search
Back to results

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

Primary Purpose

Hypertension, Pulmonary

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ambrisentan
tadalafil
Sponsored by
GlaxoSmithKline
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension, Pulmonary focused on measuring Pulmonary Arterial Hypertension, Ambrisentan, Sponsor Rest of World: GSK, Tadalafil, PAH, Sponsor US: Gilead

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site
  • GSK Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Combination ambrisentan + tadalafil

Monotherapy ambrisentan

Monotherapy tadalafil

Arm Description

ambrisentan + tadalafil

ambrisentan

tadalafil

Outcomes

Primary Outcome Measures

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 to the first adjudicated CF event (death, hospitalization for worsening pulmonary arterial hypertension [PAH], disease progression, or unsatisfactory long-term clinical response) after initiating either first-line combination therapy with AMB and TAD or first-line monotherapy with either drug (AMB or TAD) in par. with PAH was assessed. If data was not available for some par. following a loss to follow-up, their event times were treated as censored at their last assessment time for the statistical analyses. FAV occurred approximately 4 weeks after the predicted 105th adjudicated first CF event was reached. Par. who had an FAV, and who had no adjudicated events or whose first adjudicated event occurred after their FAV, were censored at their individual FAV. Modified Intent-to-Treat (mITT) Population: all randomized par. who met the PAH diagnosis and inclusion/exclusion criteria defined in protocol amendment 2 and who also received at least one dose of investigational product (IP).

Secondary Outcome Measures

Percent Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Week 24
N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) is a surrogate marker of heart failure. The data were log-transformed. The geometric mean was calculated (based on the log-transformed data). The geometric mean ratio was calculated as the ratio between the Week 24 value and the Baseline value (based on the log-transformed data) and presented as percent change = 100 * (geometric mean ratio - 1). The Baseline value is the last value prior to administration of study drug; this may be prior to or on the day of study drug initiation. No imputation was performed for missing data. The secondary endpoints were analyzed according to a pre-specified hierarchical testing procedure.
Percentage of Participants With a Satisfactory Clinical Response at Week 24
A satisfactory clinical response at Week 24 is defined as a participant who meets all of the following criteria: 10% improvement in 6MWD compared with Baseline; improvement to or maintenance of World Health Organization (WHO) class I or II symptoms; no events of clinical worsening prior to or at the Week 24 visit. Clinical worsening events included: death, hospitalization for pulmonary arterial hypertension (PAH), and disease progression. Participants without an event of clinical worsening prior to or at the Week 24 visit who did not have a 6MWD value or a WHO functional class value at Week 24 were excluded from the analysis.
Change From Baseline in the 6 Minute Walk Distance Test at Week 24
The 6-minute walk distance (6MWD) test measures the distance that a participant can walk in a period of 6 minutes. Change from Baseline was calculated as the Week 24 value minus the Baseline value. The analysis was performed based on last observation carried forward data, except in the case of an adjudicated clinical failure event of death or hospitalization preceding the missing data observation. In this case, the missing observation was assigned the worst-rank score relative to those actually observed and was assigned a rank reflecting the relative order of the actual event times. Baseline 6MWD comprised of an average of the last two consecutive measurements prior to randomization that varied by no greater than 10%. If only one measurement was available, that measurement was used. If no two consecutive measures vary by no greater than 10% then Baseline was based on the last two consecutive measures for a participant.
Change From Baseline in the World Health Organization Functional Class at Week 24
The WHO Functional Class (FC) indicates the severity of PAH and is an adaptation of the New York Heart Association classification. It was assessed by the investigator. There are four grades for WHO FC based on severity of symptoms (Class I = none, Class IV = most severe). Baseline WHO FC is the latest assessment prior to dosing (i.e., at Randomization or Screening). Change from Baseline at Week 24 was calculated as the Week 24 value minus the Baseline value. The analysis was performed based on the last observation carried forward data, except in the case of an adjudicated clinical failure event of death or hospitalization preceding the missing data observation. In this case, the missing observations was assigned the worst-rank score relative to those actually observed and was assigned rank reflecting the relative order of the actual event times.
Change From Baseline in Borg Dyspnea Index at Week 24
Borg Dyspnea Index (BDI) indicates the degree of breathlessness after completion of the 6 minute walk test. The BDI was calculated by using the Borg category (C) ratio (R) CR10 scale which starts at 0 (nothing at all) and has no upper limit (extremely strong). Change from BL was calculated as the Week 24 values minus the BL value. The BDI scale was assessed by each participant. The BL BDI score is the average of the two BDI values obtained following the two 6MWD tests used in determining the BL 6MWD. A negative change from BL in the BDI score represented an improvement for the participant. The analysis was performed based on the last observation carried forward data, except in the case of an adjudicated clinical failure event of death or hospitalization preceding the missing data observation. In this case, the missing observation was assigned the worst-rank score relative to those actually observed and was assigned rank reflecting the relative order of the actual event times.

Full Information

First Posted
July 15, 2010
Last Updated
August 14, 2017
Sponsor
GlaxoSmithKline
Collaborators
Gilead Sciences
search

1. Study Identification

Unique Protocol Identification Number
NCT01178073
Brief Title
A Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
Acronym
AMBITION
Official Title
AMBITION: A Randomised, Multicenter Study of First-Line Ambrisentan and Tadalafil Combination Therapy in Subjects With Pulmonary Arterial Hypertension (PAH)
Study Type
Interventional

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
October 1, 2010 (undefined)
Primary Completion Date
July 31, 2014 (Actual)
Study Completion Date
July 31, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
Collaborators
Gilead Sciences

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Pulmonary
Keywords
Pulmonary Arterial Hypertension, Ambrisentan, Sponsor Rest of World: GSK, Tadalafil, PAH, Sponsor US: Gilead

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
610 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Combination ambrisentan + tadalafil
Arm Type
Active Comparator
Arm Description
ambrisentan + tadalafil
Arm Title
Monotherapy ambrisentan
Arm Type
Active Comparator
Arm Description
ambrisentan
Arm Title
Monotherapy tadalafil
Arm Type
Active Comparator
Arm Description
tadalafil
Intervention Type
Drug
Intervention Name(s)
ambrisentan
Intervention Description
ambrisentan (target dose: 10mg)
Intervention Type
Drug
Intervention Name(s)
tadalafil
Intervention Description
tadalafil (target dose: 40mg)
Primary Outcome Measure Information:
Title
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
Description
Time to the first adjudicated CF event (death, hospitalization for worsening pulmonary arterial hypertension [PAH], disease progression, or unsatisfactory long-term clinical response) after initiating either first-line combination therapy with AMB and TAD or first-line monotherapy with either drug (AMB or TAD) in par. with PAH was assessed. If data was not available for some par. following a loss to follow-up, their event times were treated as censored at their last assessment time for the statistical analyses. FAV occurred approximately 4 weeks after the predicted 105th adjudicated first CF event was reached. Par. who had an FAV, and who had no adjudicated events or whose first adjudicated event occurred after their FAV, were censored at their individual FAV. Modified Intent-to-Treat (mITT) Population: all randomized par. who met the PAH diagnosis and inclusion/exclusion criteria defined in protocol amendment 2 and who also received at least one dose of investigational product (IP).
Time Frame
From Baseline up to the Final Assessment Visit (FAV) (average of 609 days)
Secondary Outcome Measure Information:
Title
Percent Change From Baseline in the N-Terminal Pro-B-Type Natriuretic Peptide at Week 24
Description
N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) is a surrogate marker of heart failure. The data were log-transformed. The geometric mean was calculated (based on the log-transformed data). The geometric mean ratio was calculated as the ratio between the Week 24 value and the Baseline value (based on the log-transformed data) and presented as percent change = 100 * (geometric mean ratio - 1). The Baseline value is the last value prior to administration of study drug; this may be prior to or on the day of study drug initiation. No imputation was performed for missing data. The secondary endpoints were analyzed according to a pre-specified hierarchical testing procedure.
Time Frame
Baseline and Week 24
Title
Percentage of Participants With a Satisfactory Clinical Response at Week 24
Description
A satisfactory clinical response at Week 24 is defined as a participant who meets all of the following criteria: 10% improvement in 6MWD compared with Baseline; improvement to or maintenance of World Health Organization (WHO) class I or II symptoms; no events of clinical worsening prior to or at the Week 24 visit. Clinical worsening events included: death, hospitalization for pulmonary arterial hypertension (PAH), and disease progression. Participants without an event of clinical worsening prior to or at the Week 24 visit who did not have a 6MWD value or a WHO functional class value at Week 24 were excluded from the analysis.
Time Frame
Baseline and Week 24
Title
Change From Baseline in the 6 Minute Walk Distance Test at Week 24
Description
The 6-minute walk distance (6MWD) test measures the distance that a participant can walk in a period of 6 minutes. Change from Baseline was calculated as the Week 24 value minus the Baseline value. The analysis was performed based on last observation carried forward data, except in the case of an adjudicated clinical failure event of death or hospitalization preceding the missing data observation. In this case, the missing observation was assigned the worst-rank score relative to those actually observed and was assigned a rank reflecting the relative order of the actual event times. Baseline 6MWD comprised of an average of the last two consecutive measurements prior to randomization that varied by no greater than 10%. If only one measurement was available, that measurement was used. If no two consecutive measures vary by no greater than 10% then Baseline was based on the last two consecutive measures for a participant.
Time Frame
Baseline and Week 24
Title
Change From Baseline in the World Health Organization Functional Class at Week 24
Description
The WHO Functional Class (FC) indicates the severity of PAH and is an adaptation of the New York Heart Association classification. It was assessed by the investigator. There are four grades for WHO FC based on severity of symptoms (Class I = none, Class IV = most severe). Baseline WHO FC is the latest assessment prior to dosing (i.e., at Randomization or Screening). Change from Baseline at Week 24 was calculated as the Week 24 value minus the Baseline value. The analysis was performed based on the last observation carried forward data, except in the case of an adjudicated clinical failure event of death or hospitalization preceding the missing data observation. In this case, the missing observations was assigned the worst-rank score relative to those actually observed and was assigned rank reflecting the relative order of the actual event times.
Time Frame
Baseline and Week 24
Title
Change From Baseline in Borg Dyspnea Index at Week 24
Description
Borg Dyspnea Index (BDI) indicates the degree of breathlessness after completion of the 6 minute walk test. The BDI was calculated by using the Borg category (C) ratio (R) CR10 scale which starts at 0 (nothing at all) and has no upper limit (extremely strong). Change from BL was calculated as the Week 24 values minus the BL value. The BDI scale was assessed by each participant. The BL BDI score is the average of the two BDI values obtained following the two 6MWD tests used in determining the BL 6MWD. A negative change from BL in the BDI score represented an improvement for the participant. The analysis was performed based on the last observation carried forward data, except in the case of an adjudicated clinical failure event of death or hospitalization preceding the missing data observation. In this case, the missing observation was assigned the worst-rank score relative to those actually observed and was assigned rank reflecting the relative order of the actual event times.
Time Frame
Baseline (BL) and Week 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
GSK Investigational Site
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36617
Country
United States
Facility Name
GSK Investigational Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85012
Country
United States
Facility Name
GSK Investigational Site
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
GSK Investigational Site
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
GSK Investigational Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90073
Country
United States
Facility Name
GSK Investigational Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
GSK Investigational Site
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
GSK Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
GSK Investigational Site
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
GSK Investigational Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
GSK Investigational Site
City
Kissimmee
State/Province
Florida
ZIP/Postal Code
34741
Country
United States
Facility Name
GSK Investigational Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
GSK Investigational Site
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
GSK Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
GSK Investigational Site
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States
Facility Name
GSK Investigational Site
City
Oakbrook Terrace
State/Province
Illinois
ZIP/Postal Code
60181
Country
United States
Facility Name
GSK Investigational Site
City
Carmel
State/Province
Indiana
ZIP/Postal Code
46032
Country
United States
Facility Name
GSK Investigational Site
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
GSK Investigational Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
GSK Investigational Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
GSK Investigational Site
City
Portland
State/Province
Maine
ZIP/Postal Code
04102
Country
United States
Facility Name
GSK Investigational Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
GSK Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
GSK Investigational Site
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
GSK Investigational Site
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
GSK Investigational Site
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
GSK Investigational Site
City
Troy
State/Province
Michigan
ZIP/Postal Code
48085
Country
United States
Facility Name
GSK Investigational Site
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
GSK Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
Facility Name
GSK Investigational Site
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07962
Country
United States
Facility Name
GSK Investigational Site
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07112
Country
United States
Facility Name
GSK Investigational Site
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11040
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
GSK Investigational Site
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
GSK Investigational Site
City
Rochester
State/Province
New York
ZIP/Postal Code
14623
Country
United States
Facility Name
GSK Investigational Site
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28803
Country
United States
Facility Name
GSK Investigational Site
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
GSK Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
GSK Investigational Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
GSK Investigational Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
GSK Investigational Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
GSK Investigational Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97220
Country
United States
Facility Name
GSK Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
GSK Investigational Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19140
Country
United States
Facility Name
GSK Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
GSK Investigational Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
GSK Investigational Site
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02903
Country
United States
Facility Name
GSK Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
GSK Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
GSK Investigational Site
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
GSK Investigational Site
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
GSK Investigational Site
City
Murray
State/Province
Utah
ZIP/Postal Code
84157
Country
United States
Facility Name
GSK Investigational Site
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
GSK Investigational Site
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
GSK Investigational Site
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
GSK Investigational Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
GSK Investigational Site
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
GSK Investigational Site
City
Darlinghurst
State/Province
New South Wales
ZIP/Postal Code
2010
Country
Australia
Facility Name
GSK Investigational Site
City
Chermside
State/Province
Queensland
ZIP/Postal Code
4032
Country
Australia
Facility Name
GSK Investigational Site
City
Hobart
State/Province
Tasmania
ZIP/Postal Code
7000
Country
Australia
Facility Name
GSK Investigational Site
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
GSK Investigational Site
City
Perth
State/Province
Western Australia
ZIP/Postal Code
6000
Country
Australia
Facility Name
GSK Investigational Site
City
Innsbruck
ZIP/Postal Code
A-6020
Country
Austria
Facility Name
GSK Investigational Site
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Facility Name
GSK Investigational Site
City
Brussels
ZIP/Postal Code
1070
Country
Belgium
Facility Name
GSK Investigational Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
GSK Investigational Site
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T1Y 6J4
Country
Canada
Facility Name
GSK Investigational Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V5Z 1M9
Country
Canada
Facility Name
GSK Investigational Site
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3A 1R8
Country
Canada
Facility Name
GSK Investigational Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2N2
Country
Canada
Facility Name
GSK Investigational Site
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1V 4G5
Country
Canada
Facility Name
GSK Investigational Site
City
Brest
ZIP/Postal Code
29200
Country
France
Facility Name
GSK Investigational Site
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
GSK Investigational Site
City
La Tronche
ZIP/Postal Code
38700
Country
France
Facility Name
GSK Investigational Site
City
Le Kremlin-Bicêtre cedex
ZIP/Postal Code
94275
Country
France
Facility Name
GSK Investigational Site
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
GSK Investigational Site
City
Marseille cedex 20
ZIP/Postal Code
13915
Country
France
Facility Name
GSK Investigational Site
City
Montpellier cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
GSK Investigational Site
City
Pessac cedex
ZIP/Postal Code
33604
Country
France
Facility Name
GSK Investigational Site
City
Saint Pierre cedex
ZIP/Postal Code
97448
Country
France
Facility Name
GSK Investigational Site
City
Toulouse cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
GSK Investigational Site
City
Vandoeuvre-les-Nancy
ZIP/Postal Code
54511
Country
France
Facility Name
GSK Investigational Site
City
Freiburg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
GSK Investigational Site
City
Heidelberg
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
69126
Country
Germany
Facility Name
GSK Investigational Site
City
Loewenstein
State/Province
Baden-Wuerttemberg
ZIP/Postal Code
74245
Country
Germany
Facility Name
GSK Investigational Site
City
Muenchen
State/Province
Bayern
ZIP/Postal Code
81377
Country
Germany
Facility Name
GSK Investigational Site
City
Regensburg
State/Province
Bayern
ZIP/Postal Code
93053
Country
Germany
Facility Name
GSK Investigational Site
City
Wuerzburg
State/Province
Bayern
ZIP/Postal Code
97074
Country
Germany
Facility Name
GSK Investigational Site
City
Giessen
State/Province
Hessen
ZIP/Postal Code
35392
Country
Germany
Facility Name
GSK Investigational Site
City
Greifswald
State/Province
Mecklenburg-Vorpommern
ZIP/Postal Code
17475
Country
Germany
Facility Name
GSK Investigational Site
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
GSK Investigational Site
City
Bonn
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
53127
Country
Germany
Facility Name
GSK Investigational Site
City
Koeln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
50937
Country
Germany
Facility Name
GSK Investigational Site
City
Homburg
State/Province
Saarland
ZIP/Postal Code
66421
Country
Germany
Facility Name
GSK Investigational Site
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany
Facility Name
GSK Investigational Site
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04103
Country
Germany
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
12559
Country
Germany
Facility Name
GSK Investigational Site
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
GSK Investigational Site
City
Alexandroupolis
ZIP/Postal Code
68100
Country
Greece
Facility Name
GSK Investigational Site
City
Athens
ZIP/Postal Code
124 62
Country
Greece
Facility Name
GSK Investigational Site
City
Athens
ZIP/Postal Code
176 74
Country
Greece
Facility Name
GSK Investigational Site
City
Thessaloniki
ZIP/Postal Code
54636
Country
Greece
Facility Name
GSK Investigational Site
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
Facility Name
GSK Investigational Site
City
Roma
State/Province
Lazio
ZIP/Postal Code
00161
Country
Italy
Facility Name
GSK Investigational Site
City
Cagliari
State/Province
Sardegna
ZIP/Postal Code
09134
Country
Italy
Facility Name
GSK Investigational Site
City
Catania
State/Province
Sicilia
ZIP/Postal Code
95100
Country
Italy
Facility Name
GSK Investigational Site
City
Pisa
State/Province
Toscana
ZIP/Postal Code
56124
Country
Italy
Facility Name
GSK Investigational Site
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Facility Name
GSK Investigational Site
City
Hokkaido
ZIP/Postal Code
060-8648
Country
Japan
Facility Name
GSK Investigational Site
City
Shizuoka
ZIP/Postal Code
431-3192
Country
Japan
Facility Name
GSK Investigational Site
City
Tokyo
ZIP/Postal Code
113-8655
Country
Japan
Facility Name
GSK Investigational Site
City
Amsterdam
ZIP/Postal Code
1081 HV
Country
Netherlands
Facility Name
GSK Investigational Site
City
Maastricht
ZIP/Postal Code
6229 HX
Country
Netherlands
Facility Name
GSK Investigational Site
City
Rotterdam
ZIP/Postal Code
3015 CE
Country
Netherlands
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
GSK Investigational Site
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
GSK Investigational Site
City
Córdoba
ZIP/Postal Code
14004
Country
Spain
Facility Name
GSK Investigational Site
City
L'Hospitalet de Llobregat
ZIP/Postal Code
08907
Country
Spain
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Facility Name
GSK Investigational Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Facility Name
GSK Investigational Site
City
Majadahonda (Madrid)
ZIP/Postal Code
28222
Country
Spain
Facility Name
GSK Investigational Site
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
GSK Investigational Site
City
Palma de Mallorca
ZIP/Postal Code
07010
Country
Spain
Facility Name
GSK Investigational Site
City
Santander
ZIP/Postal Code
39008
Country
Spain
Facility Name
GSK Investigational Site
City
Santiago de Compostela
ZIP/Postal Code
15706
Country
Spain
Facility Name
GSK Investigational Site
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
GSK Investigational Site
City
Toledo
ZIP/Postal Code
45004
Country
Spain
Facility Name
GSK Investigational Site
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
GSK Investigational Site
City
Göteborg
ZIP/Postal Code
SE-413 45
Country
Sweden
Facility Name
GSK Investigational Site
City
Linköping
ZIP/Postal Code
SE-581 85
Country
Sweden
Facility Name
GSK Investigational Site
City
Lund
ZIP/Postal Code
SE-221 85
Country
Sweden
Facility Name
GSK Investigational Site
City
Umeå
ZIP/Postal Code
SE-901 85
Country
Sweden
Facility Name
GSK Investigational Site
City
Uppsala
ZIP/Postal Code
SE-751 85
Country
Sweden
Facility Name
GSK Investigational Site
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB3 8RE
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Clydebank
ZIP/Postal Code
G81 4DY
Country
United Kingdom
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
NW3 2QH
Country
United Kingdom
Facility Name
GSK Investigational Site
City
London
ZIP/Postal Code
SW3 6NP
Country
United Kingdom
Facility Name
GSK Investigational Site
City
Sheffield
ZIP/Postal Code
S10 2JF
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
32161055
Citation
Kuwana M, Blair C, Takahashi T, Langley J, Coghlan JG. Initial combination therapy of ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) in the modified intention-to-treat population of the AMBITION study: post hoc analysis. Ann Rheum Dis. 2020 May;79(5):626-634. doi: 10.1136/annrheumdis-2019-216274. Epub 2020 Mar 11. Erratum In: Ann Rheum Dis. 2020 Sep;79(9):e118.
Results Reference
derived
PubMed Identifier
31511080
Citation
White RJ, Vonk-Noordegraaf A, Rosenkranz S, Oudiz RJ, McLaughlin VV, Hoeper MM, Grunig E, Ghofrani HA, Chakinala MM, Barbera JA, Blair C, Langley J, Frost AE. Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension. Respir Res. 2019 Sep 12;20(1):208. doi: 10.1186/s12931-019-1180-1.
Results Reference
derived
PubMed Identifier
28039187
Citation
Coghlan JG, Galie N, Barbera JA, Frost AE, Ghofrani HA, Hoeper MM, Kuwana M, McLaughlin VV, Peacock AJ, Simonneau G, Vachiery JL, Blair C, Gillies H, Miller KL, Harris JHN, Langley J, Rubin LJ; AMBITION investigators. Initial combination therapy with ambrisentan and tadalafil in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH): subgroup analysis from the AMBITION trial. Ann Rheum Dis. 2017 Jul;76(7):1219-1227. doi: 10.1136/annrheumdis-2016-210236. Epub 2016 Dec 30.
Results Reference
derived
PubMed Identifier
26308684
Citation
Galie N, Barbera JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin VV, Peacock AJ, Simonneau G, Vachiery JL, Grunig E, Oudiz RJ, Vonk-Noordegraaf A, White RJ, Blair C, Gillies H, Miller KL, Harris JH, Langley J, Rubin LJ; AMBITION Investigators. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med. 2015 Aug 27;373(9):834-44. doi: 10.1056/NEJMoa1413687.
Results Reference
derived
PubMed Identifier
26196225
Citation
Peacock AJ, Zamboni W, Vizza CD. Ambrisentan for the treatment of adults with pulmonary arterial hypertension: a review. Curr Med Res Opin. 2015;31(9):1793-807. doi: 10.1185/03007995.2015.1074890. Epub 2015 Aug 27.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs