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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 stycznia 2013 zaktualizowane przez: 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.

Przegląd badań

Status

Zakończony

Warunki

Interwencja / Leczenie

Szczegółowy opis

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.

Typ studiów

Interwencyjne

Zapisy (Rzeczywisty)

383

Faza

  • Faza 3

Kontakty i lokalizacje

Ta sekcja zawiera dane kontaktowe osób prowadzących badanie oraz informacje o tym, gdzie badanie jest przeprowadzane.

Lokalizacje studiów

  • Argentyna
      • Cordoba, Argentyna, X5000JHQ
        • Sanatorio Allende
      • Cordoba, Argentyna, X5016KEH
        • Hospital Privado Centro Medico de Cordoba
      • Cordoba, Argentyna, X5004 FJE
        • Hospital Italiano de Córdoba
      • Corrientes, Argentyna, W3400AMZ
        • Instituto de Cardiologia J.F. Cabral
    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentyna, C1115AAB
        • Sanatorio Otamendi
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentyna, C1280AEB
        • Hospital Britanico-Buenos Aires
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentyna, C1416A
        • Instituto del Corazon Denton A. Cooley
      • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentyna, C1437BZL
        • UAI Hosp. Universitario
      • Mar del Plata, Buenos Aires, Argentyna, 07600
        • HIGA Hospital Interzonal General de Agudos Oscar Allende
      • Munro, Buenos Aires, Argentyna, 01605
        • Clinica Independencia Munro
    • Sante Fe
      • Rosario, Sante Fe, Argentyna, 02000
        • Hospital Italiano de Rosario
  • Brazylia
      • Belo Horizonte, Brazylia, 30380-090
        • Hospital Madre Teresa
      • Porto Alegre, Brazylia, 90610-000
        • Hospital San Lucas de Pontificia Universidade Catolica
      • Porto Alegre, Brazylia, 92020-090
        • Complexo Hospitalar Sanata Casa de Porto Alegre
      • Sao Paulo, Brazylia, 05403-000
        • Hospital das Clínicas da FMUSP
      • Sao Paulo, Brazylia, 04023-062
        • Universidade do Estado de Sao Paulo - UNIFESP
    • Rio de Janeiro
      • Ilha do Fundao, Rio de Janeiro, Brazylia, 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 Clínico Universidad Católica
      • Santiago, Santiago de Chile, Chile, CP7500691
        • Instituto Nacional del Torax
  • Meksyk
    • DF
      • Mexico, DF, DF, Meksyk, 14080
        • Instituto Nacional de Cardiologia Ignacio Chavez
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Nuevo Leon, Meksyk, 64718
        • Unidad de Investigación Clinica en Medicina

Kryteria uczestnictwa

Badacze szukają osób, które pasują do określonego opisu, zwanego kryteriami kwalifikacyjnymi. Niektóre przykłady tych kryteriów to ogólny stan zdrowia danej osoby lub wcześniejsze leczenie.

Kryteria kwalifikacji

Wiek uprawniający do nauki

18 lat i starsze (Dorosły, Starszy dorosły)

Akceptuje zdrowych ochotników

Nie

Płeć kwalifikująca się do nauki

Wszystko

Opis

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.

Plan studiów

Ta sekcja zawiera szczegółowe informacje na temat planu badania, w tym sposób zaprojektowania badania i jego pomiary.

Jak projektuje się badanie?

Szczegóły projektu

  • Główny cel: Leczenie
  • Przydział: Randomizowane
  • Model interwencyjny: Przydział równoległy
  • Maskowanie: Potroić

Broń i interwencje

Grupa uczestników / Arm
Interwencja / Leczenie
Eksperymentalny: Ambrisentan
2.5, 5 or 10 mg ambrisentan
Lek: ambrisentan
2.5, 5.0 or 10.0 mg ambrisentan po, qd, long-term
Inne nazwy:
  • Letairis(TM)

Co mierzy badanie?

Podstawowe miary wyniku

Miara wyniku
Opis środka
Ramy czasowe
Frequently Reported (15% or More Overall) Adverse Events by Severity
Ramy czasowe: 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)
Ramy czasowe: 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

Miary wyników drugorzędnych

Miara wyniku
Opis środka
Ramy czasowe
Baseline Exercise Capacity as Measured by the 6-Minute Walk Distance Test
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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

Współpracownicy i badacze

Tutaj znajdziesz osoby i organizacje zaangażowane w to badanie.

Sponsor

Gilead Sciences

Śledczy

  • Krzesło do nauki: Chris Dufton, PhD, Gilead Sciences

Publikacje i pomocne linki

Osoba odpowiedzialna za wprowadzenie informacji o badaniu dobrowolnie udostępnia te publikacje. Mogą one dotyczyć wszystkiego, co jest związane z badaniem.

Publikacje ogólne

Daty zapisu na studia

Daty te śledzą postęp w przesyłaniu rekordów badań i podsumowań wyników do ClinicalTrials.gov. Zapisy badań i zgłoszone wyniki są przeglądane przez National Library of Medicine (NLM), aby upewnić się, że spełniają określone standardy kontroli jakości, zanim zostaną opublikowane na publicznej stronie internetowej.

Główne daty studiów

Rozpoczęcie studiów

1 lutego 2004

Zakończenie podstawowe (Rzeczywisty)

1 marca 2010

Ukończenie studiów (Rzeczywisty)

1 marca 2010

Daty rejestracji na studia

Pierwszy przesłany

19 grudnia 2007

Pierwszy przesłany, który spełnia kryteria kontroli jakości

19 grudnia 2007

Pierwszy wysłany (Oszacować)

21 grudnia 2007

Aktualizacje rekordów badań

Ostatnia wysłana aktualizacja (Oszacować)

15 stycznia 2013

Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości

14 stycznia 2013

Ostatnia weryfikacja

1 stycznia 2013

Więcej informacji

Terminy związane z tym badaniem

Dodatkowe istotne warunki MeSH

Inne numery identyfikacyjne badania

  • AMB-320/321-E
  • ARIES-E

Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .

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