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| ID | Type | Description | Link |
|---|---|---|---|
| 67896062PAH1006 | Other Identifier | Janssen Research & Development, LLC |
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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 (Bioequivalence Part) | Experimental | Participants will receive Treatment A (single oral dose of an fixed dose combination [FDC] of macitentan/tadalafil [10 milligram [mg]/40 mg] in fasted conditions [test]) or Treatment B (single oral dose of a free combination of 10 mg macitentan and 40 mg tadalafil in fasted conditions [reference]) on Day 1 of Treatment Period 1 followed by Treatment B or Treatment A on Day 1 of Treatment Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 10 days. |
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| Group 2 (Food-effect Part) | Experimental | Participants will receive Treatment C (single oral dose of an FDC of macitentan/tadalafil [10 mg/40 mg] in fed conditions [test]) or Treatment D (single oral dose of an FDC of macitentan/tadalafil (10 mg/40 mg) in fasted conditions [reference]) on Day 1 of Treatment Period 1 followed by Treatment D or Treatment C on Day 1 of Treatment Period 2. Study drug intake in subsequent treatment periods will be separated by a washout period of at least 10 days. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| FDC of Macitentan and Tadalafil | Combination Product | Fixed dose combination (FDC) of 1 film-coated tablet containing 10 mg of macitentan and 40 mg of tadalafil will be administered orally. |
| Measure | Description | Time Frame |
|---|---|---|
| Group 1: Maximum Observed Plasma Analyte Concentration (Cmax) of Tadalafil | Cmax is the maximum observed plasma analyte concentration. | 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. | 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. | 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. | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Research & Development, LLC Clinical Trial | Janssen Research & Development, LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion | Tempe | Arizona | 85283 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34624174 | Derived | Csonka D, Fishman V, Natarajan J, Stieltjes H, Armas D, Dishy V, Perez Ruixo JJ. Bioequivalence and food effect of a fixed-dose combination of macitentan and tadalafil: Adaptive design in the COVID-19 pandemic. Pharmacol Res Perspect. 2021 Oct;9(5):e00846. doi: 10.1002/prp2.846. |
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The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
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| ID | Term |
|---|---|
| D000068581 | Tadalafil |
| C533860 | macitentan |
| ID | Term |
|---|---|
| D002243 | Carbolines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Macitentan | Drug | Macitentan 10 mg tablet will be administered orally as free combination. |
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| Tadalafil | Drug | Tadalafil 40 mg tablet will be administered orally as free combination. |
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| 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. | Up to 216 hours post dose (Up to Day 10) |
Clast is the last observed measurable (non-below quantification limit [non-BQL]) plasma analyte concentration. |
| 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. | 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). | 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. | 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. | 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. | 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. | Up to 6 weeks |
| D026121 |
| Indole Alkaloids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006575 | Heterocyclic Compounds, 3-Ring |