(ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF

This study has been terminated.
(Lack of efficacy)
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00768300
First received: October 7, 2008
Last updated: February 27, 2014
Last verified: February 2014
  Purpose

The ARTEMIS-IPF study was conducted to determine if ambrisentan was effective in delaying disease progression and death in participants with idiopathic pulmonary fibrosis (IPF), to evaluate its safety, and to evaluate its effect on development of pulmonary hypertension, quality of life, and dyspnea (shortness of breath) symptoms in this participant population. Participants were randomized in a 2:1 ratio to receive ambrisentan or placebo, respectively. Participation in the study was to be up to 4 years, depending on how long it would take to enroll participants and observe study events. After randomization, visits to the clinic took place every 3 months, and laboratory procedures were performed every month.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
Drug: Ambrisentan
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: ARTEMIS-IPF: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group, Event Driven Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects With Early Idiopathic Pulmonary Fibrosis (IPF)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Time to Death or Disease (IPF) Progression. [ Time Frame: Up to 48 months ] [ Designated as safety issue: No ]

    The median time to death or disease progression was based on Kaplan-Meier (KM) estimates of pooling over strata, and was defined as the first occurrence of any of the following:

    • Either 1) a decrease of ≥ 10% in FVC (L) and a decrease of ≥ 5% in diffuse lung capacity for carbon monoxide (DLCO) (ml/min/mmHg), or 2) a decrease of ≥ 5% in FVC (L) and a decrease of ≥ 15% in DLCO (ml/min/mmHg); deterioration in FVC and DLCO must be confirmed at the subsequent visit within 28 (± 14) days
    • Respiratory hospitalization (hospitalization involving worsening of, or deterioration in respiratory symptoms, gas exchange/hypoxemia, or radiographic findings on chest x-ray or high-resolution computerised tomography (HRCT) scan
    • All-cause mortality


Secondary Outcome Measures:
  • Proportion of Participants With No Disease Progression or Death at 48 Weeks [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    The proportion of participants with no disease progression or death is presented as a percentage using a Kaplan-Meier (KM) estimate of survival or not experiencing disease progression.

  • Change in FVC % Predicted at Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    FVC is defined as the volume of air (liters) that can forcibly be blown out after taking a full breath. FVC % predicted is defined as FVC % of the participant divided by the average FVC % in the population for any person of similar age, sex, and body composition.

  • Change in DLCO % Predicted at Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    DLCO is the extent to which oxygen passes from the air sacs of the lungs into the blood. DLCO % predicted is defined as DLCO % of the participant divided by the average DLCO % in the population for any person of similar age, sex and body composition.

  • Change in 6MWT at Week 48 [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    The 6MWT is a measure of exercise tolerance, and measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface.

  • Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    The range of each health domain score is 0-100, with 0 indicating a poorer health state and 100 indicating a better health state. An increase in score indicates an improvement in health state.

  • Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    The SGRQ is designed to measure impact on overall health, daily life, and perceived well-being in participants with obstructive airways disease. The range of each score is 0-100, with 0 indicating fewer limitations and 100 indicating more limitations; an increase in score indicates an increase in limitations.

  • Change in Dyspnea Score at Week 48 as Assessed by the Transitional Dyspnea Index (TDI) [ Time Frame: Baseline and Week 48 ] [ Designated as safety issue: No ]
    The transitional focal score (-9 to 9) is the sum of relative change from baseline for the Functional Impairment, Magnitude of Task, and Magnitude of Effort scores (each -3 to 3 scale). A TDI score of -9 represents a maximum degradation of all three tests; a score of 9 represents a maximum improvement of all three tests.

  • Percentage of Participants Who Developed PH on Study [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: No ]
    The percentage of participants known to have developed pulmonary hypertension on study documented by right heart catheterization (RHC) was analyzed. RHC was done at baseline and 48 weeks, or at the early termination visit.


Enrollment: 494
Study Start Date: December 2008
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ambrisentan Drug: Ambrisentan
Ambrisentan (5mg or 10 mg tablet) was administered orally once daily.
Other Name: Letairis®
Placebo Comparator: Placebo Drug: Placebo
Placebo to match ambrisentan was administered orally once daily.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or females from 40 to 80 years of age
  • Diagnosis of IPF
  • Honeycombing (fibrosis in the lung) on high-resolution computerised tomography (HRCT) scan of less than or equal to 5%
  • Willing and able to have 2 right heart catheterizations performed
  • Willing to have monthly lab tests to monitor liver function
  • Able to perform the 6 minute walk test (indicated adequate physical function)
  • Must have meet lung function requirements
  • Normal liver function tests
  • Negative serum pregnancy test
  • Willing to use at least 2 reliable methods of contraception
  • Able to understand and willing to sign informed consent form

Exclusion Criteria:

  • No restrictive lung disease (other than usual interstitial pneumonia or IPF)
  • No obstructive lung disease
  • No recent or active respiratory exacerbations
  • No recent hospitalization for an IPF exacerbation
  • No recent history of alcohol abuse
  • Chronic sildenafil (or same drug class) use for pulmonary hypertension
  • Chronic treatment with certain medications for IPF within 30 days of randomization
  • No other serious medical conditions
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00768300

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Hospital
Birmingham, Alabama, United States, 35294
United States, Arizona
Pulmonary Associates
Phoenix, Arizona, United States, 85006
Scottsdale, Arizona, United States, 85258
United States, California
David Geffen School of Medicine at UCLA(Harbor-UCLA Medical Center)
Los Angeles, California, United States, 90095
University of California, Davis
Sacramento, California, United States, 95817
San Diego, California, United States, 92103-8373
San Francisco, California, United States, 94143
Stanford University
Stanford, California, United States, 94305
United States, Colorado
National Jewish Medical And Research Center
Denver, Colorado, United States, 80206
United States, Delaware
Newark, Delaware, United States, 19713
United States, Florida
Bay Area Chest Physicians
Clearwater, Florida, United States, 33756
University of Miami Miller School of Medicine
Miami, Florida, United States, 33136
Tampa, Florida, United States, 33606
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Iowa
Council Bluffs, Iowa, United States, 51503
United States, Kentucky
Kentuckiana Pulmonary Association
Louisville, Kentucky, United States, 40202
Louisville, Kentucky, United States, 40202
United States, Maryland
Baltimore, Maryland, United States, 21205
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Boston, Massachusetts, United States, 02215
Boston, Massachusetts, United States, 02115
United States, Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Saint Lukes Foundation
Chesterfield, Missouri, United States, 63017
United States, New Hampshire
Dartmouth Medical School
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
New Brunswick, New Jersey, United States, 08903
Piscataway, New Jersey, United States, 08854
Pulmonary & Allergy Associates
Summit, New Jersey, United States, 07091
United States, New York
Pulmonary And Critical Care Services, P.C.
Albany, New York, United States, 12205
Winthrop University Hospital
Mineola, New York, United States, 11501
New Hyde Park, New York, United States, 11040
Columbia University Medical Center
New York, New York, United States, 10032
New York, New York, United States, 10029
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Cincinnati, Ohio, United States, 45267
The Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44795
Columbus, Ohio, United States, 43215
United States, Oregon
The Oregon Clinic, P.C.
Portland, Oregon, United States, 97220
United States, Pennsylvania
University of Pennsylvania Health Systems
Philadelphia, Pennsylvania, United States, 19104
Philadelphia, Pennsylvania, United States, 19140
Pittsburgh, Pennsylvania, United States, 15212
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
The Reading Hospital and Medical Center
Reading, Pennsylvania, United States, 19611
United States, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
Lexington, South Carolina, United States, 29072
Spartanburg, South Carolina, United States, 29303
United States, Tennessee
Nashville, Tennessee, United States, 37232
United States, Texas
Houston, Texas, United States, 77030
McKinney, Texas, United States, 75069
United States, Utah
Provo, Utah, United States, 84604
Salt Lake City, Utah, United States, 84108
United States, Virginia
Charlottesville, Virginia, United States, 22908
Falls Church, Virginia, United States, 22042
Lynchburg, Virginia, United States, 24501
United States, Washington
Everett, Washington, United States, 98201
Seattle, Washington, United States, 98195
Argentina
Mar del Plata, Provincia de Buenos Aires, Argentina, B7602DCK
Buenos Aires, Argentina, C1425DES
Ciudad Autonoma de Buenos Aires, Argentina, C1181ACH
Ciudad Autonoma de Buenos Aires, Argentina, C1280AEB
Mar del Plata, Buenos Aires, Argentina, B7602DCK
San Miguel de Tucuman, Argentina, T4000HXU
Australia, New South Wales
Concord, New South Wales, Australia, 2139
Darlinghurst, New South Wales, Australia, 2010
Australia, Queensland
Chermside, Queensland, Australia, 4032
Australia, South Australia
Woodville, South Australia, Australia, 5011
Australia, Tasmania
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Parkville, Victoria, Australia, 3050
Prahran, Victoria, Australia, 3181
Australia, Western Australia
Perth, Western Australia, Australia, 6000
Austria
Graz, Austria, 8036
Innsbruck, Austria, 6020
Linz, Austria, 4020
Wien, Austria, 1090
Belgium
Anderlecht, Belgium, 1070
Bruxelles, Belgium, 1200
Leuven, Belgium, 3000
Yvoir, Belgium, 5530
Brazil
Belo Horizonte, Brazil, 30430-1
Florianopolis, Brazil, 88040-970
Goiania, Brazil, 74605-050
Porto Alegre, Brazil, 90035-074
Porto Alegre, Brazil, 90610-000
Porto Alegre, Brazil, 91350-200
Rio de Janeiro, Brazil, 21949-900
Santo Andre, Brazil, 09060-650
Sao Paolo, Brazil, 04023-062
Canada, Alberta
Calgary, Alberta, Canada, T1Y6J4
Edmondton, Alberta, Canada, T6G 2C8
Canada, British Columbia
Vancouver, British Columbia, Canada, V5Z 1M9
Vancouver, British Columbia, Canada, V6Z 1YP
Canada, Newfoundland and Labrador
St. Johns, Newfoundland and Labrador, Canada, A1B 3V6
Canada, Quebec
Montreal, Quebec, Canada, H2W1T8
Sainte Foy, Quebec, Canada, G1V 4G5
Canada
Toronto, Canada, M4X1104
Chile
Santiago, Chile, 7500691
Talcahuano, Chile, 4270918
Valparaiso, Chile, 2352499
Colombia
Bogota, Colombia
Floridablanca, Colombia
Czech Republic
Brno, Czech Republic, 625-00
Hradec Kralove, Czech Republic, 500 05
Jihlava, Czech Republic, 586 33
Liberec, Czech Republic, 460 63
Olomouc, Czech Republic, 775-20
Plzen, Czech Republic, 305 99
France
Lille, France, 59037
Marseille, France, 13009
Montpellier, France, 34295
Nice, France, 06002
Paris, France, 75015
Paris, France, 75018
Pessac, France, 33604
Rennes, France, 35033
Tours, France, 37044
Germany
Berlin, Germany, 10117
Berlin, Germany, D-13125
Coswig, Germany, 01640
Donaustauf, Germany, 93093
Essen, Germany, D-45239
Freiburg, Germany, 79106
Greifswald, Germany, D-17475
Heidelberg, Germany, 69126
Lowenstein, Germany, D-74245
Munchen, Germany, 81377
Ireland
Dublin, Ireland, 7
Israel
Ashkelon, Israel, 78306
Beer-Sheva, Israel, 84101
Haifa, Israel, 34362
Haifa, Israel, 31096
Jerusalem, Israel, 91031
Jerusalem, Israel, 91120
Petach Tikva, Israel, 49100
Rehovot, Israel, 76100
Tel Aviv, Israel, 64239
Tel-Hashomer, Israel, 52621
Italy
Catania, Italy, 95123
Forlì, Italy, 47100
Milano, Italy, 20123
Milano, Italy, 20132
Modena, Italy, 41100
Napoli, Italy, 80131
Padova, Italy, 35128
Palermo, Italy, 90127
Roma, Italy, 00133
Siena, Italy, 53100
Torino, Italy, 10043
Mexico
Guadalajara, Jalisco, Mexico, 44670
Monterrey, Nuevo Leon, Mexico, 64718
Huixquilucan Edo. de Mexico, Mexico, 52763
Mexico City, DF, Mexico, 14080
Monterrey, Mexico, 64460
Zapopan, Jalisco, Mexico, 45200
Netherlands
Almelo, Netherlands, 7609 PP
Peru
Callao, Peru, Callao 02
Lima, Peru, L31
Lima, Peru, Lima 27
Lima, Peru, L33
Lima, Peru, Lima 41
Lima, Peru, Lima 01
Poland
Bydgoszcz, Poland, 85-681
Lodz, Poland, 90-153
Spain
Cadiz, Andalucia, Spain, 11009
Hospital Virgen del Rocio
Sevilla, Andalucia, Spain, 41011
Oviedo, Asturias, Spain, 33006
Complejo Asistencial Universitario de León
Leon, Castilla, Spain, 24080
Pontevedra, Galicia, Spain, 36071
Pozuelo de Alarcon, Madrid, Communidad de, Spain, 28223
Badalona, Spain, 08916
Barcelona, Spain, 08036
Madrid, Spain, 28007
Switzerland
Basel, Switzerland, 4031
Bern, Switzerland, 3010
Lausanne, Switzerland, 1011
United Kingdom
Sheffield, South Yorkshire, United Kingdom, S10 2JF
Chertsey, Surrey, United Kingdom, KT16 0PZ
Cambridge, United Kingdom, CB2 2QQ
Chelmsford, United Kingdom, CM1 7ET
Edinburgh, United Kingdom, EH16 4SA
Glasgow, United Kingdom, G4 0SF
Liverpool, United Kingdom, L9 7AL
London, United Kingdom, SW3 6NP
London, United Kingdom, NW1 2PG
Mancesheter, United Kingdom, M23 9LT
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Chair: Ganesh Raghu, MD University of Washington, Div. of Pulmonary and Critical Care Medicine Chair
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00768300     History of Changes
Other Study ID Numbers: GS-US-231-0101
Study First Received: October 7, 2008
Results First Received: July 15, 2013
Last Updated: February 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
idiopathic pulmonary fibrosis
interstitial lung disease
ambrisentan

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial

ClinicalTrials.gov processed this record on September 18, 2014