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| ID | Type | Description | Link |
|---|---|---|---|
| 67896062PAH1005 | Other Identifier | Janssen Pharmaceutical K.K., Japan |
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The main purpose of this study is to evaluate the safety and tolerability after multiple-dose administrations of macitentan with titration regimen starting from Dose 1 once daily (qd) up to Dose 2 qd in Japanese healthy adult male participants (Part 1) and to evaluate the effect of food on pharmacokinetics of macitentan and its active metabolite (ACT-132577) in Japanese healthy adult male participants with macitentan Dose 3 tablet (Part 2).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Macitentan Dose 1 | Drug | Participants will receive Dose 1 of macitentan tablet in Part 1. |
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| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Number of Participants with Adverse Events (AEs) | 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. | Up to Day 29 |
| Part 1: Number of Participants with Adverse Event of Special Interests (AESIs) | 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. | Up to Day 29 |
| Part 1: Number of Participants with Serious Adverse Events (SAEs) | 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. | Up to Day 29 |
| Part 1: Number of Participants with Clinical Laboratory Abnormalities |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Plasma Concentration of Macitentan and its Active Metabolite (ACT-132577) | Plasma concentration of macitentan and its active metabolite (ACT-132577) will be reported. | Day 5 and Day 13 (predose,1, 3, 5, 7, 8, 9, 10, 12, and 16 hours postdose) |
| Part 1: Plasma Endothelin-1 (ET-1) Concentrations |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Janssen Pharmaceutical K.K., Japan Clinical Trial | Janssen Pharmaceutical K.K. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sumida Hospital | Tokyo | 130-0004 | Japan |
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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| Macitentan Dose 2 | Drug | Participants will receive Dose 2 of macitentan tablet in Part 1. |
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| Macitentan Dose 3 | Drug | Participants will receive Dose 2 of macitentan tablet in Part 1 and 2. |
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| Placebo | Drug | Participants will receive matching placebo from Day 1 up to Day 13. |
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Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation) will be reported
| Up to Day 29 |
| Part 1: Number of Participants with Abnormalities in ECG Variables | Number of Participants with abnormalities in ECG variables such as: PR, QRS, QT, RR, and QT corrected Fridericia's formulae (QTcF) will be reported. | Up to Day 29 |
| Part 1: Change from Baseline in Weight | Change from baseline in body weight in kilograms as a part of physical examination will be reported. | Baseline, up to Day 29 |
| Part 1: Change from Baseline in Height | Change from baseline in height in centimeters as a part of physical examination will be reported. | Baseline, up to Day 29 |
| Part 2: Plasma Concentration of Macitentan and its Active Metabolite (ACT-132577) | Plasma concentration of macitentan and its active metabolite (ACT-132577) will be reported. | Predose, 3, 5, 7, 8, 9, 10, 12, 16, 24, 48, 72, 120, 168, and 240 hours post dose |
Plasma ET-1 concentrations for macitentan and ACT-132577 will be reported. |
| Up to Day 29 |
| Part 2: Number of Participants with Adverse Events (AEs) | 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. | Up to Day 12 |
| Part 2: Number of Participants with Adverse Event of Special Interests (AESIs) | 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. | Up to Day 12 |
| Part 2: Number of Participants with Serious Adverse Events (SAEs) | 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. | Up to Day 12 |
| Part 2: Number of Participants with Clinical Laboratory Abnormalities | Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urine samples) will be reported | Up to Day 12 |
| Part 2: Number of Participants with Abnormalities in ECG Variables | Number of Participants with abnormalities in ECG variables such as: PR, QRS, QT, RR, and QT corrected Fridericia's formulae (QTcF) will be reported. | Up to Day 12 |
| Part 2: Change from Baseline in Weight | Change from baseline in body weight in kilograms as a part of physical examination will be reported. | Baseline, Up to Day 12 |
| Part 2: Change from Baseline in Height | Change from baseline in height in centimeters as a part of physical examination will be reported. | Baseline, Up to Day 12 |