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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00380068




Registration number
NCT00380068
Ethics application status
Date submitted
21/09/2006
Date registered
25/09/2006
Date last updated
5/04/2012

Titles & IDs
Public title
Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
Scientific title
ARIES-3: A Phase 3, Long-Term, Open-Label, Multicenter Safety and Efficacy Study of Ambrisentan in Subjects With Pulmonary Hypertension
Secondary ID [1] 0 0
ARIES-3
Secondary ID [2] 0 0
AMB-323
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Hypertension 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Hypertension
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ambrisentan

Experimental: Ambrisentan -


Treatment: Drugs: Ambrisentan
Oral tablets taken once daily.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline to Week 24 in 6 Minute Walk Distance (6MWD)
Timepoint [1] 0 0
Baseline to Week 24
Secondary outcome [1] 0 0
Change From Baseline to Week 24 in Borg Dyspnea Index - Change from Baseline to Week 24 in Borg Dyspnea Index. The Borg Dyspnea Index of Perceived Exertion Scores range from 0 to 10. Best and Worst values are: 0 (Best) to 10 (Worst). Scales are described as rating of breathlessness and its description: 0= none; 0.5= very,very slight (just noticeable); 1= very slight; 2=slight; 3= moderate; 4= somewhat severe; 5= severe; 6 (in between severe and very severe); 7= very severe; 8 (in between very, very severe and maximum); 9= very, very severe; and 10= maximum.
Timepoint [1] 0 0
Baseline to Week 24
Secondary outcome [2] 0 0
Change From Baseline to Week 48 in Borg Dyspnea Index - Change from Baseline to Week 48 in Borg Dyspnea Index. The Borg Dyspnea Index of Perceived Exertion Scores range from 0 to 10. Best and Worst values are: 0 (Best) to 10 (Worst). Scales are described as rating of breathlessness and its description: 0= none; 0.5= very,very slight (just noticeable); 1= very slight; 2=slight; 3= moderate; 4= somewhat severe; 5= severe; 6 (in between severe and very severe); 7= very severe; 8 (in between very, very severe and maximum); 9= very, very severe; and 10= maximum.
Timepoint [2] 0 0
Baseline to Week 48
Secondary outcome [3] 0 0
Percent Change From Baseline to Week 24 in B-type Natriuretic Peptide (BNP)
Timepoint [3] 0 0
Baseline to Week 24
Secondary outcome [4] 0 0
Percent Change From Baseline to Week 48 in BNP
Timepoint [4] 0 0
Baseline to Week 48
Secondary outcome [5] 0 0
Change From Baseline to Week 24 in WHO Functional Class - Change from baseline in World Health Organization functional class (WHO) at Week 24 is the incidence of participants that improved, had no change, or worsened. WHO categories are 1 to 4 with the worse category at 4. Improvement = a category change from baseline of <= -1: change of -3 (eg, WHO from 4 to 1), change of -2 (eg, WHO from 3 to 1), change of -1 (eg, WHO from 2 to 1). Inversely, participants worsening are those with a category change from baseline of at least +1. No change in WHO functional class represents the percentage of participants with a change in category from baseline of 0.
Timepoint [5] 0 0
Baseline to Week 24
Secondary outcome [6] 0 0
Change From Baseline to Week 48 in WHO Functional Class - Change from baseline in WHO at Week 48 is expressed as the incidence of participants that improved, had no change or worsened. WHO categories range from 1 to 4 with the worse category at 4. Improvement = a category change from baseline of <= -1: change of -3 (eg, WHO from 4 to 1), change of -2 (eg, WHO from 3 to 1), change of -1 (eg, WHO from 2 to 1). Inversely, participants worsening are those with a category change from baseline of at least +1. No change in WHO functional class represents the percentage of participants with a change in category from baseline of 0.
Timepoint [6] 0 0
Baseline to Week 48
Secondary outcome [7] 0 0
Change From Baseline to Week 24 in SF-36 Health Survey Physical Functioning Scale - Change from baseline to Week 24 in the SF-36 health survey physical functioning scale. 10 activities rated by health limitations using 3 categories (1= Yes, limited a lot; 2= Yes, limited a little; and 3= No, not limited at all). The best score is 3 and the worst score is 1. Scores are transformed by subtracting the unit by the lowest raw score and dividing by the raw score range. The scores are then standardized with the 1998 General United States (US) population mean and standard deviation (SD). Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.
Timepoint [7] 0 0
Baseline to Week 24
Secondary outcome [8] 0 0
Change From Baseline to Week 48 in SF-36 Health Survey Physical Functioning Scale - Change from baseline to Week 48 in the SF-36 health survey physical functioning scale. 10 activities are rated by health limitations using 3 categories (1= Yes, limited a lot; 2= Yes, limited a little; and 3= No, not limited at all). The best score is 3 and the worst score is 1. Scores are transformed by subtracting the unit by the lowest raw score and dividing by the raw score range. The scores are then standardized with the 1998 General US population mean and standard deviation. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and standard deviation of 10.
Timepoint [8] 0 0
Baseline to Week 48
Secondary outcome [9] 0 0
Percent of Participants With no Clinical Worsening of Pulmonary Hypertension (PH) at Week 24 - Clinical worsening: occurrence of death, lung transplantation, hospitalization for PH, atrial septostomy, a change to chronic prostanoid or sildenafil treatment due to protocol-defined worsening criteria, or study withdrawal due to the addition of other clinically approved PH therapeutic agents
Timepoint [9] 0 0
Baseline to Week 24
Secondary outcome [10] 0 0
Percent of Participants With no Clinical Worsening of PH at Week 48 - Clinical worsening: occurrence of death, lung transplantation, hospitalization for PH, atrial septostomy, a change to chronic prostanoid or sildenafil treatment due to protocol-defined worsening criteria, or study withdrawal due to the addition of other clinically approved PH therapeutic agents
Timepoint [10] 0 0
Baseline to Week 48
Secondary outcome [11] 0 0
Failure-free Treatment Status - Defined by occurrence of death, lung transplantation, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents
Timepoint [11] 0 0
Baseline to Week 24
Secondary outcome [12] 0 0
Failure-free Treatment Status - Defined by occurrence of death, lung transplantation, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents
Timepoint [12] 0 0
Baseline to Week 48
Secondary outcome [13] 0 0
Monotherapy Treatment Status - Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment
Timepoint [13] 0 0
Baseline to Week 24
Secondary outcome [14] 0 0
Monotherapy Treatment Status - Defined by no addition of sildenafil, iloprost, treprostinil, or epoprostenol to ongoing ambrisentan treatment
Timepoint [14] 0 0
Baseline to Week 48
Secondary outcome [15] 0 0
Long-term Survival - Defined as not dying during study participation
Timepoint [15] 0 0
Baseline to Week 24
Secondary outcome [16] 0 0
Long-term Survival - Defined as not dying during study participation
Timepoint [16] 0 0
Baseline to Week 48

Eligibility
Key inclusion criteria
Summarized

1. 18 years of age or older

2. Current diagnosis of PH associated with an acceptable etiology as outlined in the
protocol, including: PH due to the following etiologies: 1) PAH including idiopathic
and familial PAH and PAH associated with collagen vascular disease, congenital
systemic-to-pulmonary shunts (including Eisenmenger's syndrome), human
immunodeficiency virus (HIV) infection, drugs and toxins, thyroid disorders, glycogen
storage disease, Gaucher disease, hemoglobinopathies, and splenectomy (WHO Group 1);
2) PH associated with lung diseases and/or hypoxemia, including chronic obstructive
pulmonary disease (COPD), interstitial lung disease (ILD), sleep-disordered breathing,
and alveolar hypoventilation disorders (WHO Group 3); 3) PH due to proximal or distal
chronic thromboembolic obstruction (WHO Group 4); and 4) PH due to sarcoidosis (WHO
Group 5).

3. Stable regimen (within four weeks) of chronic prostanoid, PDE-5 inhibitor, calcium
channel blocker, or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
inhibitor therapy

4. Right heart catheterization completed prior to screening must meet pre-specified
criteria

5. Female participants of childbearing potential must have a negative serum pregnancy
test and must agree to use a reliable double method of contraception until study
completion and for at least four weeks following their final study visit.

6. Male participants must be informed of the potential risks of testicular tubular
atrophy and infertility associated with taking ambrisentan and queried regarding his
understanding of the potential risks as described in the Informed Consent Form.

Summarized
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participation in a previous clinical study with ambrisentan

2. Bosentan or sitaxsentan use within four weeks prior to the screening visit

3. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) lab value that is
greater than 3 times the upper limit of normal at the screening visit

4. Pulmonary function tests not meeting the following pre-specified criteria: 1) mean
pulmonary arterial pressure (PAP) >= 25 mm Hg; 2) PVR > 3 mm Hg/L/min; 3) pulmonary
capillary wedge pressure (PCWP) or left ventricle end diastolic pressure (LVEDP) < 15
mm Hg; 4) total lung capacity (TLC) >= 70% of predicted normal for participants
without ILD or >= 60% of predicted normal in participants with ILD; forced expiratory
volume in 1 second (FEV1) >= 65% of predicted normal in participants without COPD or
>= 50% of predicted normal in participants with COPD

5. Contraindication to treatment with endothelin receptor antagonist (ERA)

6. History of malignancies other than basal cell carcinoma of the skin or in situ
carcinoma of the cervix within the past five years

7. Female participant who is pregnant or breastfeeding

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
St. Vincent's Hospital - Darlinghurst
Recruitment hospital [2] 0 0
Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Massachusetts
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
State/province [15] 0 0
New York
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Ohio
Country [18] 0 0
United States of America
State/province [18] 0 0
Oregon
Country [19] 0 0
United States of America
State/province [19] 0 0
Pennsylvania
Country [20] 0 0
United States of America
State/province [20] 0 0
Rhode Island
Country [21] 0 0
United States of America
State/province [21] 0 0
South Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
Canada
State/province [24] 0 0
Alberta
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this study was to evaluate the safety and efficacy of ambrisentan in
a broad population of participants with pulmonary hypertension (PH). Secondary objectives of
this study were to evaluate the effects of ambrisentan on other clinical measures of
pulmonary arterial hypertension (PAH), long-term treatment success, and survival.
Trial website
https://clinicaltrials.gov/show/NCT00380068
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Lewis J Rubin, MD
Address 0 0
University of California, San Diego
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications