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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Hypertension, Pulmonary

Treatments: Drug: tadalafil; Drug: ambrisentan

Study type: Interventional

Funder types: Industry

Identifiers

NCT01178073

112565

Details and patient eligibility

About

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.

Enrollment: 610 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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610 participants in 3 patient groups

Combination ambrisentan + tadalafil

Active Comparator group

Description:

ambrisentan + tadalafil

Treatment:

Drug: tadalafil

Drug: ambrisentan

Monotherapy ambrisentan

Active Comparator group

Description:

ambrisentan

Treatment:

Drug: ambrisentan

Monotherapy tadalafil

Active Comparator group

Description:

tadalafil

Treatment:

Drug: tadalafil