BioDelivery Sciences International Inc, has completed enrollment of all patients required for its initial Phase 3 study of Clonidine Topical Gel for the treatment of painful diabetic neuropathy (PDN).

The Phase 3 trial is a multicentre, randomised, double-blind, placebo-controlled study to determine the efficacy and safety of Clonidine Topical Gel in the treatment of pain associated with PDN.  In the trial, referred to as the RHAPSODY Study, subjects are randomised to receive either Clonidine Topical Gel or a placebo gel.  One hundred and forty adult subjects have been randomized into the 12 week double-blind treatment phase of the study.  This is the first of two pivotal trials that would be required for submission of a New Drug Application (NDA) to the US Food and Drug Administration (US FDA).  FDA has granted Fast Track designation for the programme, which recognises the need of developing new therapies for this serious condition.

"We are very pleased with the rapid progression of this study, which we expect will allow for an independent interim analysis based on 50 per cent of the patients completed during the third quarter of this year  one quarter ahead of schedule," said Dr. Andrew Finn, executive vice president of product development.  "The expeditious enrollment of this study in part illustrates the significant unmet need that exists for new treatment options for patients suffering from painful diabetic neuropathy.  Based on the enrollment of this trial, and assuming no additional patients will be required following the interim analysis, we should have top-line study results by the end of the year."

BDSI met with representatives of the FDA on November 21, 2013 to discuss the proposed clinical development programme for Clonidine Topical Gel for the treatment of PDN.  The FDA agreed with the overall clinical programme proposed by BDSI, which includes two well controlled studies and one long-term safety study in patients suffering from PDN, the duration of treatment required for the safety assessment, the plan for data integration from prior and planned clinical studies and the interim analysis of the first pivotal trial.  BDSI is now rolling over patients from the first Phase 3 trial into the 12-month long-term safety study and anticipates starting the second pivotal study in the first quarter of next year.  The overall programme is being conducted in subjects demonstrating functional skin nociceptors, which is the population of patients that demonstrated a statistically significant difference compared to placebo on the primary efficacy endpoint in a previously conducted Phase 2 study.

Nearly 26 million people in the US have diabetes according to the American Diabetes Association. A substantial number of these people have peripheral neuropathy as manifest by impaired sensation and pain in the extremities, most often the feet.  Patients with PDN often experience debilitating pain symptoms that affect day-to-day functioning and quality of life.

BDSI is currently studying whether Clonidine Topical Gel can relieve pain caused by PDN by decreasing the abnormal hyper-excitability of skin nociceptors.  Currently available oral treatments are modestly effective in relieving symptoms and are limited by systemic side effects and drug interactions.  There are no topical products approved for the treatment of PDN.

Oral medications that are approved for the treatment of PDN include anticonvulsants such as Lyrica (pregabalin), the antidepressant Cymbalta (duloxetine) and the opioid Nucynta (tapentadol), with sales for the treatment of neuropathic pain totaling over $3 billion in the US according to Datamonitor.  BDSI believes that Clonidine Topical Gel offers a novel mechanism of action to the available therapies with a potentially improved safety and tolerability profile.  BDSI estimates annual peak sales potential for this product in excess of $300 million.  BDSI is the worldwide licensee of development and commercialisation rights to Clonidine Topical Gel for PDN under a licence with Arcion Therapeutics.