Phase 2 Extension Study of Ambrisentan in Pulmonary Arterial Hypertension

Pulmonary Hypertension Clinical Trial

Official title:

An Open-Label, Long-Term Study of Ambrisentan in Pulmonary Hypertension Subjects Having Completed Myogen Study AMB-220

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00424021
• Other study ID #: AMB-220-E
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2007
• Last updated: December 21, 2011
• Start date: April 2003
• Est. completion date: December 2009

Study information

• Verified date: December 2011
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

AMB-220-E is an international, multicenter, open-label study examining the long-term safety of ambrisentan (BSF 208075) in subjects who have previously completed Myogen study NCT00046319, "A Phase II, Randomized, Double-Blind, Dose-Controlled, Dose-Ranging, Multicenter Study of BSF 208075 Evaluating Exercise Capacity in Subjects with Moderate to Severe Pulmonary Arterial Hypertension".

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Pulmonary Hypertension

Intervention

Drug:
• ambrisentan
1, 2.5, 5, and 10 mg ambrisentan given orally once daily

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Week 24 (AMB-220-E baseline) to Week 334	Yes
Primary	Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Moderate Severity During Long-term Ambrisentan Exposure	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.	Week 24 (AMB-220-E baseline) to Week 329.3	Yes
Primary	Number of Participants With PAH Who Completed the Phase II NCT00046319 Study and Who Experienced AEs of Mild Severity During Long-term Ambrisentan Exposure	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.	Week 24 (AMB-220-E baseline) to Week 329.3	Yes
Secondary	Baseline Measurement in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (Baseline [Week 24])	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).	Week 24 (AMB-220-E baseline)	No
Secondary	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)	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).	24 weeks (Week 24 to Week 48)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (LOCF) (Week 108)	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).	84 weeks (Week 24 to Week 108)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (LOCF) (Week 156)	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).	132 weeks (Week 24 to Week 156)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the 6-minute Walk Test (6MWT) Distance (LOCF) (Week 204)	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).	180 weeks (Week 24 to Week 204)	No
Secondary	Baseline Measurement in Exercise Capacity as Measured by the Borg Dyspnea Index (BDI) (Baseline [Week 24])	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).	Week 24 (AMB-220-E baseline)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 48)	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).	24 weeks (Week 24 to Week 48)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 108)	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).	84 weeks (Week 24 to Week 108)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 156)	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).	132 weeks (Week 24 to Week 156)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the BDI (LOCF) (Week 204)	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).	180 weeks (Week 24 to Week 204)	No
Secondary	Baseline Measurement in Exercise Capacity as Measured by the World Health Organization (WHO) Functional Classification (Baseline [Week 24])	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.	Week 24 (AMB-220-E baseline)	No
Secondary	Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 24 Weeks of Treatment in AMB-220-E	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.	24 weeks (Week 24 [baseline of AMB-220-E] to Week 48)	No
Secondary	Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 84 Weeks of Treatment in AMB-220-E	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.	84 weeks (Week 24 of NCT00046319 to Week 108)	No
Secondary	Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 132 Weeks of Treatment in AMB-220-E	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.	132 weeks (Week 24 of NCT00046319 to Week 156)	No
Secondary	Exercise Capacity as Measured by the WHO Functional Classification (LOCF) After 180 Weeks of Treatment in AMB-220-E	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.	180 weeks (Week 24 of NCT00046319 to Week 204)	No
Secondary	Baseline Measurement in Exercise Capacity as Measured by the Subject Global Assessment (SGA) (Baseline [Week 24])	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."	Week 24 (AMB-220-E baseline)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 48)	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."	24 weeks (Week 24 to Week 48)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 108)	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."	84 weeks (Week 24 to Week 108)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 156)	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."	132 weeks (Week 24 to Week 156)	No
Secondary	Change From Baseline (Week 24 of NCT00046319) in Exercise Capacity as Measured by the SGA (LOCF) (Week 204)	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."	180 weeks (Week 24 to Week 204)	No
Secondary	Time to Clinical Worsening of PAH	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.	Week 0 (NCT00046319 baseline) to Week 360	No
Secondary	Failure-free Treatment Status	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.	Week 0 (NCT00046319 baseline) to Week 360	No
Secondary	Long-term Survival	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.	Week 24 (AMB-220-E baseline) to Week 329.3	No

External Links

•   Pulmonary Hypertension Association