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A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 (NCT00423748) or AMB-321 (NCT00423202)

Primary Purpose

Pulmonary Arterial Hypertension

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

About this trial

This is an interventional treatment trial for Pulmonary Arterial Hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Subject must have completed Week 12 of AMB-320 (NCT00423748) or AMB-321 (NCT00423202) or must have received placebo during AMB-320 (NCT00423748) or AMB-321 (NCT00423202) and met two or more early escape criteria;
  2. Subject must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent form and must sign the form prior to the initiation of any study procedures.
  3. Female subject of childbearing potential must agree to use two reliable methods of contraception until study completion and for at least four weeks following their final study visit. Reliable methods include: birth control pills/implants/injections, intrauterine devices (IUDs), spermicide, diaphragms, or condoms.

Exclusion Criteria:

  • Subjects must have met the exclusion criteria of the AMB-320 (NCT00423748) and AMB-321 (NCT00423202)studies. In addition, a subject who meets any one of the following criteria is ineligible for participation in the study:

    1. Subject receiving bosentan, sildenafil, or iv inotropes at any time within four weeks prior to the AMB-320/321-E Screening/Randomization Visit;
    2. Subject receiving chronic prostanoid therapy (epoprostenol, treprostinil, iloprost, beraprost, or any other investigational prostacyclin derivative) within four weeks prior to the AMB-320/321-E Screening/RandomizationVisit;
    3. Female subject who is pregnant or breastfeeding;
    4. Subject with cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject;
    5. Subject who has demonstrated noncompliance with previous medical regimens;
    6. Subject who has a recent history of abusing alcohol or illicit drugs;
    7. Subject who has participated in a clinical study involving another investigational drug or device at any time within four weeks prior to the AMB-320/321-E Screening/Randomization Visit.

Sites / Locations

  • Sanatorio Otamendi
  • Hospital Britanico-Buenos Aires
  • Instituto del Corazon Denton A. Cooley
  • UAI Hosp. Universitario
  • HIGA Hospital Interzonal General de Agudos Oscar Allende
  • Clinica Independencia Munro
  • Hospital Italiano de Rosario
  • Sanatorio Allende
  • Hospital Italiano de Cordoba
  • Hospital Privado Centro Medico de Cordoba
  • Instituto de Cardiologia J.F. Cabral
  • Hospital Universitario Clementino Fraga Filho
  • Hospital Madre Teresa
  • Hospital San Lucas de Pontificia Universidade Catolica
  • Complexo Hospitalar Sanata Casa de Porto Alegre
  • Universidade do Estado de Sao Paulo - UNIFESP
  • Hospital das Clinicas da FMUSP
  • Hospital San Juan de Dios
  • Hospital Clinico Universidad Catolica
  • Instituto Nacional del Torax
  • Instituto Nacional de Cardiologia Ignacio Chavez
  • Unidad De Investigacion Clinica en Medicina

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ambrisentan

Arm Description

2.5, 5 or 10 mg ambrisentan

Outcomes

Primary Outcome Measures

Frequently Reported (15% or More Overall) Adverse Events by Severity
The primary endpoint of this study is the incidence and severity of adverse events associated with long-term exposure to AMB in participants with PAH. The most frequently occurring adverse events (occurring in 15% or more of the participants in the combined group) are presented, by severity, that began after entering this extension study. Adverse events that were serious are included. Adverse events are coded according to the Medical Dictionary for Regulatory Activities (MedDRA) Version 6.1 and are presented by MedDRA preferred term. Severity was graded as follows: mild (AE did not interfere with routine activities; subject may have experienced slight discomfort), moderate (AE interfered with routine activities; subject may have experienced significant discomfort), and severe (AE made it impossible to perform routine activities; subject may have experienced intolerable discomfort or pain).
Serum Aminotransferases Relative to the Upper Limit of the Normal Range (ULN)
The number of participants with serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) falling into the following categories: >3.0 and </= 5.0 x ULN, >5.0 and </= 8.0 x ULN, and >8.0 x ULN. Includes the highest value per participant across all visits as well as values from early termination visits.

Secondary Outcome Measures

Baseline Exercise Capacity as Measured by the 6-Minute Walk Distance Test
The 6-minute walk distance (6MWD) test 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.).
Change From Baseline to Week 24 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
The 6-minute walk distance (6MWD) test 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.). Missing values were imputed using LOCF method based on post-baseline observations. Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving ambrisentan in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Change From Baseline to Week 48 (Year 1) in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
The 6-minute walk distance (6MWD) test 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.). The last-observation-carried-forward (LOCF) imputation method was used. Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Change From Baseline to Year 2 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
The 6-minute walk distance (6MWD) test 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.). The last-observation-carried-forward (LOCF) imputation method was used. Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Change From Baseline to Year 3 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.). The last-observation-carried-forward (LOCF) imputation method was used. Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Baseline Borg Dyspnea Index
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Change From Baseline to Year 1 in Borg Dyspnea Index
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness). Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving ambrisentan in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Change From Baseline to Year 2 in Borg Dyspnea Index
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness). Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Change From Baseline to Year 3 in Borg Dyspnea Index
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness). Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Baseline World Health Organization (WHO) Functional Class
WHO 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 possible at rest.
Change From Baseline to Year 1 in World Health Organization (WHO) Functional Class
WHO 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 possible at rest.
Change From Baseline to Year 2 in World Health Organization (WHO) Functional Class
WHO 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 possible at rest.
Change From Baseline to Year 3 in World Health Organization (WHO) Functional Class
WHO 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 possible at rest.
Baseline SF-36 Health Survey Scales for the Combined Ambrisentan Group
The 8 scales of the SF-36 Health Survey measured included physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, and the summary measures included physical health and mental health. Scores for each scale are transformed and the transformed scores range from 0 (worst health) to 100 (best health). 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.
Change From Baseline to Week 12 in SF-36 Health Survey Scales for the Combined Ambrisentan Group
The 8 scales of the SF-36 Health Survey measured included physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, and the summary measures included physical health and mental health. Scores for each scale are transformed and the transformed scores range from 0 (worst health) to 100 (best health). The scores are then standardized with the 1998 General US population mean and SD. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.
Change From Baseline to Week 24 in SF-36 Health Survey Scales for the Combined Ambrisentan Group
The 8 scales of the SF-36 Health Survey measured included physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, and the summary measures included physical health and mental health. Scores for each scale are transformed and the transformed scores range from 0 (worst health) to 100 (best health). The scores are then standardized with the 1998 General US population mean and SD. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.
Change From Baseline to Week 36 in SF-36 Health Survey Scales for the Combined Ambrisentan Group
The 8 scales of the SF-36 Health Survey measured included physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, and the summary measures included physical health and mental health. Scores for each scale are transformed and the transformed scores range from 0 (worst health) to 100 (best health). The scores are then standardized with the 1998 General US population mean and SD. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.
Percentage of Participants With No Clinical Worsening of PAH
Clinical worsening of PAH was defined as the time from randomization to ambrisentan therapy to the first occurrence of death, lung transplantation, hospitalization for PAH, atrial septostomy, addition of approved prostanoid therapy, study withdrawal due to the addition of other clinically approved PAH therapeutics, or study withdrawal due to 2 or more early escape criteria (for subjects randomized to AMB in NCT00423748 or NCT00423202). Results are presented as the Kaplan-Meier estimate (% probability) of not having clinical worsening after a given time.
Percentage of Participants With Failure-Free Treatment Status
Treatment failure was defined as the time from randomization to ambrisentan therapy to the first occurrence of death, lung transplantation, addition of approved prostanoid therapy, study withdrawal due to the addition of other clinically approved PAH therapeutics, or study withdrawal due to 2 or more early escape criteria (for subjects randomized to ambrisentan in NCT00423748 or NCT00423202). Results are presented as the Kaplan-Meier estimate (% probability) of not having treatment failure after a given time.
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.

Full Information

First Posted
December 19, 2007
Last Updated
January 14, 2013
Sponsor
Gilead Sciences
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1. Study Identification

Unique Protocol Identification Number
NCT00578786
Brief Title
A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 (NCT00423748) or AMB-321 (NCT00423202)
Official Title
A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 (NCT00423748) or AMB-321 (NCT00423202)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
March 2010 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
AMB-320/321-E was designed to provide long-term, controlled monitoring of pulmonary arterial hypertension (PAH) patients treated with ambrisentan (AMB) in order to properly define the adverse event profile associated with this endothelin receptor antagonist (ERA), including the incidence and severity of elevated serum liver function tests (LFTs). In addition, this study continued the efficacy assessments of the previous studies, examined long-term AMB treatment success, and compared long-term survival of subjects treated with AMB to the NIH registry of patients with PAH.
Detailed Description
AMB-320 (ARIES-1; NCT00423748) and AMB-321 (ARIES-2; NCT00423202) were 12-week, Phase 3, randomized, double-blind, placebo-controlled, multicenter, efficacy studies of AMB in subjects with PAH. The objectives of these studies were to determine the effect of three doses of AMB (2.5, 5.0, and 10.0 mg) on exercise capacity, as well as several clinical measures of PAH. The current study (NCT00578786) was unblinded (by design) prior to completion. The ARIES studies were identical except for the dose groups assessed and the geographic locations where the studies were conducted. Both studies evaluated placebo and 5.0-mg AMB dose groups; however, AMB-320 (NCT00423748) also examined an AMB dose of 10.0 mg, while AMB-321 (NCT00423202) included an AMB dose of 2.5 mg. AMB-320/321-E was an optional study for subjects who had participated in AMB-320 (NCT00423748) or AMB-321 (NCT00423202) that allowed continued long-term treatment with AMB.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Arterial Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
383 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Ambrisentan
Arm Type
Experimental
Arm Description
2.5, 5 or 10 mg ambrisentan
Intervention Type
Drug
Intervention Name(s)
ambrisentan
Other Intervention Name(s)
Letairis(TM)
Intervention Description
2.5, 5.0 or 10.0 mg ambrisentan po, qd, long-term
Primary Outcome Measure Information:
Title
Frequently Reported (15% or More Overall) Adverse Events by Severity
Description
The primary endpoint of this study is the incidence and severity of adverse events associated with long-term exposure to AMB in participants with PAH. The most frequently occurring adverse events (occurring in 15% or more of the participants in the combined group) are presented, by severity, that began after entering this extension study. Adverse events that were serious are included. Adverse events are coded according to the Medical Dictionary for Regulatory Activities (MedDRA) Version 6.1 and are presented by MedDRA preferred term. Severity was graded as follows: mild (AE did not interfere with routine activities; subject may have experienced slight discomfort), moderate (AE interfered with routine activities; subject may have experienced significant discomfort), and severe (AE made it impossible to perform routine activities; subject may have experienced intolerable discomfort or pain).
Time Frame
Baseline to Week 295
Title
Serum Aminotransferases Relative to the Upper Limit of the Normal Range (ULN)
Description
The number of participants with serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) falling into the following categories: >3.0 and </= 5.0 x ULN, >5.0 and </= 8.0 x ULN, and >8.0 x ULN. Includes the highest value per participant across all visits as well as values from early termination visits.
Time Frame
Baseline to Week 295
Secondary Outcome Measure Information:
Title
Baseline Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Description
The 6-minute walk distance (6MWD) test 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.).
Time Frame
Baseline
Title
Change From Baseline to Week 24 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Description
The 6-minute walk distance (6MWD) test 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.). Missing values were imputed using LOCF method based on post-baseline observations. Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving ambrisentan in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Time Frame
Baseline to Week 24
Title
Change From Baseline to Week 48 (Year 1) in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Description
The 6-minute walk distance (6MWD) test 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.). The last-observation-carried-forward (LOCF) imputation method was used. Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Time Frame
Baseline to Week 48
Title
Change From Baseline to Year 2 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Description
The 6-minute walk distance (6MWD) test 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.). The last-observation-carried-forward (LOCF) imputation method was used. Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Time Frame
Baseline to Year 2
Title
Change From Baseline to Year 3 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Description
Thoracic Society guidelines (ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 2002; 166(1):111-117.). The last-observation-carried-forward (LOCF) imputation method was used. Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Time Frame
Baseline to Year 3
Title
Baseline Borg Dyspnea Index
Description
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness).
Time Frame
Baseline
Title
Change From Baseline to Year 1 in Borg Dyspnea Index
Description
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness). Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving ambrisentan in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Time Frame
Baseline to Year 1
Title
Change From Baseline to Year 2 in Borg Dyspnea Index
Description
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness). Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Time Frame
Baseline to Year 2
Title
Change From Baseline to Year 3 in Borg Dyspnea Index
Description
Borg Dyspnea Index is a measure of perceived shortness of breath: 0 units on a scale (none) to 10 units on a scale (maximum breathlessness). Baseline (BL) values from the screening/randomization visit of the 2 prior studies defined the BL of this long-term analysis for those receiving AMB in the prior studies. The Screening/Randomization Visit of the present study was the BL for subjects receiving placebo in the prior studies.
Time Frame
Baseline to Year 3
Title
Baseline World Health Organization (WHO) Functional Class
Description
WHO 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 possible at rest.
Time Frame
Baseline
Title
Change From Baseline to Year 1 in World Health Organization (WHO) Functional Class
Description
WHO 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 possible at rest.
Time Frame
Baseline to Year 1
Title
Change From Baseline to Year 2 in World Health Organization (WHO) Functional Class
Description
WHO 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 possible at rest.
Time Frame
Baseline to Year 2
Title
Change From Baseline to Year 3 in World Health Organization (WHO) Functional Class
Description
WHO 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 possible at rest.
Time Frame
Baseline to Year 3
Title
Baseline SF-36 Health Survey Scales for the Combined Ambrisentan Group
Description
The 8 scales of the SF-36 Health Survey measured included physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, and the summary measures included physical health and mental health. Scores for each scale are transformed and the transformed scores range from 0 (worst health) to 100 (best health). 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.
Time Frame
Baseline
Title
Change From Baseline to Week 12 in SF-36 Health Survey Scales for the Combined Ambrisentan Group
Description
The 8 scales of the SF-36 Health Survey measured included physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, and the summary measures included physical health and mental health. Scores for each scale are transformed and the transformed scores range from 0 (worst health) to 100 (best health). The scores are then standardized with the 1998 General US population mean and SD. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.
Time Frame
Baseline to Week 12
Title
Change From Baseline to Week 24 in SF-36 Health Survey Scales for the Combined Ambrisentan Group
Description
The 8 scales of the SF-36 Health Survey measured included physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, and the summary measures included physical health and mental health. Scores for each scale are transformed and the transformed scores range from 0 (worst health) to 100 (best health). The scores are then standardized with the 1998 General US population mean and SD. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.
Time Frame
Baseline to Week 24
Title
Change From Baseline to Week 36 in SF-36 Health Survey Scales for the Combined Ambrisentan Group
Description
The 8 scales of the SF-36 Health Survey measured included physical functioning, role physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health, and the summary measures included physical health and mental health. Scores for each scale are transformed and the transformed scores range from 0 (worst health) to 100 (best health). The scores are then standardized with the 1998 General US population mean and SD. Finally, the scores are transformed to the norm-based scoring with a mean of 50 and SD of 10.
Time Frame
Baseline to Week 36
Title
Percentage of Participants With No Clinical Worsening of PAH
Description
Clinical worsening of PAH was defined as the time from randomization to ambrisentan therapy to the first occurrence of death, lung transplantation, hospitalization for PAH, atrial septostomy, addition of approved prostanoid therapy, study withdrawal due to the addition of other clinically approved PAH therapeutics, or study withdrawal due to 2 or more early escape criteria (for subjects randomized to AMB in NCT00423748 or NCT00423202). Results are presented as the Kaplan-Meier estimate (% probability) of not having clinical worsening after a given time.
Time Frame
Baseline to Year 3
Title
Percentage of Participants With Failure-Free Treatment Status
Description
Treatment failure was defined as the time from randomization to ambrisentan therapy to the first occurrence of death, lung transplantation, addition of approved prostanoid therapy, study withdrawal due to the addition of other clinically approved PAH therapeutics, or study withdrawal due to 2 or more early escape criteria (for subjects randomized to ambrisentan in NCT00423748 or NCT00423202). Results are presented as the Kaplan-Meier estimate (% probability) of not having treatment failure after a given time.
Time Frame
Baseline to Year 4
Title
Long-term Survival
Description
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.
Time Frame
Baseline to Year 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Subject must have completed Week 12 of AMB-320 (NCT00423748) or AMB-321 (NCT00423202) or must have received placebo during AMB-320 (NCT00423748) or AMB-321 (NCT00423202) and met two or more early escape criteria; Subject must be competent to understand the information given in the Institutional Review Board (IRB) or Independent Ethics Committee (IEC) approved informed consent form and must sign the form prior to the initiation of any study procedures. Female subject of childbearing potential must agree to use two reliable methods of contraception until study completion and for at least four weeks following their final study visit. Reliable methods include: birth control pills/implants/injections, intrauterine devices (IUDs), spermicide, diaphragms, or condoms. Exclusion Criteria: Subjects must have met the exclusion criteria of the AMB-320 (NCT00423748) and AMB-321 (NCT00423202)studies. In addition, a subject who meets any one of the following criteria is ineligible for participation in the study: Subject receiving bosentan, sildenafil, or iv inotropes at any time within four weeks prior to the AMB-320/321-E Screening/Randomization Visit; Subject receiving chronic prostanoid therapy (epoprostenol, treprostinil, iloprost, beraprost, or any other investigational prostacyclin derivative) within four weeks prior to the AMB-320/321-E Screening/RandomizationVisit; Female subject who is pregnant or breastfeeding; Subject with cardiovascular, liver, renal, hematologic, gastrointestinal, immunologic, endocrine, metabolic, or central nervous system disease that, in the opinion of the Investigator, may adversely affect the safety of the subject and/or efficacy of the study drug or severely limit the lifespan of the subject; Subject who has demonstrated noncompliance with previous medical regimens; Subject who has a recent history of abusing alcohol or illicit drugs; Subject who has participated in a clinical study involving another investigational drug or device at any time within four weeks prior to the AMB-320/321-E Screening/Randomization Visit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chris Dufton, PhD
Organizational Affiliation
Gilead Sciences
Official's Role
Study Chair
Facility Information:
Facility Name
Sanatorio Otamendi
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1115AAB
Country
Argentina
Facility Name
Hospital Britanico-Buenos Aires
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1280AEB
Country
Argentina
Facility Name
Instituto del Corazon Denton A. Cooley
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1416A
Country
Argentina
Facility Name
UAI Hosp. Universitario
City
Ciudad Autonoma de Buenos Aires
State/Province
Buenos Aires
ZIP/Postal Code
C1437BZL
Country
Argentina
Facility Name
HIGA Hospital Interzonal General de Agudos Oscar Allende
City
Mar del Plata
State/Province
Buenos Aires
ZIP/Postal Code
07600
Country
Argentina
Facility Name
Clinica Independencia Munro
City
Munro
State/Province
Buenos Aires
ZIP/Postal Code
01605
Country
Argentina
Facility Name
Hospital Italiano de Rosario
City
Rosario
State/Province
Sante Fe
ZIP/Postal Code
02000
Country
Argentina
Facility Name
Sanatorio Allende
City
Cordoba
ZIP/Postal Code
X5000JHQ
Country
Argentina
Facility Name
Hospital Italiano de Cordoba
City
Cordoba
ZIP/Postal Code
X5004 FJE
Country
Argentina
Facility Name
Hospital Privado Centro Medico de Cordoba
City
Cordoba
ZIP/Postal Code
X5016KEH
Country
Argentina
Facility Name
Instituto de Cardiologia J.F. Cabral
City
Corrientes
ZIP/Postal Code
W3400AMZ
Country
Argentina
Facility Name
Hospital Universitario Clementino Fraga Filho
City
Ilha do Fundao
State/Province
Rio de Janeiro
ZIP/Postal Code
21941-590
Country
Brazil
Facility Name
Hospital Madre Teresa
City
Belo Horizonte
ZIP/Postal Code
30380-090
Country
Brazil
Facility Name
Hospital San Lucas de Pontificia Universidade Catolica
City
Porto Alegre
ZIP/Postal Code
90610-000
Country
Brazil
Facility Name
Complexo Hospitalar Sanata Casa de Porto Alegre
City
Porto Alegre
ZIP/Postal Code
92020-090
Country
Brazil
Facility Name
Universidade do Estado de Sao Paulo - UNIFESP
City
Sao Paulo
ZIP/Postal Code
04023-062
Country
Brazil
Facility Name
Hospital das Clinicas da FMUSP
City
Sao Paulo
ZIP/Postal Code
05403-000
Country
Brazil
Facility Name
Hospital San Juan de Dios
City
Santiago
State/Province
Santiago de Chile
ZIP/Postal Code
CP 8330024
Country
Chile
Facility Name
Hospital Clinico Universidad Catolica
City
Santiago
State/Province
Santiago de Chile
ZIP/Postal Code
CP 8350488
Country
Chile
Facility Name
Instituto Nacional del Torax
City
Santiago
State/Province
Santiago de Chile
ZIP/Postal Code
CP7500691
Country
Chile
Facility Name
Instituto Nacional de Cardiologia Ignacio Chavez
City
Mexico, DF
State/Province
DF
ZIP/Postal Code
14080
Country
Mexico
Facility Name
Unidad De Investigacion Clinica en Medicina
City
Monterrey, Nuevo Leon
State/Province
Nuevo Leon
ZIP/Postal Code
64718
Country
Mexico

12. IPD Sharing Statement

Citations:
PubMed Identifier
19909879
Citation
Oudiz RJ, Galie N, Olschewski H, Torres F, Frost A, Ghofrani HA, Badesch DB, McGoon MD, McLaughlin VV, Roecker EB, Harrison BC, Despain D, Dufton C, Rubin LJ; ARIES Study Group. Long-term ambrisentan therapy for the treatment of pulmonary arterial hypertension. J Am Coll Cardiol. 2009 Nov 17;54(21):1971-81. doi: 10.1016/j.jacc.2009.07.033.
Results Reference
derived

Learn more about this trial

A Long Term Study of Ambrisentan in Pulmonary Arterial Hypertension Subjects Having Completed AMB-320 (NCT00423748) or AMB-321 (NCT00423202)

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