DOV Pharmaceutical Inc has initiated a pivotal, phase III, US clinical trial of bicifadine, its novel analgesic, in approximately 480 patients with moderate to severe acute pain following bunionectomy surgery.

The clinical trial is a randomized, double-blind, placebo-controlled, outpatient, multi-centre study that assesses the efficacy and safety of three dose levels of bicifadine for a five-day period incorporating tramadol as an active control. The primary efficacy endpoint is the Summed Pain Relief and Intensity Difference (SPRID) score, a widely recognized measurement of analgesia. Secondary endpoints include time-to-use of rescue medication, clinical global evaluations and other measures.

Dr. Warren Stern, DOV's senior vice president of Drug Development, stated, "With the initiation of this trial, our first pivotal phase III study following the end of our phase II meeting with the FDA, we begin an important new chapter in the life of the company. This study is the beginning of our large-scale, phase III bicifadine programme for the management of acute pain and chronic lower back pain. Two prior clinical trials with bicifadine demonstrated that it is an effective analgesic in a dental pain model with efficacy superior to placebo and comparable to, or better than, codeine and tramadol."

"We expect this new phase III clinical trial to build upon the acute pain model efficacy database. We are selecting two additional acute pain models required to support an acute pain NDA application and plan to initiate those clinical trials in the first half of 2005. In addition, we plan to initiate, in the first quarter of 2005, the long-term safety clinical trials necessary to support both the acute pain and the chronic lower back pain NDA applications," he added.

In March 2004, DOV and the FDA reached agreement on a plan for the balance of the phase III bicifadine programme necessary to submit an NDA for both acute pain and chronic lower back pain. This clinical trial is expected to serve as one of the four pivotal studies required to support the NDA filing for the management of acute pain.

Bicifadine is a chemically distinct molecule with a unique profile of pharmacological activity. It is not a narcotic and, in preclinical studies, has been shown not to act at any opiate receptor. In animal models, bicifadine does not demonstrate abuse, addiction or dependence potential.