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

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT01178073
• Date of registration: 15/07/2010
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH) AMBITION
• Scientific title: AMBITION: A Randomised, Multicenter Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
• Date of first enrolment: October 1, 2010
• Target sample size: 610
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01178073
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Australia, Austria, Belgium, Canada, France, Germany, Greece, Italy, Japan, Netherlands, Spain, Sweden, United Kingdom, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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 <500 dyne/sec/cm5 , or PCWP/LVEDP = 15 mmHg if PVR =500 dynes/sec/cm5

- Subject must walk a distance of =125m and =500m at the screening visit

Exclusion Criteria:

- Subject received previous PAH therapy (phosphodiesterase type 5 inhibitor (PDE5i),
endothelin receptor antagonist (ERA), chronic prostanoid*) within 4 weeks prior to the
screening visit (*Chronic prostanoid use is considered >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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hypertension, Pulmonary

Intervention(s)

Drug: tadalafil

Drug: ambrisentan

Primary Outcome(s)

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 [Time Frame: From Baseline up to the Final Assessment Visit (FAV) (average of 609 days)]

Secondary Outcome(s)

Percentage of Participants With a Satisfactory Clinical Response at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in Borg Dyspnea Index at Week 24 [Time Frame: Baseline (BL) and Week 24]

Percent Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in the World Health Organization Functional Class at Week 24 [Time Frame: Baseline and Week 24]

Change From Baseline in the 6 Minute Walk Distance Test at Week 24 [Time Frame: Baseline and Week 24]

Secondary ID(s)

112565

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Gilead Sciences

Results

• Results available: Yes
• Date Posted: 28/04/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01178073