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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01338636
• Date of registration: 18/04/2011
• Prospective Registration: No
• Primary sponsor: Brigham and Women's Hospital
• Public title: An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH) EiPAH
• Scientific title: An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Patients With Exercise Induced Pulmonary Arterial Hypertension
• Date of first enrolment: September 2008
• Target sample size: 30
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01338636
• Study type: Interventional
• Study design: Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

United States

Contacts

• Name: Aaron Waxman, MD, PhD
• Affiliation: Brigham and Women's Hospital

Key inclusion & exclusion criteria

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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Exercise-induced Pulmonary Arterial Hypertension

Intervention(s)

Drug: Ambrisentan

Primary Outcome(s)

Change From Baseline in Peak Exercise Pulmonary Vascular Compliance (PVC ) [Time Frame: Baseline to Week 24]

Change From Baseline in Peak Exercise Pulmonary Vascular Resistance (PVR) [Time Frame: Baseline to Week 24]

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]

Change From Baseline in Peak Exercise Maximum Oxygen Uptake (VO2max) [Time Frame: Baseline to Week 24]

Change From Baseline in Peak Exercise Cardiac Output (CO) [Time Frame: Baseline to Week 24]

Secondary Outcome(s)

Borg Dyspnea Scale Score [Time Frame: Baseline and Week 24]

Change From Baseline in 6-minute Walk Distance (6MWD) [Time Frame: Baseline to Week 24]

World Health Organization Functional Class (WHO FC) [Time Frame: Baseline and Week 24]

Secondary ID(s)

2008P000687

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Gilead Sciences

Results

• Results available: Yes
• Date Posted: 22/05/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01338636