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DOV Pharmaceutical, Inc. Announces Statistically Significant Analgesic Effects of Bicifadine in Phase III Clinical Trial in Patients Following Bunionectomy Surgery

Posted on: Monday, 12 September 2005, 09:00 CDT

HACKENSACK, N.J., Sept. 12 /PRNewswire-FirstCall/ -- DOV Pharmaceutical, Inc. announced today that bicifadine, its novel non-narcotic and non-NSAID analgesic, provided statistically and clinically significant analgesic effects at 400 mg administered three times daily (t.i.d) relative to a placebo control group. These effects were comparable to the analgesia produced by the active-control tramadol 100 mg t.i.d. in patients with moderate-severe pain following bunionectomy surgery. Bicifadine was well- tolerated with no serious adverse events. This trial is the first of four pivotal Phase III efficacy trials required for submission of a New Drug Application to the Food and Drug Administration (FDA) for an indication in the treatment of acute pain. The current results are consistent with the safety and efficacy findings from two other double-blind, placebo-controlled studies in patients with moderate-severe pain following dental surgery.

EFFICACY AND SAFETY RESULTS

The bunionectomy Phase III trial enrolled 325 patients at five sites in the U.S. The design and analysis of the study compared 200 and 400 mg t.i.d. of bicifadine to placebo with 100 mg t.i.d. of tramadol as an active control. The key efficacy endpoint in the study was the analgesic effect seen during the first eight hours of dosing as measured by the sum of the pain relief and intensity differences (SPRID-8). Other efficacy measures included the total of the pain relief scores (TOTPAR-8), the sum of the pain intensity differences (SPID-8), the time to onset of analgesic effects and the pain levels measured after the first dosing period. The results showed that both bicifadine 400 mg t.i.d. and the active control group were statistically superior (p<0.01) to placebo on the SPRID-8, TOTPAR-8 and SPID-8 analgesia scores. The onset of analgesic effect was about 30 minutes for both bicifadine and tramadol. The 200 mg dose of bicifadine resulted in an analgesic effect intermediate between the 400 mg dose and placebo, but did not differ statistically from either group. In the repeat dose period, a conventional endpoint analysis showed that bicifadine 400 mg t.i.d and tramadol 100 mg t.i.d. were more active than placebo over the course of the five-day observation period.

Both bicifadine dosing regimens and the tramadol active-control were safe and well-tolerated. There were no serious adverse events and there were few dropouts due to adverse events. The percentage of patients with adverse events judged to be "possibly-definitely" treatment-related in the bicifadine 400 mg t.i.d. group was approximately 20% higher than the placebo group and did not differ statistically from that of the tramadol control group. The 200 mg t.i.d. dosing arm had the same overall adverse event incidence as the placebo treatment. Consistent with results from prior studies, the most common adverse event was related to the gastro-intestinal system, namely, nausea and emesis for both active treatment groups. Safety measures related to heart rate, blood pressure, EKGs and clinical laboratory tests showed both dose regimens of bicifadine to be safe and well-tolerated.

COMPARISON TO PREVIOUS EFFICACY AND SAFETY RESULTS

DOV has previously conducted two placebo-controlled, single-dose, double- blind, dose-response and active-controlled clinical trials of bicifadine. These trials were in patients with moderate-severe pain following dental surgery (third molar extraction) and enrolled approximately 540 and 750 patients. The results of these trials also demonstrated the 400 mg dose of bicifadine to be superior to placebo and the 200 mg dose to represent the lower end of the dose-response function for acute post-surgical pain. In all three studies, bicifadine was well-tolerated.

"Bicifadine is well tolerated and represents a new class of analgesic with efficacy in moderate to severe acute pain," said Dr. Warren Stern, senior vice president of drug development at DOV. "Preclinical data suggest that it should not carry the abuse liability of opioid analgesics. The current results are notable in that the pain following bunionectomy surgery is generally regarded to be more severe than that following dental surgery. Additionally, the dental pain studies evaluated the efficacy and safety of single doses of bicifadine, whereas the current study evaluated bicifadine effects on repeated dosing over a five-day period."

THIRD ANNUAL SCIENTIFIC SYMPOSIUM

DOV will hold its Third Annual Scientific Symposium in New York City on Oct. 28, 2005. "DOV is excited by the prospect of discussing the details of this bunionectomy trial at our Annual Scientific Symposium," said Dr. Leslie Hudson, president and CEO. "The Symposium also affords us the opportunity to review results from the ongoing open label clinical trial in chronic lower back pain and our strategy for NDA submission of bicifadine for acute and chronic pain, as well as the status of the other compounds in the DOV pipeline."

ABOUT BICIFADINE

Bicifadine is a chemically novel molecule with a unique profile of pharmacological activity. Its primary pharmacological action is to enhance and prolong the actions of norepinephrine and serotonin by inhibiting the transport proteins that terminate their physiological actions. While the Company believes that bicifadine also possesses additional neurochemical properties that contribute to its analgesic effects, the exact nature of these other properties is under investigation. Preclinical studies and clinical trials indicate that either one or a combination of these individual actions 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 does not demonstrate abuse, addiction or dependence potential.

Bicifadine has demonstrated statistically significant analgesic effects in three placebo-controlled clinical trials in patients with pain following third molar dental and bunionectomy surgery, two models of moderate to severe acute pain.

ABOUT DOV

DOV is a biopharmaceutical company focused on the discovery, acquisition, development and commercialization of novel drug candidates for central nervous system and other disorders, including cardiovascular, that involve alterations in neuronal processing. Our product candidates address some of the largest pharmaceutical markets in the world including insomnia, pain, anxiety and depression. Our partner Neurocrine has filed two NDAs for the use of DOV's compound indiplon for the treatment of insomnia.

CAUTIONARY NOTE

Statements in this press release that are not historical facts constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act, each as amended, including statements regarding our expectations with respect to the progress of and level of expenses for our clinical trial programs. You can also identify forward-looking statements by the following words: may, will, should, expect, intend, plan, anticipate, believe, estimate, predict, potential, continue or the negative of these terms or other comparable terminology. We caution you that forward-looking statements are inherently uncertain and are simply point-in-time estimates based on a combination of facts and factors currently known by us about which we cannot be certain. Actual results or events will surely differ and may differ materially from our forward-looking statements as a result of many factors, some of which we may not be able to predict or may not be within our control. Such factors may also materially adversely affect our ability to achieve our objectives and to successfully develop and commercialize our product candidates, including our ability to:

* demonstrate the safety and efficacy of product candidates at each stage of development; * meet our development schedule for our product candidates, including with respect to clinical trial initiation, enrollment and completion; * develop an acceptable development plan under and otherwise achieve the results contemplated by the recent amendment to the existing license agreement with Merck; * meet applicable regulatory standards and receive required regulatory approvals on our anticipated time schedule or at all; * meet obligations and required milestones under our license and other agreements; * obtain and maintain collaborations as required with pharmaceutical partners; * obtain substantial additional funds; * obtain and maintain all necessary patents or licenses; and * produce drug candidates in commercial quantities at reasonable costs and compete successfully against other products and companies.

Factors that may cause our actual results to differ materially from our forward-looking statements include (i) one or more of our product candidates could be shown to cause harmful side effects, (ii) one or more of our product candidates may not exhibit the expected therapeutic results, (iii) we or the FDA may suspend one or more of our clinical trials, (iv) patient recruitment may be slower than expected or patients may drop out of our clinical trials including any future trial of ocinaplon if the present clinical hold is lifted, (v) regulatory approval for our product candidates may not be received or may be delayed, and (vi) performance of our licensees and collaborative partners on whom our success depends may not fulfill their obligations to us. You should also refer to the risks discussed in our other filings with the Securities and Exchange Commission including those contained in our annual report on Form 10-K filed on March 15, 2005. We qualify all our forward- looking statements by these cautionary statements. There may be other factors that may materially affect our forward-looking statements and our future results. Readers should not, therefore, place undue reliance on our forward- looking statements. We do not undertake any obligation and do not intend to update any forward-looking statement.

DOV Pharmaceutical, Inc.

CONTACT: Barbara Duncan, Chief Financial Officer, or Alan Beckhard,Manager, Investor Relations and Corporate Communications, of DOVPharmaceutical, Inc., +1-201-968-0980

Web site: http://www.dovpharm.com/

Source: PRNewswire-FirstCall

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