Clinical trial NCT04500808: A Study of Macitentan, in Healthy Japanese Male Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Pharmaceutical K.K.
Sponsor class: INDUSTRY
First posted: 2020-08-05
Enrollment: 24
Sex: MALE
Minimum age (years): 20
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Part 1: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Day 29
measure: Part 1: Number of Participants with Adverse Event of Special Interests (AESIs)
timeFrame: Up to Day 29
measure: Part 1: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to Day 29
measure: Part 1: Number of Participants with Clinical Laboratory Abnormalities
timeFrame: Up to Day 29
measure: Part 1: Number of Participants with Abnormalities in ECG Variables
timeFrame: Up to Day 29
measure: Part 1: Change from Baseline in Weight
timeFrame: Baseline, up to Day 29
measure: Part 1: Change from Baseline in Height
timeFrame: Baseline, up to Day 29
measure: Part 2: Plasma Concentration of Macitentan and its Active Metabolite (ACT-132577)
timeFrame: Predose, 3, 5, 7, 8, 9, 10, 12, 16, 24, 48, 72, 120, 168, and 240 hours post dose
Secondary outcomes:
measure: Part 1: Plasma Concentration of Macitentan and its Active Metabolite (ACT-132577)
timeFrame: Day 5 and Day 13 (predose,1, 3, 5, 7, 8, 9, 10, 12, and 16 hours postdose)
measure: Part 1: Plasma Endothelin-1 (ET-1) Concentrations
timeFrame: Up to Day 29
measure: Part 2: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Day 12
measure: Part 2: Number of Participants with Adverse Event of Special Interests (AESIs)
timeFrame: Up to Day 12
measure: Part 2: Number of Participants with Serious Adverse Events (SAEs)
timeFrame: Up to Day 12
measure: Part 2: Number of Participants with Clinical Laboratory Abnormalities
timeFrame: Up to Day 12
measure: Part 2: Number of Participants with Abnormalities in ECG Variables
timeFrame: Up to Day 12
measure: Part 2: Change from Baseline in Weight
timeFrame: Baseline, Up to Day 12
measure: Part 2: Change from Baseline in Height
timeFrame: Baseline, Up to Day 12
Other outcomes:
Locations:
city: Tokyo
country: Japan
facility: Sumida Hospital
Study officials:
affiliation: Janssen Pharmaceutical K.K.
name: Janssen Pharmaceutical K.K., Japan Clinical Trial
role: STUDY_DIRECTOR
References: