Diffusion Pharmaceuticals initiates phase I/II clinical trial in patients with peripheral arterial disease

Diffusion Pharmaceuticals LLC, a clinical-stage drug-development company commercializing new drugs for the treatment of unmet medical needs, announced today that it has begun to enroll patients in a Phase I/II clinical trial of its lead drug candidate trans sodium crocetinate (TSC).

The trial, designated NCT00725881 on the clinicaltrials.gov Website, is investigating TSC as a treatment for peripheral arterial disease (PAD) patients who experience the severe leg pain known as intermittent claudication. According to the PAD Coalition, approximately 8 million Americans suffer from the disease. Results from the trial are expected to be announced in early 2010.

This double-blinded, placebo-controlled trial will randomize up to 48 patients at five research sites in the U.S. Primary clinical endpoints of the study are peak walking time and claudication onset time, as demonstrated by exercise treadmill tests. Both endpoints are well-accepted by the medical community and regulatory authorities as reliable indicators of efficacy in intermittent claudication clinical trials. Safety and pharmacokinetic assessments are also being conducted during the trial.

"In addition to advancing a much-needed treatment for peripheral arterial disease patients, this Phase I/II study will also help demonstrate TSC's potential to treat other diseases related to cellular oxygen deprivation," says David G. Kalergis, JD/MBA, Chief Executive Officer of Diffusion Pharmaceuticals. "Such proof-of-concept in humans is a critical step in the advancement of our novel pharmaceutical and will support our plans to apply it to treatments for a broad range of unmet medical needs affecting millions of patients annually."

TSC is the company's lead candidate in a family of first-in-class compounds, representing a new approach to the treatment of conditions characterized by oxygen deprivation (hypoxia) at the cellular level. Using a novel mechanism of action, TSC enhances the diffusion of oxygen through blood plasma, increasing the rate of oxygen transport and thus treating the symptoms of hypoxia at their source.

In 2007, the Company successfully completed a Phase I safety study of TSC. This randomized, double-blind, placebo-controlled, dose-escalation study in 40 subjects evaluated the tolerability and pharmacokinetics of an intravenous bolus injection of TSC in healthy human subjects. The study demonstrated that TSC is well tolerated, and raised no significant clinical safety issues in humans at doses higher than the doses being used in ongoing clinical trials.

This randomized, double-blinded, placebo-controlled trial will consist of four cohorts of 12 patients each, to be enrolled sequentially over an escalating range of TSC dosages. Subjects in the study will receive injections of either TSC or placebo intravenously once daily for five consecutive days. Safety and tolerability will be evaluated in a safety review of each cohort before any patients are enrolled into the next cohort. Patients will be evaluated during the study for safety parameters and for clinical endpoints using a treadmill test at prescribed time points. Follow-up assessments will occur at 5, 14 and 30 days after the last dose. The objectives of the study are to evaluate the safety and pharmacokinetics of multiple doses of TSC; establish a dose-response relationship and effect of TSC on peak walking time and claudication onset time in intermittent claudication patients; determine the effect of TSC on potential hypoxia biomarkers; and evaluate the impact of TSC on quality-of-life parameters using the assessments measured in the Walking Impairment Questionnaire routinely used in PAD research. More information on this trial, designated NCT00725881, can be found on the clinicaltrials.gov Website.

According to information from the National Institutes of Health, the American Heart Association, and the PAD Coalition, approximately 8 million patients in the U.S. suffer from PAD and an estimated 787,500 of them experience intermittent claudication. Cardiovascular disease related to atherosclerosis is a major contributing factor to morbidity and mortality worldwide. PAD is a manifestation of systemic atherosclerosis in which arterial blockages lead to decreased leg blood flow. During exercise or walking this decreased blood flow and the corresponding decrease in available oxygen frequently lead to pain and walking impairment referred to as intermittent claudication. Development of TSC as a treatment for PAD is premised on enhancing the diffusion of oxygen through blood plasma to alleviate the claudication pain caused by hypoxia in the tissues of the legs.