Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00879229
First received: April 8, 2009
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

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.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
Pulmonary Hypertension
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, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change From Baseline in Six-minute Walk Distance (6MWD). [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    The change from baseline in 6MWD at Week 16 (end of blinded treatment) was evaluated.


Secondary Outcome Measures:
  • Long-term Survival [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 40
Study Start Date: July 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Ambrisentan
Ambrisentan (5 mg or 10 mg tablet) administered orally once daily.
Other Name: Letairis
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.
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.

  Eligibility

Ages Eligible for Study:   35 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00879229

  Show 85 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Hunter Gillies, M.D. Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00879229     History of Changes
Other Study ID Numbers: GS-US-300-0128
Study First Received: April 8, 2009
Results First Received: August 9, 2013
Last Updated: May 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
Idiopathic Pulmonary Fibrosis
Pulmonary Hypertension
PH
IPF
Ambrisentan
ERA
Endothelin Receptor Antagonist
Cardiovascular

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

ClinicalTrials.gov processed this record on November 25, 2014