Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000170426
Ethics application status
Approved
Date submitted
13/02/2007
Date registered
14/03/2007
Date last updated
14/03/2007
Type of registration
Retrospectively registered

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 Study of the Safety and Efficacy of Ambrisentan in Subjects with Pulmonary Hypertension
Secondary ID [1] 350 0
Gilead Sciences Inc: AMB-323
Universal Trial Number (UTN)
Trial acronym
ARIES-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Hypertension 1685 0
Condition category
Condition code
Cardiovascular 1780 1780 0 0
Hypertension

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a long-term, open-label study of a new experimental drug called ambrisentan. The purpose of this study is to evaluate the safety and efficacy of ambrisentan in a broad population of subjects with pulmonary arterial hypertension (PAH). Secondarily, this study will evaluate the effects of ambrisentan on other clinical measures of PAH, long-term treatment success, and survival. Subjects will receive 5 mg ambrisentan each day by mouth for the first 24 weeks. Then, subjects may receive 2.5, 5, or 10 mg each day by mouth, based on investigator discretion as clinically indicated. Each day of study participation subjects will receive ambrisentan until the study is ended or the subject discontinues study participation. Subjects may continue to receive ambrisentan until such time as the investigator or subject chooses to stop ambrisentan treatment, the cumulative adverse event profile does not warrant continuation of the study, ambrisentan becomes commercially available, or Gilead Sciences, Inc., stops the study.
Intervention code [1] 1597 0
Treatment: Drugs
Comparator / control treatment
No comparator.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 2487 0
Change from baseline in the 6-minute walk distance (6MWD). The 6MWD is the longest possible distance that a subject can walk in a timed 6-minute interval.
Timepoint [1] 2487 0
The 6MWD will be assessed at baseline, weeks 4, 12 and 24.
Secondary outcome [1] 4288 0
1) Clinical worsening of PAH
Timepoint [1] 4288 0
Events that mark the natural history of disease progression. These events will be assessed when or if they occur for each subject, and the event outcome will be recorded at the time of occurence. The occurrence of these events will be monitored for the duration of subject participation, until the study is ended or the subject discontinues study participation.
Secondary outcome [2] 4289 0
2) Change from baseline in (i) World Health Organisation (WHO) functional class, (ii) SF-36 heath survey, (iii) Borg dyspnea index, (iv) B-type natriuretic peptide
Timepoint [2] 4289 0
Measured at baseline, again at Weeks 4, 12, and 24, and every 6 month thereafter from Week 24 until the end of the study or the subject discontinues study participation.
Secondary outcome [3] 4290 0
3) Monotherapy treatment status
Timepoint [3] 4290 0
Events that mark the natural history of disease progression. These events will be assessed when or if they occur for each subject, and the event outcome will be recorded at the time of occurence. The occurrence of these events will be monitored for the duration of subject participation, until the study is ended or the subject discontinues study participation.
Secondary outcome [4] 4291 0
4) Failure-free treatment status
Timepoint [4] 4291 0
Events that mark the natural history of disease progression. These events will be assessed when or if they occur for each subject, and the event outcome will be recorded at the time of occurence. The occurrence of these events will be monitored for the duration of subject participation, until the study is ended or the subject discontinues study participation.
Secondary outcome [5] 4292 0
5) Long-term survival.
Timepoint [5] 4292 0
Events that mark the natural history of disease progression. These events will be assessed when or if they occur for each subject, and the event outcome will be recorded at the time of occurence. The occurrence of these events will be monitored for the duration of subject participation, until the study is ended or the subject discontinues study participation.

Eligibility
Key inclusion criteria
1) Current diagnosis of PAH associated with an acceptable etiology as outlined in the protocol (i.e., idiopathic pulmonary arterial hypertension, familial pulmonary hypertension, PAH associated with interstitial lung disease, PAH due to chronic thromboembolic disease or sickle cell disease, PAH associated with chronic obstructive pulmonary disease, and associated PAH secondary to the scleroderma spectrum of disease, systemic lupus, erythematosus, anorexigen use, congenital heart defects, or human immunodeficiency virus (HIV) infection); 2) Receiving stable, chronic prostanoid treatment or oral phosphodiesterase type 5 (PDE-5) inhibitors for 4 weeks prior to the Screening Visit; 3) Receiving stable calcium channel blocker treatment or 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors for 4 weeks prior to the Screening Visit; 4) Right heart catheterization completed within 1 year prior to the Screening Visit and fulfilling all pre-specified criteria; 5) Pulmonary function tests fulfilling all pre-specified criteria; 6) Aminotransferase concentrations less than 1.5x the Upper Limit of Normal (ULN) at the Screening Visit; 7) Male and female subjects may be eligible for study participation; however, female subjects 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 4 weeks following their final study visit; 8) Male subjects 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.
Minimum age
18 Years
Maximum age
Not stated
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Participation in a previous clinical study with ambrisentan;2) Treatment with bosentan or sitaxsentan within four weeks prior to the Screening Visit;3) Contraindication to treatment with endothelin receptor antagonists (ERAs);4) History of malignancies within 5 years prior to the Screening Visit, with the exception of basal cell carcinoma of the skin or in situ carcinoma of the cervix;5) Female subject 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
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
15/12/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment outside Australia
Country [1] 484 0
United States of America
State/province [1] 484 0

Funding & Sponsors
Funding source category [1] 1930 0
Commercial sector/Industry
Name [1] 1930 0
Gilead Science, Inc.
Country [1] 1930 0
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences, Inc.
Address
Country
United States of America
Secondary sponsor category [1] 1742 0
None
Name [1] 1742 0
Nil
Address [1] 1742 0
Country [1] 1742 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 3596 0
St Vincent’s Hospital-St. Vincent's Hospital HREC
Ethics committee address [1] 3596 0
St. Vincent's Hospital Limited, Victoria Street Darlinghurst NSW 2010
Ethics committee country [1] 3596 0
Australia
Date submitted for ethics approval [1] 3596 0
Approval date [1] 3596 0
20/11/2006
Ethics approval number [1] 3596 0
Ethics committee name [2] 3597 0
Royal Perth Hospital-Royal Perth Hospital EC
Ethics committee address [2] 3597 0
Royal Perth Hospital, Wellington Street Perth WA 6000
Ethics committee country [2] 3597 0
Australia
Date submitted for ethics approval [2] 3597 0
Approval date [2] 3597 0
28/09/2006
Ethics approval number [2] 3597 0

Summary
Brief summary
This is a long-term, open-label study of a new experimental drug called ambrisentan. The purpose of this study is to evaluate the safety and efficacy of ambrisentan in a broad population of subjects with pulmonary arterial hypertension (PAH). Secondarily, this study will evaluate the effects of ambrisentan on other clinical measures of PAH, long-term treatment success, and survival.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27531 0
Address 27531 0
Country 27531 0
Phone 27531 0
Fax 27531 0
Email 27531 0
Contact person for public queries
Name 10786 0
Kathleen DeHaven
Address 10786 0
Gilead Colorado, Inc.
7575 West 103rd Ave., #102
Westminster CO, 80021-5426
Country 10786 0
United States of America
Phone 10786 0
0011 303-410-6666
Fax 10786 0
Email 10786 0
[email protected]
Contact person for scientific queries
Name 1714 0
Kathleen DeHaven
Address 1714 0
Gilead Colorado, Inc.
7575 West 103rd Ave.
#102
Westminster CO 80021-5426
Country 1714 0
United States of America
Phone 1714 0
0011 303-410-6666
Fax 1714 0
Email 1714 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
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Documents added automatically
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