- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01338636
An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH) (EiPAH)
An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Patients With Exercise Induced Pulmonary Arterial Hypertension
Study Overview
Status
Intervention / Treatment
Detailed Description
EIPAH population: These participants may provide a unique window into the pathogenesis of PAH. Our data suggest that these participants may represent an early phase of PAH with an abnormal vascular response.
The study includes an assessment of the potential impact of ambrisentan on the exercise capacity Advanced Level-3 cardiopulmonary exercise test (CPET) and the World Health Organization functional class (WHO FC).
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria
- 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.
- The participant has the presence, or history, of malignancy that required significant medical intervention within the preceding 3 months and/or is likely to result in death within the next 2 years.
- The participant has chronic renal impairment or renal insufficiency defined by a serum creatinine 2.5 mg/dL and/or the requirement for dialysis.
- The participant is lactating, breastfeeding, or pregnant.
- The participant received any chronic prostacyclin, prostacyclin analogue, ERA, or phosphodiesterase (PDE) inhibitor therapy within the 30 days prior to study entry. The use of PDE inhibitors "as needed" for erectile dysfunction is acceptable as long as the participant is not dosed within 24 hours of an efficacy assessment.
- The participant has a documented allergy to Lidocaine.
- Have received any investigational medication within 30 days prior to the start of this study or be scheduled to receive another investigational drug during the course of this study.
Study Plan
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 |
Intervention / Treatment |
---|---|
Other: Exercise-induced PAH
Open-label ambrisentan
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP)
Time Frame: Baseline to Week 24
|
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)
Time Frame: Baseline to Week 24
|
PVR is the resistance offered by the pulmonary circulatory system.
|
Baseline to Week 24
|
Change From Baseline in Peak Exercise Pulmonary Vascular Compliance (PVC )
Time Frame: Baseline to Week 24
|
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)
Time Frame: Baseline to Week 24
|
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)
Time Frame: Baseline to Week 24
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in 6-minute Walk Distance (6MWD)
Time Frame: Baseline to Week 24
|
6MWD is the distance walked by the participant in 6 minutes.
|
Baseline to Week 24
|
Borg Dyspnea Scale Score
Time Frame: Baseline and Week 24
|
The Borg Dyspnea Scale measures how breathless the participant feels.
Scores range from 0 (no shortness of breath) to 10 (more short of breath than ever experienced).
(minimum score 0, maximum score 10 with 10 being worsening outcome)
|
Baseline and Week 24
|
World Health Organization Functional Class (WHO FC)
Time Frame: Baseline and Week 24
|
The WHO FC categorizes cardiac disability using four classes, ranging from Class 1 (without limitation of physical activity) to Class 4 (inability to carry on any physical activity without discomfort).
|
Baseline and Week 24
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Aaron Waxman, MD, PhD, Brigham and Women's Hospital
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2008P000687
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
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.
Clinical Trials on Exercise-induced Pulmonary Arterial Hypertension
-
Brigham and Women's HospitalCompletedPulmonary Arterial Hypertension | Exercise Associated Pulmonary Arterial HypertensionUnited States
-
Laval UniversityUnknownPulmonary Arterial Hypertension | Exercise Training | Exercise Capacity | Muscle Function | Home-based Rehabilitation | Muscle Metabolism | Lipid Infiltration | Oxidative MetabolismCanada
-
Vanderbilt University Medical CenterJohns Hopkins UniversityCompletedPulmonary Arterial Hypertension | Idiopathic Pulmonary Arterial Hypertension | Associated Pulmonary Arterial Hypertension | Heritable Pulmonary Arterial HypertensionUnited States
-
American Medical Association FoundationWithdrawnIdiopathic Pulmonary Arterial Hypertension.United States
-
Vanderbilt University Medical CenterRecruitingIdiopathic Pulmonary Arterial Hypertension | Heritable Pulmonary Arterial Hypertension | Scleroderma Associated Pulmonary Arterial Hypertension | Appetite Suppressant Associate PAHUnited States
-
Amsterdam UMC, location VUmcZonMw: The Netherlands Organisation for Health Research and DevelopmentUnknown
-
Gachon University Gil Medical CenterChonbuk National University Hospital; Samsung Medical Center; Pusan National... and other collaboratorsUnknownPulmonary Arterial Hypertension | Idiopathic Pulmonary Arterial Hypertension | Deep Phenotyping | Heritable Pulmonary Arterial HypertensionKorea, Republic of
-
Association de Recherche en Physiopathologie RespiratoireGlaxoSmithKline; Soladis; InterlisUnknownPulmonary Arterial Hypertension (PAH)France
-
Medical University of GrazLudwig Boltzmann Institute for Lung Vascular ResearchCompletedIdiopathic Pulmonary Arterial HypertensionAustria
-
Zhejiang UniversityCompletedIdiopathic Pulmonary Arterial HypertensionChina
Clinical Trials on Ambrisentan
-
GlaxoSmithKlineTerminatedHypertension, PulmonaryFrance, United States, Germany, Spain, Italy, Japan, Hungary, Russian Federation, Argentina
-
GlaxoSmithKlineCompletedHypertension, PulmonaryFrance, Netherlands, Spain, Germany, Sweden, Australia, United Kingdom, Belgium, Canada, Italy, Greece, Slovakia, Norway, Czech Republic, Denmark
-
Medical University of GrazWithdrawn
-
Soumya ChatterjeeGilead SciencesCompleted
-
Gilead SciencesCompletedPulmonary Arterial HypertensionArgentina, Brazil, Chile, Mexico
-
Gilead SciencesCompletedStudy to Assess Safety and Efficacy of Ambrisentan in Subjects With Pulmonary Arterial Hypertension.Pulmonary Arterial Hypertension
-
University of Alabama at BirminghamCompletedPulmonary Arterial HypertensionUnited States
-
Gilead SciencesCompleted
-
GlaxoSmithKlineCompletedVascular DiseaseChina
-
Gilead SciencesCompleted