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

June 28, 2022 updated by: RenJi Hospital

A Multicenter Open Label Study to Evaluate Efficacy and Safety of China Made Ambrisentan in Chinese Patients With Pulmonary Arterial Hypertension

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China, 200127
        • Renji Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ambrisentan
Open Label
Drug: 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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline to 12 weeks and 24weeks in 6-minute Walk Distance
Time Frame: Baseline, week 12 and week 24
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) up to Week 24, Assessed as the First Occurrence of a Clinical Worsening Events
Time Frame: From Baseline to week 24
Clinical Worsening Events included a 15% decrease from baseline on the 6-minute walk test, hospitalization for pulmonary hypertension complications, dosing or escalation of pulmonary hypertension-targeted drugs, atrial septostomy, lung transplantation, or death. Time to clinical worsening of PAH is the time from baseline to the first clinical 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
Time Frame: Baseline, week 12 and week 24
The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum).
Baseline, week 12 and week 24
Number of participants with a change from baseline to week 12 and 24 in WHO functional class
Time Frame: Baseline, week 12 and week 24
The WHO FC was determined by the investigator as follows: Class I - Participants with pulmonary hypertension (PH) but without resulting limitation of physical activity; II- Participants with PH resulting in slight limitation of physical activity; III - Participants with PH resulting in marked limitation of physical activity; IV - Participants with PH with inability to carry out any physical activity without symptoms.
Baseline, week 12 and week 24
Changes from baseline to week 12 and 24 in BNP plasma levels
Time Frame: Baseline, week 12 and week 24
BNP is a surrogate maker of heart failure.
Baseline, week 12 and week 24
Number and severity of Participants With Any Adverse Events
Time Frame: From Baseline to week 24
An adverse event is defined as any adverse medical event in a patient that is not necessarily causally related to treatment. An adverse event can thus be any adverse or non-therapeutic sign (including abnormal laboratory results), symptom or disease temporally related to the use of the drug product, whether or not considered drug-related.
From Baseline to week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
RenJi Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
The First Affiliated Hospital with Nanjing Medical University
Shanghai Zhongshan Hospital
The Affiliated Hospital of Qingdao University
Shanghai Pulmonary Hospital, Shanghai, China
Xinqiao Hospital of Chongqing
Wuhan Asia Heart Hospital
First Affiliated Hospital of Chongqing Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 18, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 9, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 6, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 24, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 28, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 29, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 29, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 28, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AMBEL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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