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

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.

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).

Eligibility 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.