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Ambrisentan Phase III Trial To Begin
"This is a comprehensive trial design that will evaluate the safety and efficacy of ambrisentan in treating PAH patients," stated J. William Freytag, President and CEO of Myogen. "The rapidity with which ARIES I & II began enrolling patients is encouraging given some of the challenges we face regarding competing trials and the availability of existing medications. We hope that we can maintain this early momentum throughout the remainder of the studies."
ARIES I & II are randomized, double-blind, placebo-controlled trials of ambrisentan in patients with PAH. The trials are identical except for the doses of ambrisentan and the geographic locations of the investigative sites. The study design anticipates enrolling 186 patients (62 patients per dose group) for each trial. ARIES I will evaluate ambrisentan doses of 5.0 mg and 10.0 mg administered orally once-a-day for 12 weeks to patients in the United States and Canada. ARIES II will evaluate ambrisentan doses of 2.5 mg and 5.0 mg administered orally once-a-day for 12 weeks to patients in Europe and South America. The primary efficacy endpoint is exercise capacity, measured as the change from baseline in the six-minute walk test distance compared to placebo. Secondary endpoints include Borg Dyspnea Index, WHO Functional Class and a Quality of Life Assessment.
About Pulmonary Arterial Hypertension
PAH is a highly debilitating disease of the lungs characterized by severe constriction of the blood vessels in the lungs leading to very high pulmonary arterial pressures. These high pressures make it difficult for the heart to pump blood through the lungs to be oxygenated. Patients with PAH suffer from extreme shortness of breath as the heart struggles to pump against these high pressures causing such patients to ultimately die of heart failure. PAH can occur with no known underlying cause, or it can occur secondary to diseases like scleroderma (an autoimmune disease of the connective tissues), cirrhosis of the liver, congenital heart defects and HIV infection. PAH afflicts approximately 40,000 patients, predominantly women, in the United States.
Ambrisentan is a type-A selective endothelin receptor antagonist and potent inhibitor of endothelin-induced vasoconstriction. Endothelin is a small peptide hormone that is believed to play a critical role in the control of blood flow and cell growth. Elevated endothelin blood levels are associated with several cardiovascular disease conditions, including pulmonary arterial hypertension, chronic kidney disease, hypertension, chronic heart failure, stroke and reclosure of coronary arteries after balloon angioplasty or stent implantation. Therefore, many scientists believe that agents that block the detrimental effects of endothelin will provide significant benefits in the treatment of these conditions. Ambrisentan is selective for the ET(A) receptor versus the ET(B) receptor and demonstrates high potency, high bioavailability, a half-life that may be suitable for once-a-day dosing, no observed drug-drug interaction and, in the recent phase II study, a low incidence of potential liver toxicity as assessed by liver function tests.
Source: Myogen, Inc.