Arena Pharmaceuticals has announced results from a phase I clinical trial of APD811, an orally bioavailable agonist of the prostacyclin receptor intended for the treatment of pulmonary arterial hypertension, or PAH.
The randomized, double-blind, placebo-controlled trial evaluated the safety, tolerability and pharmacokinetics of 0.03mg, 0.05mg, 0.1mg and 0.2mg 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 0.2mg dose. As compared to placebo, heart rate trended higher at the 0.05mg, 0.1mg and 0.2mg doses and the corrected QT (QTc) interval trended higher at the 0.1mg and 0.2mg doses. Arena believes the QTc observation is not supported by pre-clinical 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 Ib trial," said William R. Shanahan, M.D., Arena's senior vice president and Chief Medical Officer.