Efficacy and Safety Study of Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension

• Status: Completed
• Trial end date: 2022-02-06
• Target enrollment: 0
• Participant gender: All

Summary

This multicenter, open label, single-arm study is aim at investigating the the efficacy and safety of china made ambrisentan in Chinese subjects with PAH.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: RenJi Hospital
• Collaborators: First Affiliated Hospital of Chongqing Medical University; Shanghai Pulmonary Hospital, Shanghai, China; Shanghai Zhongshan Hospital; The Affiliated Hospital of Qingdao University; The First Affiliated Hospital with Nanjing Medical University; Wuhan Asia Heart Hospital; Xinqiao Hospital of Chongqing
• Treatments: Ambrisentan

Criteria

Inclusion Criteria:

• Age ≥18 years old and ≤75 years old, regardless of gender;

• patients weighing ≥ 40 kg;

• Patients diagnosed with PAH in Group 1 of the WHO Updated Clinical Classification of Pulmonary Hypertension (WHO functional class II or III);

• 6 min walk test (6MWT), walking distance ≥ 50 m;

• Right heart catheterization performed within 6 months prior to screening and meeting the following hemodynamic criteria:

1. mean pulmonary artery pressure ≥ 25 mm Hg；

2. Pulmonary vascular resistance ≥ 240 dyn·s·cm-5;

3. Pulmonary artery wedge pressure or left ventricular end-diastolic pressure ≤ 15 mmHg;

• Subject receiving calcium channel blocker (CCB) drugs, only those whose doses have been stabilized for more than 4 weeks at the time of screening are allowed to be included in the study;

• Pulmonary function testing performed within 6 months prior to screening and meeting the following criteria：

1. Total lung capacity ≥ 60% of normal predicted value;

2. Forced expiratory volume in one second (FEV1) ≥ 55% of normal expected value;

• Female subjects of childbearing potential must have a negative pregnancy test at the Screening Visit and Day 0;

• Females subjects of childbearing potential must use a medically acceptable method of contraception (eg, hormone therapy, IUD, barrier methods such as condoms or cervical caps) during the study;

• Sign written informed consent

Exclusion Criteria:

• Patients diagnosed with WHO updated PH clinical classification of group 2, 3, 4, 5;

• Endothelin receptor antagonist therapy (eg, bosentan) has been discontinued prior to enrollment due to safety or tolerability concerns (non-drug-induced liver function abnormalities);

• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 2 times ULN;

• Serum bilirubin level > 1.5 times ULN;

• severe hepatic insufficiency (Child-Pugh class C);

• severe renal insufficiency (creatinine clearance <30 mL/min);

• Hemoglobin concentration < 10 g/dL or hematocrit < 30%;

• Contraindications to treatment identified by laboratory tests, physical examination, medical history, or other investigations

• severe hypotension (diastolic < 50 mm Hg or systolic < 90 mm Hg);

• Clinically significant aortic or mitral valve disease, pericardial constriction, restrictive or congestive cardiomyopathy, fatal arrhythmias, LV ejection fraction < 45%, LV outflow tract obstruction, symptomatic coronary heart disease, spontaneously low blood pressure;

• A history of malignancy within 5 years prior to enrollment, except for basal cell carcinoma of the skin and carcinoma in situ of the cervix;

• Subject taking endothelin receptor antagonists such as ambrisentan, bosentan and macitentan within 4 weeks prior to enrollment;

• pregnant and lactating women;

• Subject deemed unsuitable for participation in this study by other investigators