Acute and Chronic Dental Pain

November 3, 2008

Array issued positive results from a phase II trial of ARRY 797 for the treatment of post surgical dental pain. This randomized, double-blind, active- and placebo-controlled, parallel-group study enrolled 253 subjects who had undergone elective dental surgery to remove three or more impacted third molars. Following surgery and the development of moderate to severe pain, subjects were randomized to receive either ARRY-797 (200 mg, 400 mg or 600 mg), placebo, or celecoxib (400 mg). In subjects requiring rescue medication six to eighteen hours following dosing, a second dose of either 200 mg ARRY-797 or placebo was administered. In the primary efficacy measure of total pain relief over six hours post dose, ARRY-797 produced a dose-dependent analgesic response compared to placebo (p<0.001). Both ARRY-797 (400 and 600 mg) and celecoxib demonstrated significant analgesic benefit, robust pain relief, and good duration of analgesia over placebo. In the subgroup of subjects requiring rescue medication, administration of a second 200 mg dose of ARRY-797 resulted in statistically significant pain relief compared to placebo (p<0.008). No serious adverse events were reported in the ARRY-797 treated groups, and the overall incidence of adverse events was similar across all treatment groups. ARRY-797 is currently undergoing several additional trials.

December 10, 2007

Targacept issued negative results from a phase II trial of TC-2696 for the treatment of acute post-operative pain. This US based, randomized, double-blind, single-dose trial enrolled one hundred and eighty one subjects. The subjects received 10, 25 or 50 mg TC-2696, ibuprofen (400 mg) or placebo following third molar extraction surgery. Treatment was well tolerated with an adverse event profile similar between all arms. However, TC-2696 did not meet the primary endpoints, superior pain relief four or six hours after dosing as compared to placebo. Targacept plans to fully evaluate the data in order to determine a future course of action for TC-2696.

May 3, 2004

Metaphore Pharmaceuticals reported positive results from a phase II trial investigating M40403, a free-radical fighting enzyme mimetic for the treatment of pain. Results demonstrated M40403 improved the efficacy of morphine by providing a faster onset, longer duration, greater peak effect and greater overall effect. The randomized, double-blind, controlled, parallel group study enrolled 350 subjects with pain following dental surgery and was conducted at two sites in the U.S. Subjects received one of three single intravenous doses of morphine (0.04, 0.08, 0.12 mg/kg) alone or in combination with M40403 (.25 mg/kg). A phase II trial with M40403 is planned for the second quarter of 2004 for the treatment of bunionectomy pain.

September 15, 2003

DOV Pharmaceuticals reported positive results from a phase III trial investigating bicifadine, a non-narcotic analgesic for the treatment of post-surgical dental pain. Results showed that treatment with bicifadine demonstrated significant increases in SPRID (6) scores compared to placebo. SPRID (6), or Summed Pain Relief and Intensity Difference score, is a measure of the total analgesia produced over an initial six-hour test period. Data also showed that significant increases in analgesia were measured as early as one hour after administration and were sustained for the six-hour period. The single dose, double blind, placebo-controlled study enrolled 540 subjects aged 16 and 42. The trial used three dose levels of bicifadine (200, 400 and 600 mg) and one dose level of tramadol (100 mg) compared to placebo.

September 16, 2002

Intranasal Ketamine demonstrated positive phase I/II results in the treatment of moderate to severe pain following oral surgery. Three self-administered doses (10 mg, 30 mg, or 50 mg) of Intranasal Ketamine were received by 40 subjects, who had undergone the removal of two to four molars. Results indicated that in comparison to placebo, Intranasal Ketamine had a significantly faster onset of pain relief with dose-related efficacy and duration of effect. Dose-dependent onset of pain relief occurred within two to 10 minutes following intranasal administration and total pain relief scores were statistically significant for the 50 mg dose. Similar trends were also observed in the 10 mg and 30 mg doses. Intranasal Ketamine is being developed by Innovative Drug Delivery Systems.

August 12, 2002

Positive efficacy and safety results were found in the analysis of a phase II clinical trial of bicifadine for the treatment of moderate to severe post-surgical dental pain. Three doses of bicifadine (200, 400, and 600 mg), a novel, non-narcotic analgesic, were compared to one dose of codeine (60 mg) and to placebo. Over a six-hour test period, the two higher doses of bicifadine produced increases in pain relief within one hour, with maximal analgesic effects at two to three hours. The effects were sustained through the remainder of the test period. Codeine produced significant pain relief within one hour, but not at later time intervals. Compared to placebo, bicifadine yielded a significant increase in the Summed Pain Relief and Intensity Difference (SPRID) score, while codeine did not. Only the 600 mg bicifadine had significantly greater mean maximal analgesic scores than 60 mg codeine. The 400 and 600 mg doses of bicifadine induced significantly more adverse events than placebo. Bicifadine is being developed by DOV Pharmaceutical.