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

NCT ID: NCT05437224

Last Updated: 2022-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-18
• Study Completion Date: 2022-02-06

Brief 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.

Detailed Description

Pulmonary arterial hypertension is a hemodynamic and pathophysiological state, which can cause progressive hyperplasia of pulmonary vascular walls and elevated pulmonary arterial pressure for various reasons. Ambrisentan is a selective endothelin-A (ETA) receptor antagonist with vasodilatory, antiproliferative and vascular remodeling effects at a dose of 5 mg or 10 mg once daily, oral. A number of international clinical studies have shown that ambrisentan can improve the hemodynamic parameters, WHO functional classification and exercise tolerance of PAH patients, and improve the survival rate. The domestic Ambrisentan tablet is produced by Jiangsu Hansoh Pharmaceutical Group Co., Ltd. under the trade name of "Pu Nuo An". It has been developed and completed according to the consistency evaluation standard after the bioequivalence test, and is currently listed in mainland China. In view of the low price of the domestic ambrisentan, in order to verify its efficacy and safety in the real world, this post-marketing multicenter clinical study was carried out.

Conditions

Pulmonary Arterial Hypertension

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ambrisentan

Open Label

Group Type: EXPERIMENTAL

Ambrisentan

Intervention Type: DRUG

eligible subjects received 5 mg ambrisentan orally once daily for a 12-week primary evaluation period. Subjects then proceeded to a 12-week dose adjustment period during which dose titration to 10 mg was allowed.

Interventions

Ambrisentan

eligible subjects received 5 mg ambrisentan orally once daily for a 12-week primary evaluation period. Subjects then proceeded to a 12-week dose adjustment period during which dose titration to 10 mg was allowed.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: collaborator

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: collaborator

Shanghai Pulmonary Hospital, Shanghai, China

OTHER

Sponsor Role: collaborator

Xinqiao Hospital of Chongqing

OTHER

Sponsor Role: collaborator

The Affiliated Hospital of Qingdao University

OTHER

Sponsor Role: collaborator

First Affiliated Hospital of Chongqing Medical University

OTHER

Sponsor Role: collaborator

Wuhan Asia Heart Hospital

OTHER

Sponsor Role: collaborator

RenJi Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jieyan Shen, PhD

Role: STUDY_CHAIR

Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital

Locations

Renji Hospital

Shanghai, , China

Countries

China

References

Wang A, Chen M, Zhuang Q, Guan L, Xie W, Wang L, Huang W, Cheng Z, Yu S, Zhou H, Shen J. Time to clinical improvement: an appropriate surrogate endpoint for pulmonary arterial hypertension medication trials. Front Cardiovasc Med. 2023 Jun 12;10:1142721. doi: 10.3389/fcvm.2023.1142721. eCollection 2023.

Reference Type: DERIVED

PMID: 37378404 (View on PubMed)

Other Identifiers

AMBEL

Identifier Type: -

Identifier Source: org_study_id