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

An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Patients With Exercise Induced Pulmonary Arterial Hypertension

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01338636

Acronym

EiPAH

Enrollment

Registered

2011-04-19

Start date

2008-09-30

Completion date

2016-05-31

Last updated

2022-01-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Exercise-induced Pulmonary Arterial Hypertension

Keywords

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

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.

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).

Interventions

DRUGAmbrisentan

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.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change From Baseline in Peak Exercise Maximum Oxygen Uptake (VO2max)	Baseline to Week 24	VO2max is the measurement of the maximum amount of oxygen that an individual can utilize during intense or maximal exercise.
Change From Baseline in Peak Exercise Pulmonary Vascular Resistance (PVR)	Baseline to Week 24	PVR is the resistance offered by the pulmonary circulatory system.
Change From Baseline in Peak Exercise Pulmonary Vascular Compliance (PVC )	Baseline to Week 24	PVC is a measure of a pulmonary vein's ability to expand.
Change From Baseline in Peak Exercise Cardiac Output (CO)	Baseline to Week 24	CO is the amount of blood pumped by the heart per minute.
Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP)	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.

Secondary

Measure	Time frame	Description
Borg Dyspnea Scale Score	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)
World Health Organization Functional Class (WHO FC)	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).
Change From Baseline in 6-minute Walk Distance (6MWD)	Baseline to Week 24	6MWD is the distance walked by the participant in 6 minutes.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Exercise-induced PAH 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.	30
Total	30

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	Withdrawn due to lack of improvement	8

Baseline characteristics

Characteristic	Exercise-induced PAH
Age, Continuous	60.12 years STANDARD_DEVIATION 9.17
Sex: Female, Male Female	19 Participants
Sex: Female, Male Male	11 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	25 / 30
serious Total, serious adverse events	0 / 30

Outcome results

Primary