An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH)

NCT01338636 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2008P000687
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is assess whether ambrisentan can help people with exercise- induced pulmonary arterial hypertension (EIPAH). The investigators also want to find out if ambrisentan is safe to take without causing excessive side effects.

Conditions

Exercise-induced Pulmonary Arterial Hypertension

Keywords

Exercise-induced pulmonary arterial hypertension (EIPAH); Pulmonary arterial hypertension (PAH); ambrisentan; Advanced cardiopulmonary exercise test (CPET)

Outcome Measures

Primary Outcomes (5)

• Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP)

  mPAP is measure of the blood pressure found in the main artery of the lung. TPG is the difference between mean pulmonary arterial pressure and left atrial pressure. PCWP is the pressure measured by wedging a pulmonary catheter with an inflated balloon into a small pulmonary arterial branch.

  Baseline to Week 24

• Change From Baseline in Peak Exercise Pulmonary Vascular Resistance (PVR)

  PVR is the resistance offered by the pulmonary circulatory system.

  Baseline to Week 24

• Change From Baseline in Peak Exercise Pulmonary Vascular Compliance (PVC )

  PVC is a measure of a pulmonary vein's ability to expand.

  Baseline to Week 24

• Change From Baseline in Peak Exercise Cardiac Output (CO)

  CO is the amount of blood pumped by the heart per minute.

  Baseline to Week 24

• Change From Baseline in Peak Exercise Maximum Oxygen Uptake (VO2max)

  VO2max is the measurement of the maximum amount of oxygen that an individual can utilize during intense or maximal exercise.

  Baseline to Week 24

Secondary Outcomes (3)

• Change From Baseline in 6-minute Walk Distance (6MWD)

  Baseline to Week 24

• Borg Dyspnea Scale Score

  Baseline and Week 24

• World Health Organization Functional Class (WHO FC)

  Baseline and Week 24

Study Arms (1)

Exercise-induced PAH

OTHER

Open-label ambrisentan

Drug: Ambrisentan

Interventions

Ambrisentan DRUG

5 mg orally every day for 4 weeks. At Week 4, if ambrisentan 5 mg was tolerated, the dose was increased to 10 mg every day for the remainder of the 24-week period.

Also known as: Letairis

Exercise-induced PAH

Eligibility Criteria

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

You may qualify if:

• The participant provides written informed consent before the commencement of any study related procedure.
• The participant is 18 years of age or older.
• If a female participant of child-bearing potential, the participant must agree to use 2 forms of contraceptive therapy, including at least 1 barrier method, throughout the study and follow-up. (Women who are surgically sterile or those post-menopausal for at least 2 years are not considered to be of childbearing potential.)
• The participant has findings of either exercise induced PAH on an Advanced Level-3 CPET performed within the last 6-months and is a New York Heart Association (NYHA) Class I or II.
• The participant has a left ventricular ejection fraction (LVEF) of 55%, obtained by any appropriate method (i.e., echocardiographic assessment (ECHO), radionuclide imaging, or cardiac catheterization)
• The participant is taking a stable concomitant medication regimen for at least 4 weeks prior to enrollment in the study that is not expected to change during the study period and follow-up. Changes in diuretic and/or nitrate therapy as needed during the study period are acceptable.

You may not qualify if:

• The participant has clinically significant psychiatric, addictive, neurologic disease or any other condition that, in the Investigator's opinion, would compromise his/her ability to give informed consent, participate fully in this study, or prevent adherence to the requirements of the study protocol.
• The participant has evidence of unstable cardiovascular disease including intermittent atrial fibrillation or unstable angina within the 4 weeks prior to Screening.
• The participant has diagnosis of exercise induced heart failure with preserved ejection fraction (previously diastolic dysfunction).
• The participant has amyloidosis, hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, or constrictive pericarditis.
• The participant has a history of myocardial infarction, coronary artery bypass graft surgery, or percutaneous cardiac intervention within the last 3 months.
• The participant has clinically significant valvular heart disease in the opinion of the Investigator.
• The participant has a history of cerebrovascular accident or transient ischemic attack within the last 3 months.
• Participant has a serum alanine transaminase (ALT) or aspartate transaminase (AST) lab value that is greater than 1.5x upper limit of normal (ULN) prior to Baseline Visit.
• Participant has discontinued other endothelial receptor agonist (ERA) treatment (e.g. bosentan) for any adverse event.
• The participant has, in the opinion of the Investigator, a dependence on alcohol.
• The participant has, in the opinion of the Investigator, a dependence on illicit drugs.
• The participant has anemia defined as hemoglobin (Hgb) below 10.0 g/dL.
• A participant may qualify for the study following diagnosis and treatment of anemia, if the anemia is due to iron and/or vitamin deficiency.
• The participant has exercise tolerance limited by noncardiac causes (e.g., exercise-induced asthma, chronic obstructive pulmonary disease, malignancy, obesity, musculoskeletal disorder).
• The participant has uncontrolled systemic hypertension defined as a resting blood pressure of 140/90 mmHg if on no treatment for systemic hypertension or 160/90 mmHg if on 2 systemic hypertension medications. For participants who are receiving treatment for diabetes mellitus, uncontrolled systemic hypertension is defined as ≥ 130/80 mmHg.

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Gilead Sciences: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Interventions

ambrisentan

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Aaron B. Waxman
• Organization: Brigham and Women's Hospital Heart and Vascular Center

abwaxman@partners.org

617-525-9733

Study Officials

• Aaron Waxman, MD, PhD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Pulmonary Vascular Disease Program

Study Record Dates

• First Submitted: April 18, 2011
• First Posted: April 19, 2011
• Study Start: September 1, 2008
• Primary Completion: February 1, 2016
• Study Completion: May 1, 2016
• Last Updated: January 18, 2022
• Results First Posted: May 22, 2017

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)