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

• ClinicalTrials.gov Identifier: NCT00768300
• Recruitment Status: Terminated
• First Posted: October 8, 2008
• Results First Posted: April 8, 2014
• Last Update Posted: April 8, 2014
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: October 7, 2008
• First Posted Date: October 8, 2008
• Results First Submitted Date: July 15, 2013
• Results First Posted Date: April 8, 2014
• Last Update Posted Date: April 8, 2014
• Study Start Date: December 2008
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 27, 2014)

Time to Death or Disease (IPF) Progression. [ Time Frame: Up to 48 months ]

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

• Original Primary Outcome Measures (submitted: October 7, 2008): Time to death or disease (IPF) progression. [ Time Frame: Event driven, up to 3 years ]

Current Secondary Outcome Measures (submitted: February 27, 2014)

• Proportion of Participants With No Disease Progression or Death at 48 Weeks [ Time Frame: Baseline and Week 48 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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.

• Original Secondary Outcome Measures (submitted: October 7, 2008): Proportion of subjects with disease progression or death at 48 weeks [ Time Frame: 1 year from enrollment ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: (ARTEMIS-IPF) Randomized, Placebo-Controlled Study to Evaluate Safety and Effectiveness of Ambrisentan in IPF
• 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)
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Idiopathic Pulmonary Fibrosis

Intervention

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

Study Arms

• Experimental: Ambrisentan
  Intervention: Drug: Ambrisentan
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Publications *

• Raghu G, Behr J, Brown KK, Egan JJ, Kawut SM, Flaherty KR, Martinez FJ, Nathan SD, Wells AU, Collard HR, Costabel U, Richeldi L, de Andrade J, Khalil N, Morrison LD, Lederer DJ, Shao L, Li X, Pedersen PS, Montgomery AB, Chien JW, O'Riordan TG; ARTEMIS-IPF Investigators*. Treatment of idiopathic pulmonary fibrosis with ambrisentan: a parallel, randomized trial. Ann Intern Med. 2013 May 7;158(9):641-9. doi: 10.7326/0003-4819-158-9-201305070-00003. Erratum in: Ann Intern Med. 2014 May 6;160(9):658.
• Raghu G, Lynch D, Godwin JD, Webb R, Colby TV, Leslie KO, Behr J, Brown KK, Egan JJ, Flaherty KR, Martinez FJ, Wells AU, Shao L, Zhou H, Pedersen PS, Sood R, Montgomery AB, O'Riordan TG. Diagnosis of idiopathic pulmonary fibrosis with high-resolution CT in patients with little or no radiological evidence of honeycombing: secondary analysis of a randomised, controlled trial. Lancet Respir Med. 2014 Apr;2(4):277-84. doi: 10.1016/S2213-2600(14)70011-6. Epub 2014 Feb 18.
• Chien JW, Richards TJ, Gibson KF, Zhang Y, Lindell KO, Shao L, Lyman SK, Adamkewicz JI, Smith V, Kaminski N, O'Riordan T. Serum lysyl oxidase-like 2 levels and idiopathic pulmonary fibrosis disease progression. Eur Respir J. 2014 May;43(5):1430-8. doi: 10.1183/09031936.00141013. Epub 2013 Oct 31.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 27, 2014): 494
• Original Estimated Enrollment (submitted: October 7, 2008): 600
• Actual Study Completion Date: February 2011
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Colombia, Czech Republic, France, Germany, Ireland, Israel, Italy, Mexico, Netherlands, Peru, Poland, Spain, Switzerland, United Kingdom, United States

Administrative Information

• NCT Number: NCT00768300
• Other Study ID Numbers: GS-US-231-0101
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Chair: Ganesh Raghu, MD; University of Washington, Div. of Pulmonary and Critical Care Medicine Chair

• PRS Account: Gilead Sciences
• Verification Date: February 2014