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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00424021




Registration number
NCT00424021
Ethics application status
Date submitted
17/01/2007
Date registered
18/01/2007
Date last updated
27/01/2012

Titles & IDs
Public title
Phase 2 Extension Study of Ambrisentan in Pulmonary Arterial Hypertension
Scientific title
An Open-Label, Long-Term Study of Ambrisentan in Pulmonary Hypertension Subjects Having Completed Myogen Study AMB-220
Secondary ID [1] 0 0
AMB-220-E
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
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Cardiovascular 0 0 0 0
Hypertension

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

Treatment: Drugs: ambrisentan
1, 2.5, 5, and 10 mg ambrisentan given orally once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Pulmonary Arterial Hypertension (PAH) Who Completed the Phase II NCT00046319 Study and Who Experienced Severe Adverse Events (AEs) During Long-term Ambrisentan Exposure
Assessment method [1] 0 0
The number of participants in the AMB-220-E analysis set who experienced AEs (including serious AEs) of severe severity (ie, made it impossible to perform routine activities and the subject may have experienced intolerable discomfort or pain) that began after entering AMB-220-E (treatment-emergent AEs) and that occurred in more than 1 participant are summarized by dose group. The AMB-220-E analysis set consisted of all participants who received at least 1 dose of study drug during the AMB-220-E study.
Timepoint [1] 0 0
Week 24 (AMB-220-E baseline) to Week 334
Primary outcome [2] 0 0
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure
Assessment method [2] 0 0
The number of participants in the AMB-220-E analysis set who experienced AEs (including serious AEs) of moderate severity (ie, interfered with routine activities and subject may have experienced significant discomfort) that began after entering AMB-220-E (treatment-emergent AEs) and that occurred in more than 1 participant are summarized by dose group. The AMB-220-E analysis set consisted of all participants who received at least 1 dose of study drug during the AMB-220-E study.
Timepoint [2] 0 0
Week 24 (AMB-220-E baseline) to Week 329.3
Primary outcome [3] 0 0
Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure
Assessment method [3] 0 0
The number of participants in the AMB-220-E analysis set who experienced AEs (including serious AEs) of mild severity (ie, did not interfere with routine activities and the subject may have experienced slight discomfort) that began after entering AMB-220-E (treatment-emergent AEs) and that occurred in more than 1 participant are summarized by dose group. The AMB-220-E analysis set consisted of all participants who received at least 1 dose of study drug during the AMB-220-E study.
Timepoint [3] 0 0
Week 24 (AMB-220-E baseline) to Week 329.3
Secondary outcome [1] 0 0
Baseline Measurement in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (Baseline [Week 24])
Assessment method [1] 0 0
The 6MWT was conducted according to the American Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.) Primary efficacy analyses were performed for the AMB-220-E analysis set (all subjects who received at least 1 dose of study drug during the AMB-220-E study).
Timepoint [1] 0 0
Week 24 (AMB-220-E baseline)
Secondary outcome [2] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (Last Observation Carried Forward [LOCF]) (Week 48)
Assessment method [2] 0 0
The 6MWT was conducted according to the American Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.) Primary efficacy analyses were performed for the AMB-220-E analysis set (all subjects who received at least 1 dose of study drug during the AMB-220-E study).
Timepoint [2] 0 0
24 weeks (Week 24 to Week 48)
Secondary outcome [3] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (LOCF) (Week 108)
Assessment method [3] 0 0
The 6MWT was conducted according to the American Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.) Primary efficacy analyses were performed for the AMB-220-E analysis set (all subjects who received at least 1 dose of study drug during the AMB-220-E study).
Timepoint [3] 0 0
84 weeks (Week 24 to Week 108)
Secondary outcome [4] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (LOCF) (Week 156)
Assessment method [4] 0 0
The 6MWT was conducted according to the American Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.) Primary efficacy analyses were performed for the AMB-220-E analysis set (all subjects who received at least 1 dose of study drug during the AMB-220-E study).
Timepoint [4] 0 0
132 weeks (Week 24 to Week 156)
Secondary outcome [5] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (LOCF) (Week 204)
Assessment method [5] 0 0
The 6MWT was conducted according to the American Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.) Primary efficacy analyses were performed for the AMB-220-E analysis set (all subjects who received at least 1 dose of study drug during the AMB-220-E study).
Timepoint [5] 0 0
180 weeks (Week 24 to Week 204)
Secondary outcome [6] 0 0
Baseline Measurement in Exercise Capacity as Measured by the Borg Dyspnea Index (BDI) (Baseline [Week 24])
Assessment method [6] 0 0
Change from baseline evaluated after 24 (baseline), 48, 108, 156, and 204 weeks of ambrisentan therapy in BDI (measured as units on a scale) immediately following exercise. Borg Dyspnea Index, a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Timepoint [6] 0 0
Week 24 (AMB-220-E baseline)
Secondary outcome [7] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 48)
Assessment method [7] 0 0
Change from baseline evaluated after 24 (baseline), 48, 108, 156, and 204 weeks of ambrisentan therapy in BDI (measured as units on a scale) immediately following exercise. Borg Dyspnea Index, a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Timepoint [7] 0 0
24 weeks (Week 24 to Week 48)
Secondary outcome [8] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 108)
Assessment method [8] 0 0
Change from baseline evaluated after 24 (baseline), 48, 108, 156, and 204 weeks of ambrisentan therapy in BDI (measured as units on a scale) immediately following exercise. Borg Dyspnea Index, a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Timepoint [8] 0 0
84 weeks (Week 24 to Week 108)
Secondary outcome [9] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 156)
Assessment method [9] 0 0
Change from baseline evaluated after 24 (baseline), 48, 108, 156, and 204 weeks of ambrisentan therapy in BDI (measured as units on a scale) immediately following exercise. Borg Dyspnea Index, a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Timepoint [9] 0 0
132 weeks (Week 24 to Week 156)
Secondary outcome [10] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 204)
Assessment method [10] 0 0
Change from baseline evaluated after 24 (baseline), 48, 108, 156, and 204 weeks of ambrisentan therapy in BDI (measured as units on a scale) immediately following exercise. Borg Dyspnea Index, a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Timepoint [10] 0 0
180 weeks (Week 24 to Week 204)
Secondary outcome [11] 0 0
Baseline Measurement in Exercise Capacity as Measured by the World Health Organization (WHO) Functional Classification (Baseline [Week 24])
Assessment method [11] 0 0
Classes: I) pulmonary hypertension (PH); ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possibly at rest.
Timepoint [11] 0 0
Week 24 (AMB-220-E baseline)
Secondary outcome [12] 0 0
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 24 Weeks of Treatment in AMB-220-E
Assessment method [12] 0 0
Classes: I) PH; ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possibly at rest.
Timepoint [12] 0 0
24 weeks (Week 24 [baseline of AMB-220-E] to Week 48)
Secondary outcome [13] 0 0
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 84 Weeks of Treatment in AMB-220-E
Assessment method [13] 0 0
Classes: I) PH; ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possibly at rest.
Timepoint [13] 0 0
84 weeks (Week 24 of NCT00046319 to Week 108)
Secondary outcome [14] 0 0
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 132 Weeks of Treatment in AMB-220-E
Assessment method [14] 0 0
Classes: I) PH; ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possibly at rest.
Timepoint [14] 0 0
132 weeks (Week 24 of NCT00046319 to Week 156)
Secondary outcome [15] 0 0
Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 180 Weeks of Treatment in AMB-220-E
Assessment method [15] 0 0
Classes: I) PH; ordinary physical activity not limited or causes increased dyspnea, fatigue, chest pain, or presyncope. II) PH; ordinary physical activity mildly limited and causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. III) PH; physical activity markedly limited and less than ordinary physical activity causes increased dyspnea, fatigue, chest pain, or presyncope; comfortable at rest. IV) PH; physical activity causes symptoms; signs of right heart failure; dyspnea/fatigue possibly at rest.
Timepoint [15] 0 0
180 weeks (Week 24 of NCT00046319 to Week 204)
Secondary outcome [16] 0 0
Baseline Measurement in Exercise Capacity as Measured by the Subject Global Assessment (SGA) (Baseline [Week 24])
Assessment method [16] 0 0
The SGA was determined using a visual-analog scale. Subjects were asked the question, "How are you feeling today?" and were asked to draw a vertical mark on a 100-mm horizontal line in which zero represented "very poor" and 100 represented "excellent."
Timepoint [16] 0 0
Week 24 (AMB-220-E baseline)
Secondary outcome [17] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 48)
Assessment method [17] 0 0
The SGA was determined using a visual-analog scale. Subjects were asked the question, "How are you feeling today?" and were asked to draw a vertical mark on a 100-mm horizontal line in which zero represented "very poor" and 100 represented "excellent."
Timepoint [17] 0 0
24 weeks (Week 24 to Week 48)
Secondary outcome [18] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 108)
Assessment method [18] 0 0
The SGA was determined using a visual-analog scale. Subjects were asked the question, "How are you feeling today?" and were asked to draw a vertical mark on a 100-mm horizontal line in which zero represented "very poor" and 100 represented "excellent."
Timepoint [18] 0 0
84 weeks (Week 24 to Week 108)
Secondary outcome [19] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 156)
Assessment method [19] 0 0
The SGA was determined using a visual-analog scale. Subjects were asked the question, "How are you feeling today?" and were asked to draw a vertical mark on a 100-mm horizontal line in which zero represented "very poor" and 100 represented "excellent."
Timepoint [19] 0 0
132 weeks (Week 24 to Week 156)
Secondary outcome [20] 0 0
Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 204)
Assessment method [20] 0 0
The SGA was determined using a visual-analog scale. Subjects were asked the question, "How are you feeling today?" and were asked to draw a vertical mark on a 100-mm horizontal line in which zero represented "very poor" and 100 represented "excellent."
Timepoint [20] 0 0
180 weeks (Week 24 to Week 204)
Secondary outcome [21] 0 0
Time to Clinical Worsening of PAH
Assessment method [21] 0 0
Clinical worsening of PAH was defined as death, lung transplantation, hospitalization for PAH, atrial septostomy, the addition of approved prostanoid therapy, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents. Sildenafil, a type 5 phosphodiesterase (PDE-5) inhibitor, had not received regulatory approval for the treatment of PAH until late in the conduct of AMB 220 and AMB 220-E, and did not count toward clinical worsening. Results are presented as the Kaplan-Meier estimate (% probability) of not having clinical worsening after a given time.
Timepoint [21] 0 0
Week 0 (NCT00046319 baseline) to Week 360
Secondary outcome [22] 0 0
Failure-free Treatment Status
Assessment method [22] 0 0
Failure-free treatment status was defined as the time from initiation of active treatment to the first occurrence of death, lung transplantation, the addition of approved prostanoid therapy, or study withdrawal due to the addition of other clinically approved PAH therapeutic agents. Results are presented as the Kaplan-Meier estimate (% probability) of not having treatment failure after a given time.
Timepoint [22] 0 0
Week 0 (NCT00046319 baseline) to Week 360
Secondary outcome [23] 0 0
Long-term Survival
Assessment method [23] 0 0
Long-term survival was defined as the time from initiation of active treatment to death. Results are presented as the Kaplan-Meier estimate (% probability) of survival after a given time.
Timepoint [23] 0 0
Week 24 (AMB-220-E baseline) to Week 329.3

Eligibility
Key inclusion criteria
* Must have completed Visit 14/Week 24 of the NCT00046319 study.
* Women of childbearing potential must have a negative urine pregnancy test at the Screening/Enrollment Visit and agree to use a reliable double barrier method of contraception until study completion and for >=4 weeks following their final study visit.
* Must have completed the Down-titration Period of NCT00046319 prior to enrollment in AMB-220-E and will meet the following additional criteria:
* Subjects with a diagnosis of HIV must have stable disease status at the time of Screening/Enrollment.
* Must be stable on conventional therapy for PAH for >=4 weeks prior to the Screening Visit.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Chronic prostanoid therapy, or other investigational prostacyclin derivative within 4 weeks prior to the Screening Visit.
* Intravenous inotrope use within 2 weeks prior to the Screening Visit.
* Females who are pregnant or breastfeeding.
* Contraindication to treatment with an endothelin receptor antagonist (ERA).

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 2
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
1/04/2003
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2009
Sample size
Target
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

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

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00424021