A Clinical Study to Find Out if Macitentan is Effective and Safe in Japanese Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH).

NCT03809650 | Terminated Phase 3

• 1 other identifier: AC-055E301
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 23

Brief Summary

The endothelin receptor antagonist macitentan showed significant improvement compared with placebo in pulmonary vascular resistance (PVR) and 6-minute walking distance (6MWD) in inoperable CTEPH patients in the phase II MERIT-1 trial (AC-055E201, NCT02021292). However, in the MERIT-1 trial Japanese patients were not included. Therefore, in line with Japan's medical environment, this phase III study is to confirm the efficacy and safety of macitentan in Japanese CTEPH patients.

Conditions

Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Keywords

CTEPH; chronic thromboembolic pulmonary hypertension; macitentan

Outcome Measures

Primary Outcomes (1)

• Evaluate the ratio in pulmonary vascular resistance (PVR) at rest from baseline to Week 16

  The resistance in the artery carrying blood to the lungs is called PVR. The PVR is the resistance in the artery carrying blood to the lungs and that has to be overcome by the right ventricle in heart in order to let blood flow to the lungs occur. The ratio in PVR at rest indicates the efficacy of macitentan in patients with CTEPH. The ratio in PVR at rest is calculated as PVR at Week 16 divided by baseline PVR. The ratio in PVR at rest from baseline to Week 16 of administration of macitentan is evaluated in subjects with CTEPH who are not indicated for pulmonary endarterectomy (PEA) and/or subjects who have postoperative persistent or recurrent pulmonary hypertension (PH) after PEA and/or balloon pulmonary angioplasty (BPA).

  From Baseline to Week 16

Secondary Outcomes (5)

• Change from baseline to Week 16 in PVR at rest

  From baseline to Week 16

• Change from baseline to Week 16 in pulmonary vascular resistance index (PVRI) at rest

  From baseline to Week 16

• Change from baseline to Week 24 in 6-minute walk distance (6MWD)

  From baseline to Week 24

• Change from baseline to Week 24 in Borg dyspnea index

  From baseline to Week 24

• Change from baseline to Week 24 in WHO functional class (WHO FC)

  From baseline to Week 24

Study Arms (1)

Open-label treatment period

EXPERIMENTAL

oral administration of macitentan 10 mg once daily

Drug: macitentan 10 mg

Interventions

macitentan 10 mg DRUG

macitentan 10 mg, film-coated tablet, oral use

Also known as: ACT-064992, Opsumit®

Open-label treatment period

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent to participate in the study obtained from the subject or legal representative a) prior to initiation of any study mandated procedure
• Japanese subjects who have been diagnosed as having CTEPH:
• Subjects who have not undergone balloon pulmonary angioplasty (BPA) and for whom the investigator determines not to implement pulmonary endarterectomy (PEA) at the time of the acquisition of informed consent due to the organized thrombosis localized in the peripheral regions, high risk (complications, old age, etc.) or for any other reasons.
• Subjects who have postoperative persistent or recurrent pulmonary hypertension (PH) after undergoing pulmonary endarterectomy (PEA) and/or BPA.
• PH subjects whose WHO FC is I to IV
• MWD measured during the screening period ranges from 150 m to 450 m
• Subjects who meet the following conditions according to the right heart catheterization (RHC) performed during the screening period or within 8 weeks before the acquisition of the informed consent:
• Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg
• Pulmonary artery wedge pressure (PAWP) ≤ 15 mmHg (if PAWP cannot be measured or the value of PAWP is not reliable, left ventricular end-diastolic pressure ≤ 13 mmHg)
• Resting PVR ≥ 400 dyn\*sec/cm5
• Subjects treated with anti-coagulation agents, unfractionated heparin or low molecular weight heparin at least 90 days prior to RHC at baseline
• Women with childbearing potential with negative serum pregnancy test results and able to follow the appropriate contraceptive methods from the date of starting the study drug administration up to 30 days after the discontinuation or completion of the study drug administration. Fertile male subjects able to use condom during the same period.

You may not qualify if:

• BPA within 90 days prior to undergoing baseline RHC
• PEA within 180 days prior to undergoing baseline RHC
• Subjects with unstable pulmonary hemodynamics who have postoperative persistent or recurrent PH after undergoing PEA and/or BPA
• Recurrent thromboembolism undergoing treatment with oral anti-coagulation agents
• Symptomatic acute pulmonary embolism within 180 days prior to the start of study drug administration
• Known moderate-to-severe restrictive lung disease or obstructive lung disease or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema)
• Acute myocardial infarction during Screening period
• Severe liver impairment.
• Systolic blood pressure (SBP) \< 90 mmHg at screening.
• Any known factor or disease that may interfere with treatment compliance or full participation in the study

Sponsors & Collaborators

• Actelion: lead
• EPS Corporation: collaborator
• Imepro Inc.: collaborator
• General Laboratory, BML, Inc.: collaborator
• Mitsubishi Logistics Corporation: collaborator

Study Sites (23)

Fukuoka University Nishijin Hospital

Fukuoka, 814-8522, Japan

Location

Fukushima Medical University Hospital

Fukushima, 960-1247, Japan

Location

Kagoshima University Hospital

Kagoshima, 890-8520, Japan

Location

Nara Medical University Hospital

Kashihara, 634-8522, Japan

Location

Kokura Kinen Hospital

Kitakyushu, 802-8555, Japan

Location

Kobe University Hospital

Kobe, 650-0017, Japan

Location

Saitama Cardiovascular and Respiratory Center

Kumagaya, 360-0197, Japan

Location

Kure Kyosai Hospital

Kure, 737-8505, Japan

Location

Kurume University Hospital

Kurume, 830-0011, Japan

Location

Toho University Ohashi Medical Center

Meguro-ku, 153-8515, Japan

Location

IIUHW Mita Hospital

Minatoku, 108-8329, Japan

Location

Kyorin University Hospital

Mitaka, 181-8611, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

National Hospital Organization Okayama Medical Center

Okayama, 701-1192, Japan

Location

Sapporo Medical University Hospital

Sapporo, 060-8543, Japan

Location

Hokkaido University Hospital

Sapporo, 060-8648, Japan

Location

Sasebo City General Hospital

Sasebo, 857-8511, Japan

Location

Keio University Hospital

Shinjuku-ku, 160-0016, Japan

Location

National Cerebral and Cardiovascular Center Hospital

Suita, 565-8565, Japan

Location

Mie University Hospital

Tsu, 514-8507, Japan

Location

University of Tsukuba Hospital

Tsukuba, 305-8576, Japan

Location

Yamagata University Hospital

Yamagata, 990-0828, Japan

Location

Yokohama City University Hospital

Yokohama, 236-0004, Japan

Location

Related Links

• A Prospective, Multicenter, Open-label, Single Arm, Phase III Study to Assess the Efficacy and Safety of Macitentan (ACT-064992) in Subjects With Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

MeSH Terms

Interventions

macitentan

Study Officials

• Yoshinari Yokoyama, PhD

  Actelion Japan

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2019
• First Posted: January 18, 2019
• Study Start: January 8, 2019
• Primary Completion: June 29, 2020
• Study Completion: June 29, 2020
• Last Updated: June 18, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

JP (23)