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

This study has been completed.
Sponsor:
Collaborator:
Gilead Sciences
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01178073
First received: July 15, 2010
Last updated: November 20, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Hypertension, Pulmonary
Drug: ambrisentan
Drug: tadalafil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: AMBITION: A Randomised, Multicenter Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Time to Clinical Failure [ Time Frame: The study will be terminated when it is projected that approximately 105 events have occurred. Based on current assumptions, the median treatment duration is anticipated to be 2.25 years with the total study duration estimated at 3.5 years. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from baseline in 6 minute Walk Distance test [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Percentage of subjects with unsatisfactory clinical response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in World Health Organisation (WHO) Functional Class [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in Borg Dyspnea Index [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Enrollment: 610
Study Start Date: October 2010
Study Completion Date: August 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Combination ambrisentan + tadalafil
ambrisentan + tadalafil
Drug: ambrisentan
ambrisentan (target dose: 10mg)
Drug: tadalafil
tadalafil (target dose: 40mg)
Active Comparator: Monotherapy ambrisentan
ambrisentan
Drug: ambrisentan
ambrisentan (target dose: 10mg)
Active Comparator: Monotherapy tadalafil
tadalafil
Drug: tadalafil
tadalafil (target dose: 40mg)

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01178073

  Show 143 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Gilead Sciences
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01178073     History of Changes
Other Study ID Numbers: 112565
Study First Received: July 15, 2010
Last Updated: November 20, 2014
Health Authority: Spain: Agencia Española del Medicamento y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Austria: Agency for Health and Food Safety
Belgium: Agence Fédérale des Médicaments et des Produits de la Santé
Italy: Comitato Etico Indipendente
Canada: Health Canada
Germany: Bundesinstitut für Arzneimittel und Medizinprodukte
France: Agence Française de Sécurité Sanitaire des Produits de Santé
Japan: Pharmaceuticals and Medical Devices Agency
Netherlands: De Centrale Commissie Mensgebonden Onderzoek
United States: Food and Drug Administration
Sweden: Läkemedelsverket
Australia: Therapeutic Goods Administration
Greece: National Drug Organisation

Keywords provided by GlaxoSmithKline:
Ambrisentan
Sponsor US: Gilead
Tadalafil
Sponsor Rest of World: GSK
PAH
Pulmonary Arterial Hypertension

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Tadalafil
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on November 27, 2014