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| ID | Type | Description | Link |
|---|---|---|---|
| 67896062PAH1002 | Other Identifier | Actelion |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| Treatment Sequence ACB | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Macitentan 10 mg | Drug | Macitentan 10mg tablet will be administered orally as per assigned treatment sequence. |
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| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Actelion Clinical Trial | Actelion | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PRAHS | Salt Lake City | Utah | 84124 | United States |
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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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.
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| 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. |
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| 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. |
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| Tadalafil 20 mg | Drug | Tadalafil 20mg tablet will be administered orally as per assigned treatment sequence. |
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| Macitentan 10 mg/Tadalafil 20mg FDC | Drug | FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets. |
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(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) |
| 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) |
| 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) |
| 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) |
| 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) |
| 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) |
| ID | Term |
|---|---|
| C533860 | macitentan |
| D000068581 | Tadalafil |
| ID | Term |
|---|---|
| D002243 | Carbolines |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D026121 | Indole Alkaloids |
| D007211 | Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006575 | Heterocyclic Compounds, 3-Ring |
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