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

Gilead Sciences

Status and phase: Terminated; Phase 3

Conditions: Pulmonary Hypertension; Idiopathic Pulmonary Fibrosis

Treatments: Drug: Placebo; Drug: Ambrisentan

Study type: Interventional

Funder types: Industry

Identifiers

NCT00879229

GS-US-300-0128

Details and patient eligibility

About

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.

Enrollment: 40 patients

Sex: All

Ages: 35 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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40 participants in 2 patient groups, including a placebo group

Ambrisentan

Experimental group

Description:

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

Treatment:

Drug: Ambrisentan

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo

Drug: Ambrisentan