XTL Biopharmaceuticals Ltd. announced the initiation of a phase IIb clinical trial of Bicifadine - a serotonin and norepinephrine reuptake inhibitor (SNRI) - for the treatment of diabetic neuropathic pain.
Bicifadine is being developed for the treatment of diabetic neuropathic pain which represents a significant unmet medical need in the rapidly growing multi-billion dollar neuropathic pain market. Bicifadine is a member of the SNRI drug class, a proven class in the treatment of diabetic neuropathic pain. Bicifadine's efficacy in reducing pain has been clearly demonstrated in over 15 clinical trials in acute pain, and its favourable safety profile has been established in over 3,000 patients. Importantly, Bicifadine has a unique ratio of reuptake inhibition of serotonin versus norepinephrine, which differentiates it from other members of the SNRI drug class.
The phase IIb trial that was launched today is aimed at demonstrating the efficacy of Bicifadine in diabetic neuropathic pain, using a study design that is similar to the successful registration trials of Cymbalta, a member of the SNRI class that is approved for this indication, and other approved agents for neuropathic pain.
The phase IIb study is a randomized, double-blind, placebo-controlled study comparing 200mg 3x/day (tid) and 400mg 3x/day (tid) of Bicifadine versus placebo, with a 1:1:1 randomization between the three arms, in patients with diabetic neuropathic pain. The phase IIb study is designed to enrol approximately 330 patients. Approximately 45 clinical centres in the United States, Europe and India will participate in the study. Following randomization, all patients will enter a 2-week titration period to allow them to gradually escalate up to their target treatment dose. This will be followed by a 12-week steady-state treatment period at the target treatment dose. The primary endpoint of the study is to compare the efficacy of each of the two active doses of bicifadine (200mg tid and 400mg tid) versus placebo in reduction of pain associated with diabetic neuropathy, at baseline (at the time of randomization) versus week 14 (week 12 of the steady-state phase). Pain will be measured based on a 24-hour pain rating using the 11-point Pain Intensity Numeric Rating Scale (formerly referred to as the LIKERT scale).
The lead investigators in the study are Dr. Andrew Boulton, M.D. and Dr. Sherwyn Schwartz, M.D. Dr. Boulton is Professor of Medicine, Division of Endocrinology, Diabetes and Metabolism, at the University of Miami and the University of Manchester, UK. Professor Boulton has been active in clinical research in diabetic neuropathy over the last 25 years and has published over 250 peer reviewed articles on the subject. He was co-chair of the committee that formulated the American Diabetes Association statement on diabetic neuropathy published in Diabetes Care in 2005. Dr. Schwartz is Chief Executive Officer and Chief Medical Officer of DGD Research, Inc. which is the largest diabetes and endocrinology practice in the United States. Dr. Schwartz has over 20 years of clinical research experience in diabetes and diabetic complications, and has participated in hundreds of clinical trials in the field.
Dr. Christine Sang, Director of Translational Pain Research at the Brigham and Women's Hospital, Harvard Medical School, and Chair of XTL's Scientific Advisory Board, commented, "Based on the evidence for the role of SNRI's in the treatment of neuropathic pain, I believe that Bicifadine has strong potential to be successfully developed as a treatment for diabetic neuropathic pain. I am also encouraged by the drug's activity observed in previous acute pain studies and its safety exposure in over 3,000 patients to date."
Dr. Andrew Boulton, Co-Lead Investigator in the study, commented, "This study design is similar to the design of the successful registration trials of duloxetine (Cymbalta) in diabetic neuropathic pain and those of other approved agents. This study is well powered to demonstrate a clinical benefit that is comparable to the approved agents for this disease. I am happy to be involved in this important programme."
Dr. Sherwyn Schwartz, Co-Lead Investigator in the study, commented, "As the head of the largest diabetes centre in the country, I believe that diabetic neuropathic pain continues to be an area of tremendous unmet medical need, as many patients do not adequately respond to the limited number of therapies that are available. I am intrigued by the possibility of having another SNRI with a unique ratio of reuptake inhibition of serotonin versus norepinephrine to offer to my patients."
Ron Bentsur, XTL's chief Executive Officer, commented, "We are very excited to be initiating this late-stage clinical trial for Bicifadine and are enthusiastic about the strong support for this trial from many of the top clinical investigative sites from around the world."
XTL in-licensed the world-wide rights to Bicifadine from Dov Pharmaceutical, Inc. in January 2007.