A Study of Macitentan, in Healthy Japanese Male Participants

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

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).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Macitentan Dose 1; Drug: Macitentan Dose 2; Drug: Macitentan Dose 3; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan, 130-0004
    • Sumida Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Double Blind Phase; 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.	Drug: Macitentan Dose 1; Participants will receive Dose 1 of macitentan tablet in Part 1.; Other Names: JNJ-67896062; Drug: Macitentan Dose 2; Participants will receive Dose 2 of macitentan tablet in Part 1.; Other Names: JNJ-67896062; Drug: Macitentan Dose 3; Participants will receive Dose 2 of macitentan tablet in Part 1 and 2.; Other Names: JNJ-67896062; Drug: Placebo; Participants will receive matching placebo from Day 1 up to Day 13.
Experimental: Part 2: Open Label Phase: Treatment Sequence AB; 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.	Drug: Macitentan Dose 3; Participants will receive Dose 2 of macitentan tablet in Part 1 and 2.; Other Names: JNJ-67896062
Experimental: Part 2: Open Label Phase: Treatment Sequence BA; 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.	Drug: Macitentan Dose 3; Participants will receive Dose 2 of macitentan tablet in Part 1 and 2.; Other Names: JNJ-67896062

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Secondary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2020
• Primary Completion (Actual): December 14, 2020
• Study Completion (Actual): December 14, 2020

Study Registration Dates

• First Submitted: July 17, 2020
• First Submitted That Met QC Criteria: August 4, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Actual): January 14, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Endothelin Receptor Antagonists; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Macitentan
• Other Study ID Numbers: CR108788; 67896062PAH1005 (Other Identifier: Janssen Pharmaceutical K.K., Japan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No