Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05433675 | A Study of Two Macitentan Formulations in Healthy Adult Participants | PHASE1 | COMPLETED | 28 | — | — | Jun 22, 2022 | Oct 3, 2022 | Mar 30, 2025 | 1 | Belgium |
| NCT05392530 | A Study of Two Different Test Formulations Compared to the Reference Formulation of Macitentan in Healthy Adult Participants | PHASE1 | COMPLETED | 23 | — | — | May 25, 2022 | Sep 14, 2022 | Mar 30, 2025 | 1 | Belgium |
| 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 | PHASE1 | COMPLETED | 40 | — | — | Feb 4, 2022 | May 14, 2022 | Mar 30, 2025 | 1 | United States |
| NCT04963439 | A Study of Two Macitentan Pediatric Formulations in Healthy Adult Participants | PHASE1 | COMPLETED | 16 | — | — | Jul 8, 2021 | Oct 5, 2021 | Mar 30, 2025 | 1 | Belgium |
| NCT04540744 | A Study of Macitentan/Tadalafil Combination Administered a Fixed-dose Combination Formulation Compared to the Reference Free Combination of Macitentan and Tadalafil | PHASE1 | COMPLETED | 18 | — | — | Apr 30, 2021 | Aug 30, 2021 | Mar 30, 2025 | 1 | Belgium |
| NCT04500808 | A Study of Macitentan, in Healthy Japanese Male Participants | PHASE1 | COMPLETED | 24 | — | — | Jul 21, 2020 | Dec 14, 2020 | Mar 30, 2025 | 1 | Japan |
| NCT04235270 | A Study of Macitentan and Tadalafil as a Fixed Dose Combination and the Free Combination in Healthy Adult Participants | PHASE1 | COMPLETED | 62 | — | — | Jan 17, 2020 | Jul 17, 2020 | Mar 30, 2025 | 1 | United States |
| NCT04211272 | A 2-part Study to Investigate the Effect of Macitentan in Healthy Male Participants | PHASE1 | COMPLETED | 47 | — | — | Jan 14, 2020 | Apr 19, 2021 | Mar 30, 2025 | 1 | Belgium |
| NCT02050802 | Study to Assess the Effect of Macitentan on the Electrocardiogram (ECG) in Healthy Male and Female Subjects | PHASE1 | COMPLETED | 64 | — | — | Aug 1, 2011 | Nov 1, 2011 | Feb 3, 2025 | - | — |
Cmax is defined as maximum observed plasma analyte concentration of macitentan.
AUC (0-last) is defined as area under the plasma analyte concentration versus time curve from time 0 to time of the last quantifiable (non-BQL) concentration of macitentan.
AUC (0-infinity) is defined as the area under the plasma analyte concentration-time curve from time 0 to infinite time of macitentan, calculated as the summation of AUC(0-last) and C(last)/lambda(z); where AUC(0-last) is area under the analyte concentration-time curve from time zero to last quantifiable time, Clast is the last observed measurable (non-BQL) plasma analyte concentration, and lambda(z) is apparent terminal elimination rate constant.
AUC(0-last) is defined as area under the plasma analyte concentration-time curve of macitentan from time zero to time of the last quantifiable (non-below quantification limit \[BQL\]) concentration.
Cmax is defined as the maximum observed plasma analyte concentration.
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.
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.
AUC (0-last) is defined as area under the plasma analyte concentration-time curve of macitentan from time zero to time of the last quantifiable (non-below quantification limit \[BQL\]) concentration, calculated by linear-linear trapezoidal summation.
AUC (0-infinity) is defined as area under the plasma analyte concentration-time curve of macitentan from time zero to infinite time, calculated as the sum of AUC (0-last) and C(last)/lambda(z), where AUC (0-last) is area under the plasma analyte concentration-time curve from time zero to last measurable concentration, C(last) is the last observed measurable (non-BQL) plasma analyte concentration and lambda(z) is apparent terminal elimination rate constant.
Cmax is defined as maximum observed plasma analyte concentration.
AUC(0-last) is the area under the plasma analyte concentration-time curve from time zero to time of the last quantifiable (non-below quantification limit \[non-BQL\]) concentration, calculated by linear-linear trapezoidal summation.
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.
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to that medicinal product. The following are the AEs of special interest in this study: Hypotension: symptomatic hypotension or potentially clinically meaningful decrease in blood pressure, Edema/fluid retention: clinically relevant signs and symptoms of edema and/or fluid retention, Hemoglobin decrease/anemia: events of hemoglobin decrease from baseline of greater than (\>) 20 gram per liter (g/L), Liver events: liver aminotransferase abnormalities.
A SAE is any AE that results in: death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect and is a suspected transmission of any infectious agent via a medicinal product, is medically important.
Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation) will be reported
Number of Participants with abnormalities in ECG variables such as: PR, QRS, QT, RR, and QT corrected Fridericia's formulae (QTcF) will be reported.
Change from baseline in body weight in kilograms as a part of physical examination will be reported.
Change from baseline in height in centimeters as a part of physical examination will be reported.
Plasma concentration of macitentan and its active metabolite (ACT-132577) will be reported.
Cmax is the maximum observed plasma analyte concentration.
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.
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.
Cmax is the maximum observed plasma analyte concentration.
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.
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.
AUC(0-infinity) is defined as area under the plasma analyte concentration-time curve from time 0 to infinite time.
Cmax is defined as the maximum observed plasma analyte concentration.
The QTcF interval was obtained directly from the Holter ECG monitoring.Triplicate ECG recordings were obtained from a 12-lead Holter recording device at various time points on Day 8. Baseline data were obtained from the pre-dose recording on Day 1 (from about 45 to 15 minutes prior to the morning dose). The QTcF interval is the QT interval (interval from beginning of the Q wave until end of the T wave) corrected for heart rate with Fridericia's formula (QTcF = QT/RR\^0.33 where RR is 60/heart rate)
| Arm | Type | Description |
|---|---|---|
| Treatment Sequence AB | EXPERIMENTAL | Participants will receive single oral dose of macitentan formulated as dispersible final market image (FMI) in fasted conditions (test) (Treatment A) in Intervention Period 1 followed by a single oral dose of film-coated opsumit tablet in fasted conditions (reference) (Treatment B) in Intervention Period 2 on Day 1. There will be washout period of at least 10 days between two period. |
| Treatment Sequence BA | EXPERIMENTAL | Participants will receive Treatment B in Intervention Period 1 followed Treatment A in Intervention Period 2 on Day 1. There will be washout period of at least 10 days between two period. |
| Treatment Sequence ABC | EXPERIMENTAL | Participants will receive single oral dose of final marketing image (FMI) candidate #1 of macitentan (Treatment A \[test\]) under fed condition in Treatment Period 1, followed by single oral dose of FMI candidate #2 of macitentan (Treatment B \[test\]) under fed conditions in Treatment Period 2, and then single oral dose of the reference formulation of macitentan (Treatment C) under fed conditions in Treatment Period 3. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses. |
| Treatment Sequence BCA | EXPERIMENTAL | Participants will receive Treatment B in Treatment Period 1 followed by Treatment C in Treatment Period 2, and then Treatment A in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses. |
| Treatment Sequence CAB | EXPERIMENTAL | Participants will receive Treatment C in Treatment Period 1 followed by Treatment A in Treatment Period 2, and then Treatment B in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses. |
| Treatment Sequence ACB | EXPERIMENTAL | Participants will receive Treatment A in Treatment Period 1 followed by Treatment C in Treatment Period 2, and then Treatment B in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses. |
| Treatment Sequence CBA | EXPERIMENTAL | Participants will receive Treatment C in Treatment Period 1 followed by Treatment B in Treatment Period 2, and then Treatment A in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses. |
| Treatment Sequence BAC | EXPERIMENTAL | Participants will receive Treatment B in Treatment Period 1 followed by Treatment A in treatment period 2, and then Treatment C in Treatment Period 3 on Day 1. The study intervention administrations will be separated by at least 14 days to allow adequate washout duration following the single doses. |
| Part 1: Double Blind Phase | EXPERIMENTAL | Participants will receive macitentan or matching placebo from Day 1 up to Day 13 under fed conditions and will be up-titrated starting with 2 once daily (QD) dosing of Dose 1 from Days 1 to 2 followed by 3 qd doses of Dose 2 of macitentan from Days 3 to 5, followed by qd doses of Dose 3 macitentan from Days 6 to 13. |
| Part 2: Open Label Phase: Treatment Sequence AB | EXPERIMENTAL | Participants will receive Dose 3 of macitentan under fasted conditions (Treatment A) in period 1 followed by Dose 3 of macitentan under fed condition (Treatment B) in period 2 on Day 1 with a washout phase of at least 14 days between the two treatment periods. |
| Part 2: Open Label Phase: Treatment Sequence BA | EXPERIMENTAL | Participants will receive Treatment B in period 1 followed by Treatment A in period 2 on Day 1 with a washout phase of at least 14 days between the two treatment periods. |
| 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. |
| 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. |
| Part A: Macitentan + Substrate Drug (Sildenafil/Riociguat) | EXPERIMENTAL | Participants will receive a single dose of film-coated tablet of sildenafil under fasted condition (Treatment A1), then riociguat under fasted condition (Treatment A2) followed by macitentan under fed condition (Treatment B1), then riociguat along with macitentan under fasted conditions followed by macitentan under fed conditions (Treatment B2) and then sildenafil along with macitentan under fasted condition (Treatment B3). Macitentan will be administered in an up-titration regimen. |
| Part B: Macitentan + Substrate Drug (Rosuvastatin) | EXPERIMENTAL | Participants will receive a single dose of film-coated tablet of rosuvastatin under fasted condition (Treatment A1), then macitentan under fed condition (Treatment B1) followed by rosuvastatin along with macitentan under fasted condition followed by macitentan under fed condition (Treatment B2). Macitentan will be administered in an up-titration regimen. Part B of the study will be conducted depending on the results of Part A and feedback from Health Authorities. |
| Treatment sequence BCAD | EXPERIMENTAL | Subjects received study medication in the sequence BCAD. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence ABDC | EXPERIMENTAL | Subjects received study medication in the sequence ABDC. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence DACB | EXPERIMENTAL | Subjects received study medication in the sequence DACB. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence CDBA | EXPERIMENTAL | Subjects received study medication in the sequence CDBA. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence DBAC | EXPERIMENTAL | Subjects received study medication in the sequence DBAC. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence ADCB | EXPERIMENTAL | Subjects received study medication in the sequence ADCB. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence CABD | EXPERIMENTAL | Subjects received study medication in the sequence CABD . Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Treatment sequence BCDA | EXPERIMENTAL | Subjects received study medication in the sequence BCDA. Treatment A: moxifloxacin positive control (3 placebo tablets once daily on Days 1-7, and on Day 8 moxifloxacin 400 mg tablet and 2 macitentan-matching placebo tablets). Treatment B: macitentan 10 mg (1 macitentan 10 mg tablet and 2 placebo tablets once daily on Days 1-8). Treatment C: macitentan 30 mg (3 macitentan 10 mg tablets once daily on Days 1-8). Treatment D: placebo (3 placebo tablets on Days 1-8). There was a wash-out period of at least 10 days between the last study drug administration of the previous treatment and the first study drug administration of the following treatment. |
| Name | Type | Description |
|---|---|---|
| Macitentan | DRUG | Macitentan dispersible and film-coated tablets will be administered orally as per assigned treatment sequence. |
| Macitentan 10 mg | DRUG | Macitentan 10mg tablet will be administered orally as per assigned treatment sequence. |
| Tadalafil 20 mg | DRUG | Tadalafil 20mg tablet will be administered orally as per assigned treatment sequence. |
| Macitentan 10 mg/Tadalafil 20mg FDC | DRUG | FDC of Macitentan 10 mg/Tadalafil 20 mg will be administered orally as single dose tablets. |
| FDC of macitentan/tadalafil (10 mg/20 mg) | DRUG | FDC of macitentan/tadalafil (10 mg/20 mg) tablet will be administered orally as per assigned treatment sequence. |
| Macitentan Dose 1 | DRUG | Participants will receive Dose 1 of macitentan tablet in Part 1. |
| Macitentan Dose 2 | DRUG | Participants will receive Dose 2 of macitentan tablet in Part 1. |
| Macitentan Dose 3 | DRUG | Participants will receive Dose 2 of macitentan tablet in Part 1 and 2. |
| Placebo | DRUG | Participants will receive matching placebo from Day 1 up to Day 13. |
| 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. |
| Tadalafil | DRUG | Tadalafil 40 mg tablet will be administered orally as free combination. |
| Sildenafil | DRUG | Sildenafil will be administrated as film-coated tablet in Part A. |
| Riociguat | DRUG | Riociguat will be administrated as film-coated tablet in Part A. |
| Rosuvastatin | DRUG | Rosuvastatin will be administrated as film-coated tablet in Part B. |
| Moxifloxacin 400 mg | DRUG | - |
| Macitentan 30 mg | DRUG | - |
Inclusion Criteria: * Healthy on the basis of physical examination, medical and surgical 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...