(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

  Show 185 Study Locations
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 July 28, 2014