Phase 3 Completed N=605 Randomized Quadruple-blind Treatment

A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)

Hypertension, Pulmonary

Source: ClinicalTrials.gov NCT01178073 ↗

Enrolled (actual)

605

Serious AEs

42.2%

Results posted

Apr 2015

Primary outcomePrimary: Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV — 46; 77; 43; 34 Participants — p=0.0002

Summary

The purpose of this study is to compare the two treatment strategies; first-line combination therapy (ambrisentan and tadalafil) versus first-line monotherapy (ambrisentan or tadalafil) in subjects with Pulmonary Arterial Hypertension. This will be assessed by time to the first clinical failure event.

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With First Adjudicated Clinical Failure (CF) Event, Death, Hospitalisation for Worsening PAH, Disease Progression, Unsatisfactory Long-term Clinical Response, All Through FAV	46; 77; 43; 34; 9; 8	0.0002 sig
SECONDARY Percent Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Week 24	-67.15; -50.37; -56.15; -43.83	<0.0001 sig
SECONDARY Percentage of Participants With a Satisfactory Clinical Response at Week 24	39; 29; 31; 27	0.0264 sig
SECONDARY Change From Baseline in the 6 Minute Walk Distance Test at Week 24	48.98; 23.80; 27.00; 22.70	<0.0001 sig
SECONDARY Change From Baseline in the World Health Organization Functional Class at Week 24	0.0; 0.0; 0.0; 0.0	0.2287
SECONDARY Change From Baseline in Borg Dyspnea Index at Week 24	-1.00; -0.50; -0.50; -0.50	—

Eligibility Criteria

Inclusion Criteria

Subjects must have a diagnosis of Pulmonary Arterial Hypertension (PAH) due to the following:

a. idiopathic or heritable PAH b. PAH associated with: i. connective tissue disease (e.g., limited scleroderma, diffuse scleroderma, mixed connective tissue disease, systemic lupus erythematosus, or overlap syndrome) ii. drugs or toxins iii. Human Immunodeficiency Virus (HIV) infection iv. congenital heart defects repaired greater than 1 year prior to screening (i.e., atrial septal defects, ventricular septal defects, and patent ductus arteriosus) NB: subjects with portopulmonary hypertension and pulmonary veno-occlusive disease are NOT eligible for the study

Subject must have a current diagnosis of being in World Health Organisation (WHO) Functional Class II or III.
Subject must meet all of the following haemodynamic criteria by means of a right heart catheterization prior to screening:

i. mPAP of ≥25 mmHg ii. PVR ≥ 300 dynes/sec/cm5 iii. PCWP or LVEDP of ≤12 mmHg if PVR ≥300 to 7 days of treatment)

Subject received ERA treatment (e.g., bosentan or sitaxentan) or PDE5i treatment (e.g. Sildenafil) at any time AND discontinued due to tolerance issues other than those associated with liver function abnormalities
Subjects who have previously discontinued ambrisentan or tadalafil in either another clinical study or commercial product (Volibris/Letairis or Adcirca) for safety or tolerability reasons.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01178073). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.