NanoDOX^® 1% Doxycycline Monohydrate Hydrogel

The molecular environment of chronic inflammatory diseases, like diabetic foot ulcers, contains abnormally high levels of pro-inflammatory cytokines (TNF-a  and IL-1β) and abnormally high levels of proteases (matrix metalloproteinase (MMPs) and neutrophil elastase), which are theorized to prevent normal wound healing. Doxycycline is an antibiotic that is an inhibitor of high levels of active proteases, including matrix metalloproteinases. Topical treatment of diabetic ulcers with a molecule that reduces inflammation and proteases activity could promote healing by reducing the destruction of endogenous growth factors, receptors, and extra cellular matrix proteins that are essential for wound healing.  Doxycycline is an inexpensive, FDA approved antibiotic that also inhibits MMPs and TNF-a converting enzyme (TACE) activity. Its therapeutic benefit in animal models and clinical studies of ulcerative diseases is due to its ability to inhibit MMPs, not from its antibiotic effect. A published clinical study by Chin has demonstrated that topically applied doxycycline (not NanoDOX^®) is successful in treating diabetic foot ulcers. If these characteristics also apply to the proposed clinical trials then NanoDOX^® would constitute an important new therapeutic tool for the treatment of partial and full thickness diabetic, chronic cutaneous (dermal) ulcers that have adequate blood supply.
NanoDOX^® 1% Doxycycline Monohydrate Hydrogel is a topical gel that is intended for direct contact with the wound and is applied to the entire surface of the wound bed. A secondary dressing, such as gauze or non-adhering dressing, will be applied to cover the NanoDOX^® 1% Doxycycline Monohydrate Hydrogel and wound tissue allowing the NanoDOX^® 1% Doxycycline Monohydrate Hydrogel to provide a moist, wound healing environment.
The current Phase IIa study is an 20-week, double-blind, one center, two-arm study with a two (2) week Run-In, evaluating the efficacy of a once-daily administration of NanoDOX^® 1% Doxycycline Monohydrate Hydrogel topically applied to diabetic ulcers in concert with professionally administered Standard of Care (SoC) procedures as described by Standard Operating Procedure(s) of the Department of Veterans Administration Hospitals. Patients with infected wounds will receive oral antibiotic and will not be included in the topical portion of the study until the infection is shown by wound fluid analysis to be resolved. Following a two (2) week Run-In of all patients to receive SoC treatment for Diabetic Ulcers, patients would have either the investigational material or the placebo applied as a part of their wound care. Each patient would receive 2cc packets of either the test article or the placebo for a once-daily home treatment accompanied by a dressing change.

Nanotherapeutics has entered into a Cooperative Research and Development Agreement (CRADA) with the North Florida/South Georgia Veterans Health System to conduct the phase IIa clinical trial, "A Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of NanoDOX^® 1.0% Doxycycline Monohydrate Hydrogel in Diabetic Adult Subjects with Lower Extremity Ulcers Compared to Placebo Hydrogel," at the Malcom Randall VA Medical Center in Gainesville, Florida. Recruitment began in February 2009.

A pilot study with NanoDOX^® to treat dehisced surgical wounds is being developed in collaboration with Walter Reed Army Medical Center through a Cooperative Research and Development Agreement (CRADA). The study, "Double-Blinded, Single-Site, Pilot Study of NanoDOX^® versus Placebo Hydrogel for Dehisced Surgical Wounds," is expected to begin this summer, supported by funding included in the Fiscal Year 2009 Department of Defense Appropriations Act.