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

14 gennaio 2013 aggiornato da: Gilead Sciences
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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Tipo di studio

Interventistico

Iscrizione (Effettivo)

383

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Argentina
      • Cordoba, Argentina, X5000JHQ
        • Sanatorio Allende
      • Cordoba, Argentina, X5016KEH
        • Hospital Privado Centro Médico de Córdoba
      • Cordoba, Argentina, X5004 FJE
        • Hospital Italiano de Cordoba
      • Corrientes, Argentina, W3400AMZ
        • Instituto de Cardiologia J.F. Cabral
    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1115AAB
        • Sanatorio Otamendi
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1280AEB
        • Hospital Britanico-Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1416A
        • Instituto del Corazon Denton A. Cooley
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1437BZL
        • UAI Hosp. Universitario
      • Mar del Plata, Buenos Aires, Argentina, 07600
        • HIGA Hospital Interzonal General de Agudos Oscar Allende
      • Munro, Buenos Aires, Argentina, 01605
        • Clinica Independencia Munro
    • Sante Fe
      • Rosario, Sante Fe, Argentina, 02000
        • Hospital Italiano de Rosario
  • Brasile
      • Belo Horizonte, Brasile, 30380-090
        • Hospital Madre Teresa
      • Porto Alegre, Brasile, 90610-000
        • Hospital San Lucas de Pontificia Universidade Catolica
      • Porto Alegre, Brasile, 92020-090
        • Complexo Hospitalar Sanata Casa de Porto Alegre
      • Sao Paulo, Brasile, 05403-000
        • Hospital das Clinicas da FMUSP
      • Sao Paulo, Brasile, 04023-062
        • Universidade do Estado de Sao Paulo - UNIFESP
    • Rio de Janeiro
      • Ilha do Fundao, Rio de Janeiro, Brasile, 21941-590
        • Hospital Universitario Clementino Fraga Filho
  • Chile
    • Santiago de Chile
      • Santiago, Santiago de Chile, Chile, CP 8330024
        • Hospital San Juan de Dios
      • Santiago, Santiago de Chile, Chile, CP 8350488
        • Hospital Clinico Universidad Catolica
      • Santiago, Santiago de Chile, Chile, CP7500691
        • Instituto Nacional del Tórax
  • Messico
    • DF
      • Mexico, DF, DF, Messico, 14080
        • Instituto Nacional de Cardiologia Ignacio Chavez
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Nuevo Leon, Messico, 64718
        • Unidad De Investigacion Clinica en Medicina

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Triplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Ambrisentan
2.5, 5 or 10 mg ambrisentan
Droga: ambrisentan
2.5, 5.0 or 10.0 mg ambrisentan po, qd, long-term
Altri nomi:
  • Letairis(TM)

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Frequently Reported (15% or More Overall) Adverse Events by Severity
Lasso di tempo: Baseline to Week 295
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).
Baseline to Week 295
Serum Aminotransferases Relative to the Upper Limit of the Normal Range (ULN)
Lasso di tempo: Baseline to Week 295
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.
Baseline to Week 295

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Baseline Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Lasso di tempo: Baseline
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.).
Baseline
Change From Baseline to Week 24 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Lasso di tempo: Baseline to Week 24
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.
Baseline to Week 24
Change From Baseline to Week 48 (Year 1) in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Lasso di tempo: Baseline to Week 48
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.
Baseline to Week 48
Change From Baseline to Year 2 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Lasso di tempo: Baseline to Year 2
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.
Baseline to Year 2
Change From Baseline to Year 3 in Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Lasso di tempo: Baseline to Year 3
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 to Year 3
Baseline Borg Dyspnea Index
Lasso di tempo: Baseline
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
Change From Baseline to Year 1 in Borg Dyspnea Index
Lasso di tempo: Baseline to Year 1
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.
Baseline to Year 1
Change From Baseline to Year 2 in Borg Dyspnea Index
Lasso di tempo: Baseline to Year 2
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 to Year 2
Change From Baseline to Year 3 in Borg Dyspnea Index
Lasso di tempo: Baseline to Year 3
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 to Year 3
Baseline World Health Organization (WHO) Functional Class
Lasso di tempo: Baseline
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
Change From Baseline to Year 1 in World Health Organization (WHO) Functional Class
Lasso di tempo: Baseline to Year 1
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 to Year 1
Change From Baseline to Year 2 in World Health Organization (WHO) Functional Class
Lasso di tempo: Baseline to Year 2
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 to Year 2
Change From Baseline to Year 3 in World Health Organization (WHO) Functional Class
Lasso di tempo: Baseline to Year 3
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 to Year 3
Baseline SF-36 Health Survey Scales for the Combined Ambrisentan Group
Lasso di tempo: Baseline
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.
Baseline
Change From Baseline to Week 12 in SF-36 Health Survey Scales for the Combined Ambrisentan Group
Lasso di tempo: Baseline to Week 12
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.
Baseline to Week 12
Change From Baseline to Week 24 in SF-36 Health Survey Scales for the Combined Ambrisentan Group
Lasso di tempo: Baseline to Week 24
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.
Baseline to Week 24
Change From Baseline to Week 36 in SF-36 Health Survey Scales for the Combined Ambrisentan Group
Lasso di tempo: Baseline to Week 36
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.
Baseline to Week 36
Percentage of Participants With No Clinical Worsening of PAH
Lasso di tempo: Baseline to Year 3
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.
Baseline to Year 3
Percentage of Participants With Failure-Free Treatment Status
Lasso di tempo: Baseline to Year 4
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.
Baseline to Year 4
Long-term Survival
Lasso di tempo: Baseline to Year 4
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.
Baseline to Year 4

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Gilead Sciences

Investigatori

  • Cattedra di studio: Chris Dufton, PhD, Gilead Sciences

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 febbraio 2004

Completamento primario (Effettivo)

1 marzo 2010

Completamento dello studio (Effettivo)

1 marzo 2010

Date di iscrizione allo studio

Primo inviato

19 dicembre 2007

Primo inviato che soddisfa i criteri di controllo qualità

19 dicembre 2007

Primo Inserito (Stima)

21 dicembre 2007

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

15 gennaio 2013

Ultimo aggiornamento inviato che soddisfa i criteri QC

14 gennaio 2013

Ultimo verificato

1 gennaio 2013

Maggiori informazioni

Termini relativi a questo studio

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • AMB-320/321-E
  • ARIES-E

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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