ATHENA-1: An Open-Label, Multicenter Study of Ambrisentan and Phosphodiesterase Type-5 Inhibitor Combination Therapy in Subjects with Pulmonary Arterial Hypertension Who Have Demonstrated a Suboptimal Response to Phosphodiesterase Type-5 Inhibitor

Study Status

Closed to Enrollment

Study Description

This Phase 4, open-label study will evaluate the efficacy and safety of ambrisentan/PDE-5i combination therapy in patients with pulmonary arterial hypertension (PAH) who have demonstrated a suboptimal response to PDE-5i therapy alone. Eligible subjects will receive ambrisentan in addition to PDE-5i at their current dose.

Only a PDE-5i with an FDA-approved indication for PAH will be administered in this study. The PDE-5i dose must have been constant for at least eight consecutive weeks prior to screening for the study. Of the different types of PDE-5is, Sildenafil citrate (Revatio, Viagra) may be administered at doses ranging from 20mg to 100mg tid. Tadalafil may be administered at a maximum tolerated dose of 40mg qd. The PDE-5i dose must remain constant during the study.

Subjects will receive 5mg ambrisentan once daily for four weeks followed by 10mg daily for 44 weeks. After the week-4 visit, a dose reduction of ambrisentan will be permitted if a subject is not tolerating the drug.

Subjects will be monitored with clinical laboratory tests monthly throughout the study. These tests may be performed at a local phlebotomy lab or at the investigator's clinic. In addition, subjects will be assessed for safety and efficacy at the times of screening and enrollment and Weeks 4, 12, 24, 36 and 48. Cardiopulmonary hemodynamics will be assessed at screening and Week 24 only. CAMPHOR Quality of Life will be assessed every 12 weeks. A right-heart catheterization must be performed during the three weeks between screening and enrollment visits (or at the enrollment visit) and again at the Week 24 visit.

Following study completion, subjects will receive treatment for PAH per the discretion of the investigator.

Sponsor

Gilead Sciences

Key Eligibility

Inclusion criteria:

  • Age between 19 and 75 years
  • Minumum weight of 40 kg. (88 lbs.)
  • Current diagnosis of IPAH, FPAH or PAH that is primarily due to connective tissue disease, inherited heart defects, drug or toxin use or HIV
  • WHO functional class III symptoms
  • Currently receiving sildenafil or tadalafil alone for the treatment of PAH for at least the past 12 weeks
  • Patients who meet all of the following hemodynamic criteria, to be determined by a right-heart catheterization:
    • mPAP of at least 25 mmHG
    • PVR of at least 400 dyne*sec/cm5
    • LCWP or LVEDP of not more than 15 mmHg
  • Patients who meet all of the following pulmonary function test criteria:
    • TKTKTK makes no sense
  • Able to walk at least 150 meters during a six-minute walk test
  • If receiving CCBs or HMG-CoA reductase inhibitors (i.e., statins), patient must be on stable therapy for at least four weeks
  • If diagnosed with HIV, must have stable disease status
Exclusion criteria:
  • Patients with a current PH diagnosis other than IPAH, FPAH or PAH
  • Patients with left ventricular ejection fraction (LVEF) ≤ 40% or clinically significant ischemic, valvular or constrictive heart disease
  • Patients who have received chronic prostanoid or ERA therapy within the past 12 weeks
  • Patients who have discontinued ERA treatment for any adverse reaction other than those associated with liver function test abnormalities
  • Patients who have received IV inotropes within the past two weeks
  • Patients with a serum ALT or AST lab value greater than 2.0 times the upper limit of normal

Principal Investigator

Evelyn M. Horn, MD

Contact

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