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

NCT05437224 | Completed Phase 3 DMC

• 1 other identifier: AMBEL
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Pulmonary Arterial Hypertension

Keywords

PAH; ambrisentan

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to 12 weeks and 24weeks in 6-minute Walk Distance

  The 6-minute walk test (6MWT) is a non-encouraged test, performed in a 30 m long flat corridor, where the patient is instructed to walk as far as possible, back and forth around two cones, with the permission to slow down, rest, or stop if needed. These guidelines were provided to all sites. For patients who had never performed a 6MWT previously, a training test was required before the qualifying tests for inclusion were performed.

  Baseline, week 12 and week 24

Secondary Outcomes (5)

• Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Clinical Worsening Events

  From Baseline to week 24

• Change from baseline to week 12 and 24 in Borg Dyspnea Index (BDI) sores

  Baseline, week 12 and week 24

• Number of participants with a change from baseline to week 12 and 24 in WHO functional class

  Baseline, week 12 and week 24

• Changes from baseline to week 12 and 24 in BNP plasma levels

  Baseline, week 12 and week 24

• Number and severity of Participants With Any Adverse Events

  From Baseline to week 24

Study Arms (1)

ambrisentan

EXPERIMENTAL

Open Label

Drug: Ambrisentan

Interventions

Ambrisentan 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.

ambrisentan

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• min walk test (6MWT), walking distance ≥ 50 m;
• Right heart catheterization performed within 6 months prior to screening and meeting the following hemodynamic criteria:
• mean pulmonary artery pressure ≥ 25 mm Hg；
• Pulmonary vascular resistance ≥ 240 dyn·s·cm-5;
• 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：
• Total lung capacity ≥ 60% of normal predicted value;
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• RenJi Hospital: lead
• Shanghai Zhongshan Hospital: collaborator
• The First Affiliated Hospital with Nanjing Medical University: collaborator
• Shanghai Pulmonary Hospital, Shanghai, China: collaborator
• Xinqiao Hospital of Chongqing: collaborator
• The Affiliated Hospital of Qingdao University: collaborator
• First Affiliated Hospital of Chongqing Medical University: collaborator
• Wuhan Asia Heart Hospital: collaborator

Study Sites (1)

Renji Hospital

Shanghai, 200127, China

Location

Related Publications (1)

• 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.

  PMID: 37378404 DERIVED

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Jieyan Shen, PhD

  Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: June 24, 2022
• First Posted: June 29, 2022
• Study Start: December 18, 2018
• Primary Completion: January 9, 2022
• Study Completion: February 6, 2022
• Last Updated: June 29, 2022

Record last verified: 2022-06

Locations

CN (1)