A Study of Macitentan, in Healthy Japanese Male Participants

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo; Drug: Macitentan Dose 1; Drug: Macitentan Dose 2; Drug: Macitentan Dose 3

Study type: Interventional

Funder types: Industry

Identifiers

NCT04500808

CR108788

67896062PAH1005 (Other Identifier)

Details and patient eligibility

About

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).

Enrollment: 24 patients

Sex: Male

Ages: 20 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Other

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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24 participants in 3 patient groups

Part 1: Double Blind Phase

Experimental group

Description:

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.

Treatment:

Drug: Macitentan Dose 3

Drug: Macitentan Dose 2

Drug: Placebo

Drug: Macitentan Dose 1

Part 2: Open Label Phase: Treatment Sequence AB

Experimental group

Description:

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.

Treatment:

Drug: Macitentan Dose 3

Part 2: Open Label Phase: Treatment Sequence BA

Experimental group

Description:

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.

Treatment:

Drug: Macitentan Dose 3