ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis

Pulmonary Hypertension Clinical Trial

— ARTEMIS-PH  

Official title:

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects With Idiopathic Pulmonary Fibrosis and Pulmonary Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00879229
• Other study ID #: GS-US-300-0128
• Status: Terminated
• Phase: Phase 3
• First received: April 8, 2009
• Last updated: May 5, 2014
• Start date: July 2009
• Est. completion date: February 2011

Study information

• Verified date: May 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Ambrisentan is an endothelin receptor antagonist used for the treatment of pulmonary hypertension (PH). Based on research suggesting a role for endothelin-1 in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and the poor prognosis for patients with IPF who are also diagnosed with PH, this study was designed to evaluate the effectiveness and safety of ambrisentan in that patient population.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years to 80 Years

Eligibility

Selected Inclusion Criteria:

• Weight = 40 kg at screening

• Diagnosis of IPF based on modified American Thoracic Society-European Respiratory Society guidelines

• Diagnosis of PH based on the following hemodynamic requirements: mean pulmonary artery pressure (mPAP = 25 mm Hg; pulmonary vascular resistance > 240 dyne.sec/cm^5; pulmonary capillary wedge pressure or left ventricular end-diastolic pressure = 15 mm Hg

• Forced vital capacity (FVC) = 40%

• Able to walk at least 50 meters during two 6-minute walk tests

• If receiving calcium channel blockers, low-dose oral corticosteroids, immunosuppressive, cytoxic, or antifibrotic drugs dose must have been stable.

Selected Exclusion Criteria:

• Diagnosis of PH primarily due to an etiology other than IPF

• Surgical lung biopsy diagnosis other than Usual Interstitial Pneumonia

• Other known cause of interstitial lung disease

• Evidence of significant obstructive lung disease

• Recent hospitalization for an acute exacerbation of IPF

• Recent active pulmonary or upper respiratory tract infection

• Left ventricular ejection fraction < 40%

• Serum creatinine = 2.5 mg/dL

• Required hemodialysis, peritoneal dialysis, or hemofiltration

• Female subject who was pregnant or breastfeeding

• Recent treatment for PH with an endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor, or prostacyclin derivative

• Recent treatment with high dose oral corticosteroids

• Recent treatment (within 4 weeks prior to screening) with imatinib mesylate (Gleevec)

• Alanine aminotransferase or aspartate aminotransferase lab value that was greater than 1.5 x the upper limit of the normal range

• Discontinued other ERA treatment for any adverse reaction other than those associated with liver function test abnormalities

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibrosis
• Hypertension
• Hypertension, Pulmonary
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis
• Pulmonary Hypertension

Intervention

Drug:
• Ambrisentan
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily.
• Placebo
Placebo to match ambrisentan administered orally once daily.

Locations

Country	Name	City	State
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	St. Vincents Hospital	Sydney	New South Wales
Austria	Medizinische Universität Graz	Graz
Austria	Universitatsklinikum Innsbruck	Innsbruck
Austria	Medizinische Universität Wien	Vienna
Canada	Peter Loughheed Center- Calgary General Hospital	Calgary	Alberta
Canada	London Health Sciences Centre	London	Ontario
Canada	Centre Hospitalier De L'Universite de Montreal	Montreal	Quebec
Canada	Sir Mortimer B. Davis Jewish General Center	Montreal	Quebec
Canada	Centre de Pneumologie de L'Hospital Laval	Sainte foy	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
Germany	Charite-Universitatsmedizin Berlin	Berlin
Germany	Evangelische Lungenklinik Berlin	Berlin
Germany	Krankenhaus Donaustauf der LVA	Donaustauf
Germany	Universitatsklinikum Freiburg	Freiburg
Germany	Universitat Greifswald	Greifswald
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Thorax Klinik	Heidelberg
Germany	LMU Klinikum der Universitat	Munchen
Italy	Azienda Ospedaliero Universitaria	Catania
Italy	Presidio Ospedaliero G.B. Morgagni	Forli
Italy	Ospedale S.Giuseppe Fatebenefratelli	Milan
Italy	Unita Funzionale di Pneumologia e Fisiopatologia Respiratoria	Milano
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Instituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione	Palermo
Italy	Policlinico Universitario Tor Vergata	Rome
Italy	Azienda Ospedaliera Universitaria Senese	Siena
Italy	Centro delle Interstiziopatie Polmonari e Malattie Rare del Polmone	Torino
United Kingdom	Papworth Hospital NHS Foundation Trust	Cambridge
United Kingdom	University Hospital Aintree	Liverpool
United Kingdom	University College Hosptial	London
United Kingdom	Royal Hallamshire Hospital	Sheffield
United States	Albany Medical Center	Albany	New York
United States	University of Michigan Health Systems	Ann Arbor	Michigan
United States	University of Colorado Heatlh Sciences Center	Aurora	Colorado
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Beth Israel Deacones Medical Center	Boston	Massachusetts
United States	Boston University Medical Center	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Chicago	Chicago	Illinois
United States	The Lindner Center for Research & Education at The Christ Hospital	Cincinnati	Ohio
United States	Bay Area Chest Physicians	Clearwater	Florida
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals of Cleveland Case Western	Cleveland	Ohio
United States	Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern	Dallas	Texas
United States	University of California Davis	Davis	California
United States	Atlanta Institute for Medical Research	Decatur	Georgia
United States	Duke University Medical Center	Durham	North Carolina
United States	Providence Everett Medical Center	Everett	Washington
United States	Inova Heart Institiute and Vascular Institute	Falls Church	Virginia
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Dartmouth Medical School	Lebanon	New Hampshire
United States	David Geffen School of Medicine UCLA	Los Angeles	California
United States	Kentuckiana Pulmonary Association	Louisville	Kentucky
United States	University of Miami Medical Center	Miami	Florida
United States	Winthrop University Hospital	Mineola	New York
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	North Shore Health System	New Hyde Park	New York
United States	Columbia University	New York	New York
United States	Mount Sinai School of Medicine	New York	New York
United States	Creighton University Center for Allergy & Asthma	Omaha	Nebraska
United States	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	Temple University School of Medicine	Philadelphia	Pennsylvania
United States	Alleghany General Hospital	Pittsburgh	Pennsylvania
United States	University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania
United States	Maine Medical Center	Portland	Maine
United States	Virginia Commonwealth University Health System	Richmond	Virginia
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	University of Utah	Salt Lake City	Utah
United States	University of California San Diego Medical Center	San Diego	California
United States	University of California at San Francisco	San Francisco	California
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Suncoast Lung Center	Sarasota	Florida
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Washington University	St Louis	Missouri
United States	Stanford University	Stanford	California
United States	Cleveland Clinic Florida	Weston	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Canada,  Germany,  Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Six-minute Walk Distance (6MWD).	The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.	Baseline to Week 16	No
Secondary	Long-term Survival	Long-term survival was assessed as a Kaplan-Meier (KM) estimate of the percent probability of survival, with censoring at Week 48.	Week 48	No
Secondary	Transition Dyspnea Index (TDI)	The change in TDI at Week 16 (end of blinded treatment) was evaluated. TDI measures the change from the baseline characteristic "Baseline Dyspnea Index." The TDI range is -9 to +9 (worst to best; 0 = no change).	Baseline to Week 16	No
Secondary	Change From Baseline in WHO Functional Class	WHO functional class rates severity of pulmonary hypertension, with 4 categories on a scale of 1 to 4 with the worst category being 4. Change is represented as an increase ("+1: Improved"), decrease ("-1: Deteriorated"), or no change ("0: No change") on the scale.	Baseline to Week 16	No
Secondary	Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted	FVC is a pulmonary function test, and is defined as the volume of air that can forcibly be blown out after taking a full breath. FVC% predicted is defined as FVC% of the patient divided by the average FVC% in the population for any person of similar age, sex and body composition.	Baseline to Week 16	No
Secondary	Change From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP)	Assessment of the the level of the amino acid fragment NT-proBNP is used to establish prognosis in cardiovascular disease.	Baseline to Week 16	No
Secondary	Change From Baseline in the Borg Dyspnea Index (BORG) Immediately Following Exercise	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 to Week 16	No
Secondary	Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted	DLCO is a pulmonary function test, and measures the partial pressure difference between inspired and expired carbon monoxide. DLCO% predicted is defined as DLCO% of the patient divided by the average DLCO% in the population for any person of similar age, sex and body composition.	Baseline to Week 16	No
Secondary	Change in Quality of Life (QOL) Score as Assessed by the Short-Form 36® (SF-36)	Each SF-36 score is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. An increase in score indicates an improvement in health state.	Baseline to Week 16	No
Secondary	Change in QOL Score as Assessed by the St. George's Respiratory Questionnaire (SRGQ)	The SRGQ is designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Patients respond to questions about symptoms (frequency & severity) and impact components (social functioning and psychological disturbances resulting from airways disease). Scores range from 0 to 100, with higher scores indicating more limitations.	Baseline to Week 16	No