to 25 days
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.
Time frame: Up to 25 days
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.
Time frame: Up to Day 45