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Study: Fewer Side Effects Seen With Bicifadine Than Tramadol in Treating Dental Pain

HACKENSACK, N.J., Sept. 10 /PRNewswire-FirstCall/ -- DOV Pharmaceutical, Inc. today announced positive efficacy and safety results for its Phase III clinical trial investigating its novel, non-narcotic analgesic, bicifadine, in the treatment of moderate to severe post-surgical dental pain. These data indicate that bicifadine is an effective analgesic as compared to placebo, with an efficacy at least equivalent to tramadol. In this study, bicifadine produced fewer side effects than tramadol. Bicifadine is not a narcotic and, unlike tramadol, does not have physical dependence liability.

This Phase III confirmatory trial was a single dose, double blind, placebo-controlled study conducted in 540 male and female patients between the ages of 16 and 42. Three dose levels of bicifadine (200, 400 and 600 mg) and one dose level of tramadol (100 mg) were compared to placebo using as a primary endpoint measure the Summed Pain Relief and Intensity Difference (SPRID(6)) score, a measurement tool that reflects the total analgesia produced over an initial six-hour test period. Secondary measures included SPRID(12), the total analgesia produced over a 12-hour test period, as well as maximal analgesia and hourly measures of pain relief.

Bicifadine, in a dose-dependent fashion, produced significant (p<.0001 overall="" increases="" in="" sprid="" scores="" compared="" to="" placebo="" as="" did="" the="" single="" dose="" level="" of="" tramadol.="" statistically="" significant="" analgesia="" were="" measured="" early="" one="" hour="" after="" administration="" and="" these="" effects="" sustained="" for="" balance="" six-hour="" period.="" mean="" maximal="" analgesic="" mg="" doses="" bicifadine="" indistinguishable="" from="" those="" obtained="" with="" all="" three="" tramadol="" produced="" indicating="" an="" extended="" duration="" action.="">

Both bicifadine and tramadol were safe and relatively well tolerated without producing any serious adverse events. Tramadol (100 mg) and the 400 and 600 mg doses of bicifadine produced significantly more adverse events than placebo with the most frequently reported symptoms being nausea and emesis. However, both the 200 and 400 mg doses of bicifadine produced significantly fewer adverse events, including nausea and emesis, than tramadol.

Dr. Frank Caruso, an internationally recognized pain researcher associated with one of the clinical trial sites conducting this study, stated, "These positive results clearly demonstrate the analgesic effects of bicifadine in a well accepted clinical pain procedure. The fact that bicifadine produced dose-proportional analgesic activity vs placebo, comparable analgesic efficacy to a high dose of tramadol (100 mg) and maximal analgesic effects at dosages of 200, 400 and 600 mg that were indistinguishable from tramadol is very impressive. At the same time, both the 200 and 400 mg dosages of bicifadine produced fewer adverse effects than tramadol, suggesting a superior therapeutic safety ratio on the part of bicifadine. Together with the results from the previous dental pain study, these data indicate that bicifadine may indeed represent a new class of analgesic at least as efficacious as tramadol and codeine, but without the limiting effects produced by these drugs."

"We are very pleased by these data and encouraged by the continued positive clinical results shown by bicifadine. The current Phase III study confirms the analgesic effects of bicifadine observed in our previous pivotal trial. The confirmatory results of two pivotal trials in a well-accepted pain model represents an important milestone in the development of bicifadine," said Dr. Bernard Beer, president of DOV. He added, "We look forward to the continued Phase III development program for bicifadine, including the initiation of additional, pivotal Phase III efficacy trials required by the FDA."

Bicifadine is a chemically distinct molecule with a unique profile of pharmacological activity. It has two primary biochemical actions. It enhances and prolongs the actions of norepinephrine and serotonin by inhibiting the transport proteins that terminate their physiological actions. In addition, it interferes with the ability of glutamate to stimulate calcium entry into neurons. Preclinical and clinical studies indicate that any of these individual actions or a combination may account for the analgesic properties of bicifadine.

Bicifadine is not a narcotic and, in preclinical studies, it has been shown not to act at any opiate receptor. In animal models, bicifadine did not demonstrate abuse, addiction or dependence potential. Bicifadine development prior to this study included seven Phase I clinical trials, and 14 Phase II clinical trials, involving over 1,750 patients. DOV conducts a joint venture partnership with Elan Corporation plc to develop controlled release formulations of bicifadine for the treatment of pain.

Source: DOV Pharmaceutical, Inc.

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