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

NCT05236231 | Completed Phase 1 FDA Drug

• 2 other identifiers: CR10914067896062PAH1002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (3)

• 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)

• 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)

• 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 Outcomes (7)

• Time to Reach Maximum Observed Plasma Analyte Concentration (Tmax) of Macitentan and its Metabolite JNJ-68212820, Tadalafil

  Predose up to 216 hours (up to Day 10)

• 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)

  Predose up to 216 hours (up to Day 10)

• Apparent Elimination Half-Life (t1/2) of Macitentan and its Metabolite JNJ-68212820, Tadalafil

  Predose up to 216 hours (up to Day 10)

• Apparent Terminal Elimination Rate Constant (lambda z) of Macitentan and its Metabolite JNJ-68212820, Tadalafil

  Predose up to 216 hours (up to Day 10)

• Total Apparent Oral Clearance (CL/F) of Macitentan and its Metabolite JNJ-68212820, Tadalafil

  Predose up to 216 hours (up to Day 10)

Study Arms (6)

Treatment Sequence ABC

EXPERIMENTAL

Participants will receive single oral dose of fixed dose combination (FDC) of macitentan/tadalafil under fasting conditions in (test) (Treatment A) Treatment Period 1 followed by single oral dose of FDC of macitentan/tadalafil under fed conditions (test) (Treatment B) in Treatment Period 2 and then single oral dose of macitentan/tadalafil under fasting conditions (reference) (Treatment C) in Treatment Period 3 on Day 1 of each Treatment Period. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Drug: Macitentan 10 mg; Drug: Tadalafil 20 mg; Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Treatment Sequence BCA

EXPERIMENTAL

Participants will receive Treatment B in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Drug: Macitentan 10 mg; Drug: Tadalafil 20 mg; Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Treatment Sequence CAB

EXPERIMENTAL

Participants will receive Treatment C in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Drug: Macitentan 10 mg; Drug: Tadalafil 20 mg; Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Treatment Sequence ACB

EXPERIMENTAL

Participants will receive Treatment A in Treatment Period 1 followed by Treatment C in Treatment Period 2 and Treatment B in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Drug: Macitentan 10 mg; Drug: Tadalafil 20 mg; Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Treatment Sequence CBA

EXPERIMENTAL

Participants will receive Treatment C in Treatment Period 1 followed by Treatment B in Treatment Period 2 and Treatment A in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Drug: Macitentan 10 mg; Drug: Tadalafil 20 mg; Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Treatment Sequence BAC

EXPERIMENTAL

Participants will receive Treatment B in Treatment Period 1 followed by Treatment A in Treatment Period 2 and Treatment C in Treatment Period 3. There will be a wash-out period of at least 12 days between Day 1 of subsequent treatment period.

Drug: Macitentan 10 mg; Drug: Tadalafil 20 mg; Drug: Macitentan 10 mg/Tadalafil 20mg FDC

Interventions

Macitentan 10 mg DRUG

Macitentan 10mg tablet will be administered orally as per assigned treatment sequence.

Also known as: Opsumit, JNJ-67896062

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Tadalafil 20 mg DRUG

Tadalafil 20mg tablet will be administered orally as per assigned treatment sequence.

Also known as: Adcirca, JNJ-10291697

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Macitentan 10 mg/Tadalafil 20mg FDC DRUG

FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets.

Also known as: ACT-064992D

Treatment Sequence ABC; Treatment Sequence ACB; Treatment Sequence BAC; Treatment Sequence BCA; Treatment Sequence CAB; Treatment Sequence CBA

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Actelion: lead

Study Sites (1)

PRAHS

Salt Lake City, Utah, 84124, United States

Location

MeSH Terms

Interventions

macitentan; Tadalafil

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring

Study Officials

• Actelion Clinical Trial

  Actelion

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2022
• First Posted: February 11, 2022
• Study Start: February 4, 2022
• Primary Completion: May 13, 2022
• Study Completion: May 14, 2022
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)