The purpose of this study is to demonstrate bioequivalence on the primary pharmacokinetic (PK) parameters of tadalafil administered as an fixed dose combination (FDC) (test) of macitentan/tadalafil (10 milligram \[mg\]/40 mg) and coadministered as a free combination (reference) of 10 mg macitentan (Opsumit) and 40 mg Canada-sourced tadalafil (Adcirca) in fasted conditions in healthy adult participants (Group 1) and to evaluate the effect of food on the primary PK parameters of macitentan and tadalafil administered as an FDC of macitentan/tadalafil (10 mg/40 mg) in healthy adult participants (Group 2).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
62
Fixed dose combination (FDC) of 1 film-coated tablet containing 10 mg of macitentan and 40 mg of tadalafil will be administered orally.
Macitentan 10 mg tablet will be administered orally as free combination.
Tadalafil 40 mg tablet will be administered orally as free combination.
Celerion
Tempe, Arizona, United States
Group 1: Maximum Observed Plasma Analyte Concentration (Cmax) of Tadalafil
Cmax is the maximum observed plasma analyte concentration.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 1: Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of Tadalafil
AUC(0-last) is the area under the plasma analyte concentration-time curve from time 0 to time of the last quantifiable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 1: Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of Tadalafil
AUC (0-infinity) is the area under the analyte concentration-time curve (AUC) from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) analyte concentration; and lambda(z) is apparent terminal elimination rate constant.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 2: Maximum Observed Plasma Analyte Concentration (Cmax) of Tadalafil and Macitentan
Cmax is the maximum observed plasma analyte concentration.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 2: Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUC [0-last]) of Tadalafil and Macitentan
AUC(0-last) is the area under the plasma analyte concentration-time curve from time 0 to time of the last quantifiable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 2: Area Under the Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of Tadalafil and Macitentan
AUC (0-infinity) is the area under the analyte concentration-time curve (AUC) from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z); wherein AUC (0-last) is area under the plasma concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) analyte concentration; and lambda(z) is apparent terminal elimination rate constant.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 1 and Group 2: Time to Reach Maximum Observed Plasma Analyte Concentration (Tmax) of Tadalafil and Macitentan
Tmax is the actual sampling time to reach the maximum observed plasma analyte concentration.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 1 and Group 2: Last Observed Measurable Plasma Analyte Concentration (Clast) of Tadalafil and Macitentan
Clast is the last observed measurable (non-below quantification limit \[non-BQL\]) plasma analyte concentration.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 1 and Group 2: Area Under the Plasma Analyte Concentration-time Curve from Time of 0 to 72 Hours Post Dosing (AUC[0-72h] of Tadalafil and Macitentan
AUC (0-72h) is the area under the plasma analyte concentration-time curve from time 0 to 72 hours postdose, calculated by linear-linear trapezoidal summation.
Time frame: Up to 72 hours post dose
Group 1 and Group 2: Apparent Terminal Elimination Half-life (t1/2) of Tadalafil and Macitentan
Apparent terminal elimination half-life is time measured for the plasma analyte concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 1 and Group 2: Apparent Terminal Elimination Rate Constant (Lambda[z]) of Tadalafil and Macitentan
Lambda(z) is first-order elimination rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 1 and Group 2: Total Apparent Oral Clearance (CL/F) of Tadalafil and Macitentan
Total apparent oral clearance is clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 1 and Group 2: Apparent Volume of Distribution (Vdz/F) of Tadalafil and Macitentan
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma analyte concentration of a drug. Apparent volume of distribution after oral dose (Vdz/F) is influenced by the fraction absorbed.
Time frame: Up to 216 hours post dose (Up to Day 10)
Group 1 and Group 2: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
An AE 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 6 weeks