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

• ClinicalTrials.gov Identifier: NCT00879229
• Recruitment Status: Terminated
• First Posted: April 9, 2009
• Results First Posted: April 22, 2014
• Last Update Posted: May 15, 2014
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: April 8, 2009
• First Posted Date: April 9, 2009
• Results First Submitted Date: August 9, 2013
• Results First Posted Date: April 22, 2014
• Last Update Posted Date: May 15, 2014
• Study Start Date: July 2009
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 18, 2014)

Change From Baseline in Six-minute Walk Distance (6MWD). [ Time Frame: Baseline to Week 16 ]

The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.

• Original Primary Outcome Measures (submitted: April 8, 2009): Change from baseline in six-minute walk distance (6MWD). [ Time Frame: 16 weeks ]

Current Secondary Outcome Measures (submitted: March 18, 2014)

• Long-term Survival [ Time Frame: Week 48 ]
  Long-term survival was assessed as a Kaplan-Meier (KM) estimate of the percent probability of survival, with censoring at Week 48.
• Transition Dyspnea Index (TDI) [ Time Frame: Baseline to Week 16 ]
  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).
• Change From Baseline in WHO Functional Class [ Time Frame: Baseline to Week 16 ]
  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.
• Change From Baseline in Forced Vital Capacity (FVC) Percent Predicted [ Time Frame: Baseline to Week 16 ]
  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.
• Change From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) [ Time Frame: Baseline to Week 16 ]
  Assessment of the the level of the amino acid fragment NT-proBNP is used to establish prognosis in cardiovascular disease.
• Change From Baseline in the Borg Dyspnea Index (BORG) Immediately Following Exercise [ Time Frame: Baseline to Week 16 ]
  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).
• Hemoglobin-corrected Diffusing Capacity for Carbon Monoxide (DLCO) Percent Predicted [ Time Frame: Baseline to Week 16 ]
  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.
• Change in Quality of Life (QOL) Score as Assessed by the Short-Form 36® (SF-36) [ Time Frame: Baseline to Week 16 ]
  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.
• Change in QOL Score as Assessed by the St. George's Respiratory Questionnaire (SRGQ) [ Time Frame: Baseline to Week 16 ]
  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.

Original Secondary Outcome Measures (submitted: April 8, 2009)

• Long-term survival [ Time Frame: 48 weeks ]
• Borg Dyspnea Index [ Time Frame: 16 weeks ]
• WHO Functional Class [ Time Frame: 16 weeks ]
• Pulmonary Function Tests (FVC and DLCO) [ Time Frame: 16 weeks ]
• BDI/TDI [ Time Frame: 16 weeks ]
• Quality of Life assessments [ Time Frame: 16 weeks ]
• NT-proBNP [ Time Frame: 16 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: ARTEMIS-PH - Study of Ambrisentan in Subjects With Pulmonary Hypertension Associated With Idiopathic Pulmonary Fibrosis
• 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
• Brief 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Idiopathic Pulmonary Fibrosis
• Pulmonary Hypertension

Intervention

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

Study Arms

• Experimental: Ambrisentan
  Participants were randomized to receive ambrisentan treatment at an initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 52 weeks
  Intervention: Drug: Ambrisentan
• Placebo Comparator: Placebo
  Participants were randomized to receive placebo to match ambrisentan for 48 weeks, then transition to ambrisentan treatment at the initial dose of 5 mg for 4 weeks, followed by ambrisentan at the target dose of 10 mg for an additional 4 weeks.
  Interventions:

  • Drug: Ambrisentan
  • Drug: Placebo

• Publications *: Ruocco G, Cekorja B, Rottoli P, Refini RM, Pellegrini M, Di Tommaso C, Del Castillo G, Franci B, Nuti R, Palazzuoli A. Role of BNP and echo measurement for pulmonary hypertension recognition in patients with interstitial lung disease: An algorithm application model. Respir Med. 2015 Mar;109(3):406-15. doi: 10.1016/j.rmed.2014.12.011. Epub 2015 Jan 3.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: January 11, 2011): 40
• Original Estimated Enrollment (submitted: April 8, 2009): 220
• Actual Study Completion Date: February 2011
• Actual Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 35 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: Australia, Austria, Canada, Germany, Italy, United Kingdom, United States
• Removed Location Countries: Belgium, Ireland, Israel

Administrative Information

• NCT Number: NCT00879229
• Other Study ID Numbers: GS-US-300-0128
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Sarah Gilroy, Senior Clinical Program Manager, Gilead Sciences
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Hunter Gillies, M.D.; Gilead Sciences

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