September is National Vascular Disease Awareness Month
CHARLOTTESVILLE, Va., Sept. 3 /PRNewswire/ -- 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.
About Multi-Center Trial in Peripheral Arterial Disease Patients:
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.
About Peripheral Arterial Disease and Intermittent Claudication:
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.
Additional Clinical Trials with Trans Sodium Crocetinate (TSC):
Also in 2008, Diffusion Pharmaceuticals will initiate a
proof-of-concept Phase I study evaluating the effect of TSC on the oxygen
levels of brain tumors in patients with high-grade glioma. Published
preclinical work indicates that TSC significantly enhances the tumor
killing power of radiation therapy in a rat brain cancer model. The key
element causing increased susceptibility of the tumor cells to radiation
therapy is believed to be TSC's capability to increase the oxygen levels of
the hypoxic portions of cancerous tumors. Intra-tumoral oxygen
concentration levels, as determined by an oxygen-sensing probe implanted
into the tumors of brain cancer patients, will be collected in this trial,
comparing baseline to post-TSC treatment at escalating doses. Biomarkers of
tumor hypoxia will also be studied and patient safety and tolerability data
will be collected and evaluated.
About Trans Sodium Crocetinate (TSC):
TSC is a proprietary small molecule which uses a novel
diffusion-enhancement approach to treating tissue hypoxia. It has been
shown in numerous animal models of hypoxia-related disease states to
increase oxygen levels to hypoxic tissue, providing significant therapeutic
benefit. By enhancing tissue oxygenation, TSC prevents or mitigates the
underlying hypoxia, creating a new paradigm for the potential treatment of
many hypoxia-related conditions.
About Diffusion Pharmaceuticals LLC:
Diffusion Pharmaceuticals LLC is a clinical-stage drug-development
company commercializing a family of first-in-class drug candidates to treat
serious or life-threatening medical conditions. These proprietary small
molecules use a novel method of action to enhance oxygen diffusion to
oxygen-deprived (hypoxic) tissue. Potential clinical applications include
cancer, critical care uses such as trauma, hemorrhage, stroke, and heart
attack, as well as chronic conditions such as peripheral arterial and
vascular disease, cardiovascular disease, and respiratory disorders.
Enhanced diffusion of oxygen into hypoxic tissue has an important
application in oncology by improving the efficacy of radiation therapy in
cancerous tumors. A Phase I study for Diffusion's lead molecule, trans
sodium crocetinate (TSC), in healthy subjects was successfully completed in
2007. The company recently commenced a Phase I/II dose-range-finding,
safety and efficacy study of TSC in peripheral arterial disease patients
suffering from intermittent claudication and is also developing
proof-of-mechanism studies in cancer patients to support further trials
using TSC in patients who are undergoing radiation therapy. Diffusion
Pharmaceuticals, which is privately held, is located in Charlottesville,
Virginia. For more information, visit http://www.diffusionpharma.com.
SOURCE Diffusion Pharmaceuticals LLC
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Related links:
http://www.diffusionpharma.com
CONTACT:
Tracey Linkous, Director of Communications of
Diffusion Pharmaceuticals LLC, +1-434-220-0718,
tlinkous@diffusionpharma.com
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