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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: May 12, 2016
Last verified: May 2015
History of Changes
Results First Received: March 23, 2015  
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
Condition: Hypertension, Pulmonary
Interventions: Drug: ambrisentan
Drug: tadalafil

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
500 participants (par.) in the ITT Population were also included in the modified ITT Population (those who also met the modified inclusion/exclusion criteria defined in the protocol amendment 2). Disposition results below have been presented for the ITT Population.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 610 par. were randomized; however, only 605 were included in the Intent-to-Treat (ITT) Population (randomized par. who received at least one dose of IP). All par. received a minimum of 24 weeks of therapy unless they died or withdrew.

Reporting Groups
  Description
Combination Therapy: Ambrisentan + Tadalafil Participants initially received one tablet of 5 milligrams (mg) ambrisentan (AMB) and one tablet of AMB matching placebo once daily (QD) for the first 8 weeks plus one tablet of 20 mg tadalafil (TAD) and one tablet of TAD matching placebo QD for the first 4 weeks. The TAD dose was uptitrated to 40 mg (two tablets of 20 mg QD) after 4 weeks and the AMB dose may have been uptitrated to 10 mg (two tablets of 5 mg QD) after 8 weeks. The uptitration of AMB to 10 mg was not mandatory if the investigator decided for tolerability reasons the participants should remain on 5 mg.
Ambrisentan Monotherapy Participants initially received one tablet of 5 mg AMB and one tablet of AMB matching placebo QD for the first 8 weeks plus two tablets of TAD matching placebo. The AMB dose may have been uptitrated to 10 mg (two tablets of 5 mg QD) and two tablets of TAD matching placebo after 8 weeks. The uptitration of AMB to 10 mg was not mandatory if the investigator decided for tolerability reasons the participants should remain on 5 mg.
Tadalafil Monotherapy Participants initially received one tablet of 20 mg TAD and one tablet of TAD matching placebo QD for the first 4 weeks plus two tablets of AMB matching placebo. The TAD dose was uptitrated to 40 mg (two tablets of 20 mg QD) and two tablets of AMB matching placebo after 4 weeks.

Participant Flow:   Overall Study
    Combination Therapy: Ambrisentan + Tadalafil     Ambrisentan Monotherapy     Tadalafil Monotherapy  
STARTED     302     152     151  
COMPLETED     240     108     105  
NOT COMPLETED     62     44     46  
Adverse Event                 34                 27                 24  
Protocol Violation                 1                 1                 1  
Lost to Follow-up                 2                 0                 3  
Physician Decision                 14                 10                 10  
Withdrawal by Subject                 10                 6                 8  
Missing Completion Status                 1                 0                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Combination Therapy: Ambrisentan + Tadalafil Participants initially received one tablet of 5 milligrams (mg) ambrisentan (AMB) and one tablet of AMB matching placebo once daily (QD) for the first 8 weeks plus one tablet of 20 mg tadalafil (TAD) and one tablet of TAD matching placebo QD for the first 4 weeks. The TAD dose was uptitrated to 40 mg (two tablets of 20 mg QD) after 4 weeks and the AMB dose may have been uptitrated to 10 mg (two tablets of 5 mg QD) after 8 weeks. The uptitration of AMB to 10 mg was not mandatory if the investigator decided for tolerability reasons the participants should remain on 5 mg.
Ambrisentan Monotherapy Participants initially received one tablet of 5 mg AMB and one tablet of AMB matching placebo QD for the first 8 weeks plus two tablets of TAD matching placebo. The AMB dose may have been uptitrated to 10 mg (two tablets of 5 mg QD) and two tablets of TAD matching placebo after 8 weeks. The uptitration of AMB to 10 mg was not mandatory if the investigator decided for tolerability reasons the participants should remain on 5 mg.
Tadalafil Monotherapy Participants initially received one tablet of 20 mg TAD and one tablet of TAD matching placebo QD for the first 4 weeks plus two tablets of AMB matching placebo. The TAD dose was uptitrated to 40 mg (two tablets of 20 mg QD) and two tablets of AMB matching placebo after 4 weeks.
Total Total of all reporting groups

Baseline Measures
    Combination Therapy: Ambrisentan + Tadalafil     Ambrisentan Monotherapy     Tadalafil Monotherapy     Total  
Number of Participants  
[units: participants]
 		  302     152     151     605  
Age [1]
[units: Years]
Mean (Standard Deviation) 		  55.9  (13.86)     55.2  (14.41)     55.9  (14.75)     55.7  (14.21)  
Gender [1]
[units: Participants]
 		       
Female     223     117     121     461  
Male     79     35     30     144  
Race/Ethnicity, Customized [1]
[units: Participants]
 		       
African American/African Heritage     11     14     13     38  
American Indian or Alaskan Native     2     0     0     2  
Asian - Central/South Asian Heritage     1     2     1     4  
Asian - Japanese Heritage     3     0     1     4  
Asian - South East Asian Heritage     1     2     1     4  
Native Hawaiian or Other Pacific Islander     1     0     2     3  
White - Arabic /North African Heritage     1     1     0     2  
White - White/Caucasian/European Heritage     280     131     133     544  
Mixed Race     2     1     0     3  
Missing     0     1     0     1  
[1] Intent-to-Treat Population



  Outcome Measures
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1.  Primary:   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) ]
  Show Outcome Measure 1

2.  Secondary:   Percent Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Week 24   [ Time Frame: Baseline and Week 24 ]
  Show Outcome Measure 2

3.  Secondary:   Percentage of Participants With a Satisfactory Clinical Response at Week 24   [ Time Frame: Baseline and Week 24 ]
  Show Outcome Measure 3

4.  Secondary:   Change From Baseline in the 6 Minute Walk Distance Test at Week 24   [ Time Frame: Baseline and Week 24 ]
  Show Outcome Measure 4

5.  Secondary:   Change From Baseline in the World Health Organization Functional Class at Week 24   [ Time Frame: Baseline and Week 24 ]
  Show Outcome Measure 5

6.  Secondary:   Change From Baseline in Borg Dyspnea Index at Week 24   [ Time Frame: Baseline (BL) and Week 24 ]
  Show Outcome Measure 6


  Serious Adverse Events
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  Other Adverse Events
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  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):


Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01178073     History of Changes
Other Study ID Numbers: 112565
Study First Received: July 15, 2010
Results First Received: March 23, 2015
Last Updated: May 12, 2016
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