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: October 23, 2014
Last verified: October 2014

July 15, 2010
October 23, 2014
October 2010
April 2014   (final data collection date for primary outcome measure)
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 ]
Time to Clinical Failure [ Time Frame: The study will be terminated when it is projected that approximately 82 events have occurred. Based on current assumptions, the median treatment duration is anticipated to be 1.6 years with the total study duration estimated at 2.5 years. ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01178073 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 6 minute Walk Distance test [ Time Frame: Change from baseline to Week 24 ] [ Designated as safety issue: No ]
  • Percentage of subjects with unsatisfactory clinical response [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  • N-terminal pro-B-type natriuretic peptide (NT-Pro BNP) [ Time Frame: Change from baseline to Week 24 ] [ Designated as safety issue: No ]
  • World Health Organisation (WHO) Functional Class [ Time Frame: Change from baseline to Week 24 ] [ Designated as safety issue: No ]
  • Borg Dyspnea Index [ Time Frame: Change from baseline to Week 24 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
AMBITION: A Randomised, Multicenter Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Hypertension, Pulmonary
  • Drug: ambrisentan
    ambrisentan (target dose: 10mg)
  • Drug: tadalafil
    tadalafil (target dose: 40mg)
  • Active Comparator: Combination ambrisentan + tadalafil
    ambrisentan + tadalafil
    Interventions:
    • Drug: ambrisentan
    • Drug: tadalafil
  • Active Comparator: Monotherapy ambrisentan
    ambrisentan
    Intervention: Drug: ambrisentan
  • Active Comparator: Monotherapy tadalafil
    tadalafil
    Intervention: Drug: tadalafil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
610
August 2014
April 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Germany,   United States,   Australia,   Austria,   Belgium,   Canada,   France,   United Kingdom,   Greece,   Italy,   Japan,   Netherlands,   Spain,   Sweden
 
NCT01178073
112565
Yes
GlaxoSmithKline
GlaxoSmithKline
Gilead Sciences
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
October 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP