Arena Pharmaceuticals, Inc. announced that it has initiated dosing in a phase 1 clinical trial evaluating APD791, Arena's orally administered, internally discovered drug candidate intended for the treatment of arterial thrombo-embolic diseases. This phase 1 trial is planned to enrol up to 72 healthy adult volunteers and is primarily intended to evaluate the safety and tolerability of single ascending doses of APD791. In addition, the trial will also evaluate the Pharmacokinetics and Pharmacodynamics of APD791.

"Advancing APD791 into phase 1 expands our emerging clinical pipeline of novel therapeutics and further validates our research and development capabilities," said Jack Lief, Arena's president and CEO. "Like Arena's other proprietary and internally discovered drug candidates being clinically evaluated, lorcaserin for obesity and APD125 for insomnia, APD791 may provide significant advantages over current therapies. We anticipate announcing data from this programme around the end of this year."

This phase 1 trial is a randomized, placebo-controlled, double-blind, single-ascending dose trial in healthy male and female volunteers between the ages of 19 and 45 years old. The trial will include up to eight cohorts of nine volunteers each. In each cohort, three volunteers will be assigned to receive placebo and six volunteers will be assigned to receive APD791 in an ascending dose fashion. In addition to evaluating APD791's safety and tolerability profile, the trial will also evaluate the pharmacokinetics and pharmacodynamics of single oral doses of APD791. Pharmacodynamics will be evaluated by measuring ex vivo inhibition of platelet aggregation.

A second phase 1 trial is planned to start after the first trial is completed. The second trial is primarily intended to evaluate the safety and tolerability of multiple ascending doses of APD791. It will also evaluate the pharmacokinetics and pharmacodynamics of multiple oral doses of APD791.

APD791 is a novel, orally available and selective inverse agonist, or inhibitor, of the 5-HT2A serotonin receptor. Serotonin activation of the 5- HT2A receptor on platelets and vascular smooth muscle is thought to play an important role in the events leading to thrombosis, and elevated serotonin levels have been associated with increased cardiovascular risk. Normally, when a platelet is activated by one of a number of factors, such as thrombin or collagen, the platelet releases serotonin, which in preclinical studies promotes platelet aggregation, vasoconstriction and intimal hyperplasia (or thickening of the vessel wall). By blocking activation of the 5-HT2A receptor on platelets and other cardiovascular tissues, APD791 may curb these serotonin mediated effects in the clinical setting, thereby reducing the risk of thrombosis. APD791 demonstrated improved coronary artery flow in a preclinical study using the Folts model, an established model of acute coronary syndrome.

Thrombosis is the formation of a clot, or thrombus, inside a blood vessel that restricts the flow of blood. The formation of a thrombus is often caused by an injury to the wall of a blood vessel. The injury to the blood vessel activates platelets, which then aggregate and adhere to one another as they start to release certain factors, including serotonin, that facilitate thrombosis. Thrombi that form in diseased atherosclerotic arteries of the heart may cause acute coronary syndrome or myocardial infarction, and thrombi that form in the vessels of the brain may cause stroke.