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

Idiopathic Pulmonary Fibrosis Clinical Trial

— ARTEMIS-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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00768300
• Other study ID #: GS-US-231-0101
• Status: Terminated
• Phase: Phase 3
• First received: October 7, 2008
• Last updated: February 27, 2014
• Start date: December 2008
• Est. completion date: February 2011

Study information

• Verified date: February 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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 494
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Interstitial Pneumonias
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

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

Locations

Country	Name	City	State
Spain	Complejo Asistencial Universitario de León	Leon	Castilla
Spain	Hospital Virgen del Rocio	Sevilla	Andalucia
United States	Pulmonary And Critical Care Services, P.C.	Albany	New York
United States	Emory University	Atlanta	Georgia
United States	University of Alabama at Birmingham Hospital	Birmingham	Alabama
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Saint Lukes Foundation	Chesterfield	Missouri
United States	University of Chicago	Chicago	Illinois
United States	Bay Area Chest Physicians	Clearwater	Florida
United States	The Cleveland Clinic Foundation	Cleveland	Ohio
United States	National Jewish Medical And Research Center	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Dartmouth Medical School	Lebanon	New Hampshire
United States	David Geffen School of Medicine at UCLA(Harbor-UCLA Medical Center)	Los Angeles	California
United States	Kentuckiana Pulmonary Association	Louisville	Kentucky
United States	University of Miami Miller School of Medicine	Miami	Florida
United States	Winthrop University Hospital	Mineola	New York
United States	Columbia University Medical Center	New York	New York
United States	University of Pennsylvania Health Systems	Philadelphia	Pennsylvania
United States	Pulmonary Associates	Phoenix	Arizona
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	The Oregon Clinic, P.C.	Portland	Oregon
United States	The Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California, Davis	Sacramento	California
United States	Stanford University	Stanford	California
United States	Pulmonary & Allergy Associates	Summit	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  Chile,  Colombia,  Czech Republic,  France,  Germany,  Ireland,  Israel,  Italy,  Mexico,  Netherlands,  Peru,  Poland,  Spain,  Switzerland,  United Kingdom, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to Death or Disease (IPF) Progression.	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	Up to 48 months	No
Secondary	Proportion of Participants With No Disease Progression or Death at 48 Weeks	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.	Baseline and Week 48	No
Secondary	Change in FVC % Predicted at 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.	Baseline and Week 48	No
Secondary	Change in DLCO % Predicted at 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.	Baseline and Week 48	No
Secondary	Change in 6MWT at 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.	Baseline and Week 48	No
Secondary	Change in Quality of Life (QOL) Score at Week 48 as Assessed by the Short-Form 36® (SF-36)	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.	Baseline and Week 48	No
Secondary	Change in Quality of Life (QOL) Score at Week 48 as Assessed by the St. George's Respiratory Questionnaire (SGRQ)	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.	Baseline and Week 48	No
Secondary	Change in Dyspnea Score at Week 48 as Assessed by the Transitional Dyspnea Index (TDI)	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.	Baseline and Week 48	No
Secondary	Percentage of Participants Who Developed PH on Study	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.	Up to 48 weeks	No