Trial Outcomes & Findings for An Open-Label Uncontrolled Study of the Safety and Efficacy of Ambrisentan in Participants With Exercise-Induced Pulmonary Arterial Hypertension (PAH) (NCT NCT01338636)

NCT ID: NCT01338636

Last Updated: 2022-01-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 30 participants
• Primary outcome timeframe: Baseline to Week 24
• Results posted on: 2022-01-18

Participant Flow

Participant milestones

Measure	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.
Overall Study STARTED	30
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	8

Reasons for withdrawal

Measure	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.
Overall Study Withdrawn due to lack of improvement	8

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Exercise-induced PAH n=30 Participants 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.
Age, Continuous	60.12 years STANDARD_DEVIATION 9.17 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: The analysis population included evaluable participants who completed the 24-week treatment period.

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.

Outcome measures

Measure	Exercise-induced PAH n=22 Participants 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.
Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP) mPAP	-5.2 mmHg Standard Deviation 5.6
Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP) TPG	-7.1 mmHg Standard Deviation 8.0
Changes From Baseline in Peak Exercise Mean Pulmonary Artery Pressure (mPAP), Transpulmonary Pressure Gradient (TPG), and Pulmonary Capillary Wedge Pressure (PCWP) PCWP	2.9 mmHg Standard Deviation 5.6

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: The analysis population included evaluable participants who completed the 24-week treatment period.

PVR is the resistance offered by the pulmonary circulatory system.

Outcome measures

Measure	Exercise-induced PAH n=22 Participants 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.
Change From Baseline in Peak Exercise Pulmonary Vascular Resistance (PVR)	-0.9 Woods units (WU) Standard Deviation 0.7

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: The analysis population included evaluable participants who completed the 24-week treatment period.

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

Outcome measures

Measure	Exercise-induced PAH n=22 Participants 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.
Change From Baseline in Peak Exercise Pulmonary Vascular Compliance (PVC )	0.8 mL/mmHg Standard Deviation 1.4

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: The analysis population included evaluable participants who completed the 24-week treatment period.

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

Outcome measures

Measure	Exercise-induced PAH n=22 Participants 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.
Change From Baseline in Peak Exercise Cardiac Output (CO)	2.3 L/min Standard Deviation 1.4

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: The analysis population included evaluable participants who completed the 24-week treatment period.

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

Outcome measures

Measure	Exercise-induced PAH n=22 Participants 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.
Change From Baseline in Peak Exercise Maximum Oxygen Uptake (VO2max)	4.4 percent predicted Standard Deviation 2.6

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: The analysis population included evaluable participants who completed the 24-week treatment period.

6MWD is the distance walked by the participant in 6 minutes.

Outcome measures

Measure	Exercise-induced PAH n=22 Participants 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.
Change From Baseline in 6-minute Walk Distance (6MWD)	34.8 meters Standard Deviation 73.2

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: The analysis population included evaluable participants who completed the 24-week treatment period.

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)

Outcome measures

Measure	Exercise-induced PAH n=22 Participants 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.
Borg Dyspnea Scale Score Baseline	5.1 score on a scale Standard Deviation 2.8
Borg Dyspnea Scale Score Week 24	3.0 score on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: The analysis population included evaluable participants who completed the 24-week treatment period.

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).

Outcome measures

Measure	Exercise-induced PAH n=22 Participants 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.
World Health Organization Functional Class (WHO FC) Baseline	2.0 class Standard Deviation 0.6
World Health Organization Functional Class (WHO FC) Week 24	1.5 class Standard Deviation 0.6

Adverse Events

Exercise-induced PAH

Serious events: 0 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Exercise-induced PAH n=30 participants at risk 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.
Metabolism and nutrition disorders Peripheral edema	23.3% 7/30 • 24 weeks
Respiratory, thoracic and mediastinal disorders Nasal congestion	23.3% 7/30 • 24 weeks
Nervous system disorders Headache	16.7% 5/30 • 24 weeks
Vascular disorders Flushing	13.3% 4/30 • 24 weeks
Respiratory, thoracic and mediastinal disorders Increased cough	13.3% 4/30 • 24 weeks
Musculoskeletal and connective tissue disorders Joint and body pain	10.0% 3/30 • 24 weeks
Skin and subcutaneous tissue disorders Rash	6.7% 2/30 • 24 weeks
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	6.7% 2/30 • 24 weeks
Gastrointestinal disorders Gastrointestinal infection	6.7% 2/30 • 24 weeks
Musculoskeletal and connective tissue disorders Jaw pain	3.3% 1/30 • 24 weeks
Vascular disorders Nose bleed	3.3% 1/30 • 24 weeks
Cardiac disorders Palpitations	3.3% 1/30 • 24 weeks
Nervous system disorders Dizziness	3.3% 1/30 • 24 weeks
Cardiac disorders Worsening dyspnea on exertion	26.7% 8/30 • 24 weeks

Additional Information

Aaron B. Waxman

Brigham and Women's Hospital Heart and Vascular Center

Phone: 617-525-9733

Email: abwaxman@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place