Arena Pharmaceuticals, Inc. announced results from a phase I clinical trial of APD811, an orally bioavailable agonist of the prostacyclin receptor which is intended for the treatment of Pulmonary Arterial Hypertension, or PAH.
The randomized, double-blind and placebo-controlled trial evaluated the safety, tolerability and pharmacokinetics of 0.03 mg, 0.05 mg, 0.1 mg and 0.2 mg single doses of APD811. The trial evaluated 32 healthy volunteers in four cohorts of eight participants each — six randomized to APD811 and two to placebo. APD811 was rapidly absorbed and demonstrated dose-proportional pharmacokinetic exposure over the tested dose range. The terminal half-life was approximately 20 hours.
The most frequent treatment-emergent adverse events were headache, vomiting, nausea, jaw pain and flushing. Dose-limiting adverse events of nausea and vomiting occurred at the 0.2 mg dose. As compared to placebo, heart rate trended higher at the 0.05 mg, 0.1 mg and 0.2 mg doses and the corrected QT (QTc) interval trended higher at the 0.1 mg and 0.2 mg doses. Arena believes the QTc observation is not supported by preclinical data and will further evaluate this in future studies. No serious adverse events were reported.
“We are encouraged by the results of this early stage clinical trial that suggest APD811 has the potential for once-daily, oral dosing, and our next step will be to evaluate the safety, tolerability and pharmacokinetics of multiple dosing and the optimal titration schedule in a phase I b trial,” said William R Shanahan, MD, Arena's senior vice president and chief medical officer. “The development of APD811 is the result of Arena's continuing commitment to advance our diverse research and development pipeline.”
PAH is a progressive, life-threatening disorder characterized by increased pressure in the arteries that carry blood from the heart to the lungs. The increased pressure strains the heart, which can lead to limited physical activity and a reduced life expectancy. Over time, the heart weakens, can no longer pump blood efficiently and may eventually fail.
APD811, an orally bioavailable agonist of the prostacyclin receptor, is an investigational drug candidate discovered by Arena and intended for the treatment of PAH. Prostacyclin receptor agonists slow disease progression and improve exercise tolerance in PAH patients and are among the treatments administered as standard of care for advanced PAH. Currently available prostacyclin receptor agonists belong to the prostanoid class of molecules, and these products need to be administered frequently or continuously through intravenous, subcutaneous or inhaled delivery methods. Arena believes that an orally bioavailable, non-prostanoid prostacyclin receptor agonist that provides clinical benefits similar to currently available prostacyclin receptor agonists has the potential to improve the standard of care for PAH.
Arena is a clinical-stage biopharmaceutical company focused on discovering, developing and commercializing oral drugs that target G protein-coupled receptors, an important class of validated drug targets, in four major therapeutic areas: cardiovascular, central nervous system, inflammatory and metabolic diseases.