Oculus Innovative Sciences, Inc. posted additional positive results from its US phase II clinical trial evaluating Microcyn Technology as a topical antimicrobial treatment for mildly infected diabetic foot ulcers.
In the clinically evaluable population of the study (those that complied with the protocol requirements for the duration of the study), the clinical success rate at visit 3 (End of Therapy) for Microcyn-alone-treated patients was 77.8 per cent compared to 61.1 per cent for the levofloxacin plus saline treated patients. Interestingly, the clinical success rate at visit 4 (Test of Cure) for Microcyn-alone-treated patients increased to 93.3 per cent compared to 56.3 per cent for the levofloxacin plus saline-treated patients (p= 0.033). This study was not statistically powered but the high clinical success rate (93.3 per cent) and the p-value (0.033) would suggest the difference is meaningfully positive for the Microcyn-treated patients.
Andres A. Gutierrez M.D., Ph.D., director of medical affairs, said, "This is a remarkable result and certainly not one you would expect in a smaller study. We feel this result, along with previously reported clinical success data in our phase II trial, supportive published results in the literature, and even data presented here at DFCon, all suggest that Microcyn Technology has a potential significant role in the treatment of infected diabetic foot ulcers."
No serious drug-related adverse events were reported in any of the three treatment arms. In the Microcyn-Levofloxacin combination arm, two patients experienced stomach discomfort and amnesia, respectively, both "probably related" to levofloxacin. One patient experienced a burning sensation that was "definitely related" to Microcyn, which is consistent with observations in prior Microcyn studies.
Additionally, in the original announced top-line results based upon a preliminary review of the raw data, it appears there were fewer eradications of bacterial strains in the Microcyn monotherapy arm than in the other two arms. The company continues to analyze the microbiological responses and has identified the overlap of confidence intervals of per-patient microbiological response in the three groups. This would suggest there is not a significant difference between the three treatment arms relative to the per-patient microbiological response.
The company plans to request an end-of-phase II meeting with the FDA to discuss phase II results and define the scope and parameters for advancing the clinical program to a New Drug Application.
Hoji Alimi, CEO and founder of Oculus Innovative Sciences, said, "This additional data reaffirms our belief that Microcyn has the potential to be a benefit to patients with infected diabetic foot ulcers. Microcyn demonstrated a positive clinical success rate, meeting the primary endpoint of clinical cure or improvement of infection. We continue to focus on further analysis of the complete trial data to prepare for our end-of-Phase II meeting with the FDA."
The phase II randomised, open-label study enrolled a total of 66 patients with mildly infected diabetic foot ulcers at 15 US sites. Three treatment arms were evaluated: 1) 20 patients (15 evaluable) received topical Microcyn alone 2) 25 patients (18 evaluable) received topical Microcyn in combination with oral levofloxacin; and 3) 21 patients (16 evaluable) received topical saline in combination with oral levofloxacin.
Patient enrolment criteria in all three treatment arms of the study included appropriate blood perfusion and mildly infected ulcers defined by IDSA classification of "mild" and University of Texas wound classification of "1B." Patients were randomised and treated for a total of 10 days. Designed into the trial were three assessment time points: day three, day 10, and day 24. The design provided flexibility for an optimal design of a phase III trial based on a number of potential positive signals at various time points.
The primary phase II endpoint was clinical cure or improvement of infection at the end of therapy (day 10). Clinical cure of infection is defined as the elimination of all five of the Infectious Diseases Society of America (IDSA) visual symptoms that characterize mildly infected diabetic foot ulcers, including: 1) presence of erythema less than two centimeters around the ulcer, 2) detectable increase in temperature of the wound or periwound area, 3) culturable exudate and/or extension of redness is present, 4) localized swelling or indurations, and 5) localised tenderness or pain. Clinical improvement of infection is defined as the elimination of at least two of the five ISDA symptomatic visual indications.
Levofloxacin was chosen for the control group because it is one of the more potent, broad-spectrum oral antibiotics indicated for the treatment of complicated skin and skin structure infections (CSSSIs). IDSA guidelines also recognize Levofloxacin as an appropriate treatment for the treatment of diabetic foot infections. According to the Datamonitor Pharmaceutical Report, Levofloxacin generated $2.4 billion in global sales in 2005.