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Completed

NCT Number: NCT05236231

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

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.

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Key information

Conditions

Healthy

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

PRAHS

Salt Lake City, Utah, 84124, United States

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Macitentan 10 mg

Drug

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

Other names: Opsumit, JNJ-67896062

Tadalafil 20 mg

Drug

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

Other names: Adcirca, JNJ-10291697

Macitentan 10 mg/Tadalafil 20mg FDC

Drug

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

Other names: ACT-064992D

Primary outcomes

  1. Maximum Observed Plasma Analyte Concentration (Cmax) of Macitentan and its Metabolite JNJ-68212820, and Tadalafil.

    Time frame: Predose up to 216 hours (up to Day 10)

    Cmax is defined as the maximum observed plasma analyte concentration.

  2. 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])

    Time frame: Predose up to 216 hours (up to Day 10)

    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.

  3. 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])

    Time frame: Predose up to 216 hours (up to Day 10)

    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.

Secondary outcomes

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

    Time frame: Predose up to 216 hours (up to Day 10)

    Tmax is defined as actual sampling time to reach the maximum observed plasma analyte concentration.

  2. 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)

    Time frame: Predose up to 216 hours (up to Day 10)

    (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.

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

    Time frame: Predose up to 216 hours (up to Day 10)

    t1/2 is defined as apparent elimination half-life calculated as 0.693/lambda(z).

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

    Time frame: Predose up to 216 hours (up to Day 10)

    Apparent terminal elimination rate constant is estimated by linear regression using the terminal log-linear phase of the log-transformed concentration versus time curve.

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

    Time frame: Predose up to 216 hours (up to Day 10)

    CL/F is defined as total apparent oral clearance calculated as dose/AUC(0-infinity).

  6. Apparent Volume of Distribution (Vd/F) of Macitentan and its Metabolite JNJ-68212820, Tadalafil

    Time frame: Predose up to 216 hours (up to Day 10)

    Vd/F is defined as apparent volume of distribution calculated as dose/(lambda(z) *AUC (0 to infinity).

  7. Last Observed Measurable Plasma Concentration (Clast) of Macitentan and its Metabolite JNJ-68212820, Tadalafil

    Time frame: Predose up to 216 hours (up to Day 10)

    Clast is defined as the last observed measurable (non-BQL) plasma concentration of macitentan and its metabolite JNJ-68212820, Tadalafil.

Sponsors and collaborators

Lead sponsor

Actelion

Industry

Registry information

Official study 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

Important dates

Study start
2022
Primary completion
2022
Study completion
2022
First posted
Feb 11, 2022
Registry last updated
Mar 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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