A Study of Fixed Dose Combination of Macitentan/Tadalafil (10 mg/20 mg) Compared to the Reference Free Combination of Macitentan and Tadalafil in Healthy Adult Participants

Healthy Clinical Trial

Official title:

A Single-center, Open-label, Single-dose, Randomized, 3-way Crossover Phase 1 Study in Healthy Adult Participants to Assess the Bioequivalence of the Combination of Macitentan/Tadalafil (10 mg/20 mg) Administered as a Fixed Dose Combination Formulation Compared to the Reference Free Combination of 10 mg Macitentan (Opsumit®) and 20 mg Tadalafil (Adcirca®) as Well as the Food Effect of the Fixed-dose Combination Formulation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05236231
• Other study ID #: CR109140
• Secondary ID: 67896062PAH1002
• Status: Completed
• Phase: Phase 1
• Start date: February 4, 2022
• Est. completion date: May 14, 2022

Study information

• Verified date: May 2024
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to demonstrate bioequivalence on the primary pharmacokinetic (PK) parameters between macitentan and tadalafil administered as a fixed dose combination (FDC) (test) of macitentan/tadalafil and the co- administered free combination (reference) of macitentan (Opsumit) and tadalafil (Adcirca) in fasted conditions in healthy adult participants; and to evaluate the effect of food on the primary PK parameters of macitentan and tadalafil administered as an FDC of macitentan/tadalafil in fed versus fasted conditions in healthy adult participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: May 14, 2022
• Est. primary completion date: May 13, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy on the basis of physical examination and medical history, performed at screening. If there are any abnormalities, they must be considered not clinically relevant and this determination must be recorded in the participant's source documents and initialed by the investigator

• Systolic blood pressure (SBP) between 100 and 145 millimeters of mercury (mm Hg) (inclusive), diastolic blood pressure (DBP) between 50 and 90 mm Hg (inclusive), and pulse rate between 45 and 90 beats per minute (inclusive) at screening, supine for at least 5 minutes and after 3 minutes of standing

• Twelve-lead electrocardiogram (ECG) without clinically relevant abnormalities, at the discretion of the investigator, measured after the participant is supine for at least 5 minutes, at screening

• A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of 30 days after the last study intervention intake

• Willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion Criteria:

• Known allergies, hypersensitivity, or intolerance to macitentan, tadalafil, or drug of the same class, or its excipients

• History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism, or excretion of the study intervention(s) (appendectomy and herniotomy allowed, cholecystectomy not allowed)

• Veins unsuitable for intravenous puncture on either arm (example, veins that are difficult to locate, access, or puncture, and veins with a tendency to rupture during or after puncture)

• Known hereditary degenerative retinal disorders, including retinitis pigmentosa

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Macitentan 10 mg
Macitentan 10mg tablet will be administered orally as per assigned treatment sequence.
• Tadalafil 20 mg
Tadalafil 20mg tablet will be administered orally as per assigned treatment sequence.
• Macitentan 10 mg/Tadalafil 20mg FDC
FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets.

Locations

Country	Name	City	State
United States	PRAHS	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan and its Metabolite JNJ-68212820, and Tadalafil.	Cmax is defined as the maximum observed plasma analyte concentration.	Predose up to 216 hours (up to Day 10)
Primary	Area Under the Plasma Analyte Concentration Time Curve of Macitentan, its Metabolite JNJ-68212820, and Tadalafil from Time Zero to Time of the Last Quantifiable Concentration (AUC [0-Last])	AUC (0-last) is defined as area under the plasma analyte concentration time curve of macitentan, its metabolite JNJ-68212820 and tadalafil from time 0 to the time of the last quantifiable (non-below quantification limit [non-BQL]) concentrations.	Predose up to 216 hours (up to Day 10)
Primary	Area Under the Plasma Concentration Time Curve of Macitentan and its Metabolite JNJ-68212820, and Tadalafil from Time Zero to Infinite time (AUC [0-Infinity])	AUC (0-infinity) is defined as area under the plasma concentration-time curve of macitentan and its metabolite JNJ-68212820, and tadalafil from time 0 to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z) where C(last) is the last observed measurable (non-BQL) plasma analyte concentration.	Predose up to 216 hours (up to Day 10)
Secondary	Time to Reach Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite JNJ-68212820, Tadalafil	Tmax is defined as actual sampling time to reach the maximum observed plasma analyte concentration.	Predose up to 216 hours (up to Day 10)
Secondary	Area Under the Plasma Concentration Versus Time Curve of Macitentan and its Metabolite JNJ-68212820, Tadalafil From Time Zero up to 72 Hours Post Dosing (AUC72h)	(AUC 0-72h) is defined as the area under the plasma concentration-time curve of macitentan and its metabolite JNJ-68212820, tadalafil from time 0 to 72 hours postdose, calculated by linear-linear trapezoidal summation.	Predose up to 216 hours (up to Day 10)
Secondary	Apparent Elimination Half-Life (t1/2) of Macitentan and its Metabolite JNJ-68212820, Tadalafil	t1/2 is defined as apparent elimination half-life calculated as 0.693/lambda(z).	Predose up to 216 hours (up to Day 10)
Secondary	Apparent Terminal Elimination Rate Constant (lambda z) of Macitentan and its Metabolite JNJ-68212820, Tadalafil	Apparent terminal elimination rate constant is estimated by linear regression using the terminal log-linear phase of the log-transformed concentration versus time curve.	Predose up to 216 hours (up to Day 10)
Secondary	Total Apparent Oral Clearance (CL/F) of Macitentan and its Metabolite JNJ-68212820, Tadalafil	CL/F is defined as total apparent oral clearance calculated as dose/AUC(0-infinity).	Predose up to 216 hours (up to Day 10)
Secondary	Apparent Volume of Distribution (Vd/F) of Macitentan and its Metabolite JNJ-68212820, Tadalafil	Vd/F is defined as apparent volume of distribution calculated as dose/(lambda(z) *AUC (0 to infinity).	Predose up to 216 hours (up to Day 10)
Secondary	Last Observed Measurable Plasma Concentration (Clast) of Macitentan and its Metabolite JNJ-68212820, Tadalafil	Clast is defined as the last observed measurable (non-BQL) plasma concentration of macitentan and its metabolite JNJ-68212820, Tadalafil.	Predose up to 216 hours (up to Day 10)