A Study of Macitentan, in Healthy Japanese Male Participants

Healthy Clinical Trial

Official title:

A Double-blind, Randomized, Placebo-controlled, Multiple-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Macitentan and an Open-label, Randomized, Crossover, Single-dose Study to Evaluate the Effect of Food on Macitentan Pharmacokinetics, in Healthy Japanese Adult Male Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04500808
• Other study ID #: CR108788
• Secondary ID: 67896062PAH1005
• Status: Completed
• Phase: Phase 1
• Start date: July 21, 2020
• Est. completion date: December 14, 2020

Study information

• Verified date: January 2021
• Source: Janssen Pharmaceutical K.K.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 14, 2020
• Est. primary completion date: December 14, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 55 Years

Eligibility

Inclusion Criteria:

• Be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator

• Blood pressure (after the participant is supine for 5 minutes) between 90 and 140 millimeter of mercury (mmHg) systolic, inclusive, and no higher than 90 mmHg diastolic

• A participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak. Recommended highly effective methods of contraception in this study for female partners of male participants to use in addition to the male participant wearing a condom during include: oral hormonal contraception, intrauterine device, intrauterine hormone-releasing system and bilateral tubal occlusion

• A participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum 90 Days after receiving the last dose of study intervention

• Nonsmoker or smoker habitually smokes no more than 10 cigarettes or equivalent of e-cigarettes, or 2 cigars, or 2 pipes of tobacco per day for at least 6 months before first study drug administration

Exclusion Criteria:

• History of or current clinically significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders (including any abnormal bleeding or blood dyscrasias), lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency (creatinine clearance below 80 (milliliter per minute) mL/min calculated using Cockcroft-Gault equation), thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results

• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study site as deemed appropriate by the investigator

• History of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin or malignancy, which is considered cured with minimal risk of recurrence)

• Known allergies, hypersensitivity, or intolerance to macitentan or its excipients

• Known allergy to heparin or history of heparin-induced thrombocytopenia

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Macitentan Dose 1
Participants will receive Dose 1 of macitentan tablet in Part 1.
• Macitentan Dose 2
Participants will receive Dose 2 of macitentan tablet in Part 1.
• Macitentan Dose 3
Participants will receive Dose 2 of macitentan tablet in Part 1 and 2.
• Placebo
Participants will receive matching placebo from Day 1 up to Day 13.

Locations

Country	Name	City	State
Japan	Sumida Hospital	Tokyo

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Pharmaceutical K.K.

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Part 1: Number of Participants with Clinical Laboratory Abnormalities	Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation) will be reported	Up to Day 29
Primary	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
Primary	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
Primary	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
Primary	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
Secondary	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)
Secondary	Part 1: Plasma Endothelin-1 (ET-1) Concentrations	Plasma ET-1 concentrations for macitentan and ACT-132577 will be reported.	Up to Day 29
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   To learn how to participate in this trial please click here.