Last updated: 11/03/2018 13:03:55
A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects with Pulmonary Arterial Hypertension (PAH)AMBITION
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: AMBITION: A Randomised, Multicenter Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects with Pulmonary Arterial Hypertension (PAH)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
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
Timeframe: From Baseline up to the Final Assessment Visit (FAV) (average of 609 days)
Secondary outcomes:
Percent change from Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Week 24
Timeframe: Baseline and Week 24
Percentage of participants with a satisfactory clinical response at Week 24
Timeframe: Baseline and Week 24
Change from Baseline in the 6 minute walk distance test at Week 24
Timeframe: Baseline and Week 24
Change from Baseline in the World Health Organization Functional Class at Week 24
Timeframe: Baseline and Week 24
Change from Baseline in Borg Dyspnea Index at Week 24
Timeframe: Baseline (BL) and Week 24
Interventions:
Drug: ambrisentan
Drug: tadalafil
Enrollment:
610
Observational study model:
Not applicable
Primary completion date:
2014-31-07
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Hypertension, Pulmonary
Product
ambrisentan
Collaborators
Gilead Sciences
Study date(s)
October 2010 to July 2014
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18 - 75 years
Accepts healthy volunteers
No
- Subjects must have a diagnosis of Pulmonary Arterial Hypertension (PAH) due to the following:
- a. idiopathic or heritable PAH
- 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
Inclusion and 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.
Trial location(s)
Location
GSK Investigational Site
New Orleans, Louisiana, United States, 70112
Status
Study Complete
Location
GSK Investigational Site
Gainesville, Florida, United States, 32610
Status
Study Complete
Location
GSK Investigational Site
Decatur, Georgia, United States, 30030
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Ann Arbor, Michigan, United States, 48109
Status
Study Complete
Location
GSK Investigational Site
Atlanta, Georgia, United States, 30322
Status
Study Complete
Location
GSK Investigational Site
Milwaukee, Wisconsin, United States, 53215
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10003
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Greifswald, Mecklenburg-Vorpommern, Germany, 17475
Status
Study Complete
Location
GSK Investigational Site
Sacramento, California, United States, 95817
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19140
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Newark, New Jersey, United States, 07112
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63110
Status
Study Complete
Location
GSK Investigational Site
L'Hospitalet de Llobregat, Spain, 08907
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10032
Status
Study Complete
Location
GSK Investigational Site
Aurora, Colorado, United States, 80045
Status
Study Complete
Location
GSK Investigational Site
Baltimore, Maryland, United States, 21201
Status
Study Complete
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Status
Study Complete
Location
GSK Investigational Site
Kissimmee, Florida, United States, 34741
Status
Study Complete
Location
GSK Investigational Site
Oakbrook Terrace, Illinois, United States, 60181
Status
Study Complete
Location
GSK Investigational Site
Morristown, New Jersey, United States, 07962
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Norfolk, Virginia, United States, 23507
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Camperdown, New South Wales, Australia, 2050
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02115
Status
Study Complete
Location
GSK Investigational Site
Detroit, Michigan, United States, 48201
Status
Study Complete
Location
GSK Investigational Site
Kansas City, Kansas, United States, 66160
Status
Study Complete
Location
GSK Investigational Site
Vancouver, British Columbia, Canada, V5Z 1M9
Status
Study Complete
Location
GSK Investigational Site
Rochester, New York, United States, 14623
Status
Study Complete
Location
GSK Investigational Site
La Jolla, California, United States, 92093
Status
Study Complete
Location
GSK Investigational Site
Torrance, California, United States, 90502
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02118
Status
Study Complete
Location
GSK Investigational Site
Loewenstein, Baden-Wuerttemberg, Germany, 74245
Status
Study Complete
Location
GSK Investigational Site
Chermside, Queensland, Australia, 4032
Status
Study Complete
Location
GSK Investigational Site
Melbourne, Victoria, Australia, 3004
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Jacksonville, Florida, United States, 32209
Status
Study Complete
Location
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27599
Status
Study Complete
Location
GSK Investigational Site
Phoenix, Arizona, United States, 85012
Status
Study Complete
Location
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15212
Status
Study Complete
Location
GSK Investigational Site
Bonn, Nordrhein-Westfalen, Germany, 53127
Status
Study Complete
Location
GSK Investigational Site
Richmond, Virginia, United States, 23298
Status
Study Complete
Location
GSK Investigational Site
Freiburg, Baden-Wuerttemberg, Germany, 79106
Status
Study Complete
Location
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
Status
Study Complete
Location
GSK Investigational Site
Perth, Western Australia, Australia, 6000
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Asheville, North Carolina, United States, 28803
Status
Study Complete
Location
GSK Investigational Site
Le Kremlin-Bicêtre cedex, France, 94275
Status
Study Complete
Location
GSK Investigational Site
Darlinghurst, New South Wales, Australia, 2010
Status
Study Complete
Location
GSK Investigational Site
Birmingham, Alabama, United States, 35294
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10021
Status
Study Complete
Location
GSK Investigational Site
Cambridge, Cambridgeshire, United Kingdom, CB3 8RE
Status
Study Complete
Location
GSK Investigational Site
Charlottesville, Virginia, United States, 22908
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Hobart, Tasmania, Australia, 7000
Status
Terminated/Withdrawn
Location
GSK Investigational Site
Los Angeles, California, United States, 90073
Status
Study Complete
Location
GSK Investigational Site
Providence, Rhode Island, United States, 02903
Status
Study Complete
Location
GSK Investigational Site
Orlando, Florida, United States, 32803
Status
Study Complete
Location
GSK Investigational Site
Springfield, Massachusetts, United States, 01199
Status
Study Complete
Location
GSK Investigational Site
Portland, Oregon, United States, 97220
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45267
Status
Study Complete
Location
GSK Investigational Site
New York, New York, United States, 10019
Status
Study Complete
Location
GSK Investigational Site
Cincinnati, Ohio, United States, 45219
Status
Study Complete
Location
GSK Investigational Site
Heidelberg, Baden-Wuerttemberg, Germany, 69126
Status
Study Complete
Location
GSK Investigational Site
MAASTRICHT, Netherlands, 6229 HX
Status
Terminated/Withdrawn
Location
GSK Investigational Site
New Hyde Park, New York, United States, 11040
Status
Study Complete
Location
GSK Investigational Site
Boston, Massachusetts, United States, 02111
Status
Study Complete
Location
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
Status
Study Complete
Location
GSK Investigational Site
Philadelphia, Pennsylvania, United States, 19104
Status
Study Complete
Location
GSK Investigational Site
Nashville, Tennessee, United States, 37232
Status
Study Complete
Study documents
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2014-31-07
Actual study completion date
2014-31-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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Access to clinical trial data by researchers
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