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Memantine Significantly Reduces Peripheral
Neuropathy Pain In Diabetics
RICHMOND, CA -- January 25, 2000 -- Neurobiological Technologies, Inc. announced
preliminary results of the company's placebo-controlled Phase IIB, dose-ranging
human clinical trial of Memantine, an orally-available neuroprotective agent for
the treatment of painful peripheral neuropathy in diabetics. This three-armed
study comparing daily doses of placebo, 20 mg and 40 mg of Memantine,
demonstrated statistically significantly less nocturnal pain intensity with 40
mg of Memantine compared to placebo after eight weeks of dosing. In the group
dosed with 20 mg of Memantine, positive trends were seen, but statistical
significance was not observed.
The trial evaluated nighttime pain intensity as reported by the patients
themselves. Patients rated their pain intensity twice daily in a diary by
marking a visual analogue scale 100 millimeters long. The more intense the
patient's pain, the closer he or she marked to the right end of the scale
(100mm). Diary entries began at the screening visit and continued throughout the
eight-week dosing period.
"By the end of this trial, patients receiving daily dosing of 40 mg
Memantine experienced significantly less severe, chronic nighttime pain than
patients receiving placebo," said Lisa U. Carr, M.D., Ph.D., vice president
of medical affairs at NTI(R). "So far these results confirm and extend our
findings from an earlier Phase IIA study. We are now analyzing further efficacy
assessments in order to fully evaluate the clinical implications of these
findings with regards to Memantine's ability to improve overall symptoms of
neuropathy. We also expect to utilize the 40 mg dose in working with the FDA to
design a Phase III study."
"It has been exciting to help evaluate Memantine for this very important
unmet medical need," said Sherwyn Schwartz, M.D., trial investigator at the
Diabetes & Glandular Disease Clinic in San Antonio, Texas. "Most
diabetics will experience some form of neuropathy and many cannot obtain
adequate pain relief from existing treatments. If a Phase III clinical trial
confirms these results, Memantine will bring new hope to my long-suffering
patients."
The randomized, double-blind, placebo-controlled dose-ranging trial enrolled
421 patients at 21 trial sites nationwide and was jointly managed by Quintiles
CNS Therapeutics. Patients were required to have a minimum mean pain intensity
rating of 30 mm prior to enrollment. Patients were randomized to one of three
treatment groups. Two groups of patients received twice daily oral doses of
Memantine, escalating to either 20 mg or 40 mg; the remaining patients received
placebo. The company expects that further trial results will be presented at the
52nd Annual Meeting of the American Academy of Neurology in San Diego, April 29
- May 6, 2000.
Painful peripheral neuropathy, or chronic pain related to damaged peripheral
nerves, is one of the most common complications of diabetes. According to the
American Diabetes Association, 10.3 million people have been diagnosed with
diabetes in the United States, and 60 to 70 percent of people with diabetes have
some form of diabetic nerve damage. Although not all patients with nerve damage
suffer from pain, the company estimates that there were approximately 1,200,000
cases of diabetic neuropathic pain in the U.S. and Europe in 1998.
Diabetics with painful neuropathy experience chronic pain in the lower legs
and feet, making it difficult to stand or walk. At night, pain often interferes
with sleep. Loss of sleep dramatically reduces quality of life. Some patients
obtain relief from tight control of blood glucose levels. Others use topical
analgesic creams and non-steroidal anti-inflammatory drugs (NSAIDs). If these
prove ineffective, drugs such as antidepressants, anticonvulsants or opioids are
prescribed. In the end, the company estimates that approximately half of these
patients do not obtain adequate pain relief.
The causes of painful diabetic neuropathy are not completely understood. A
number of published studies have shown that peripheral nerve damage disrupts
pain pathways in the nervous system, causing nerves to send abnormal signals
that the brain interprets as pain. In effect, the brain is bombarded with pain
signals until its ability to process them is compromised. This leads to a
chronic hypersensitivity to pain perception and can result in progressive
neurological damage.
Memantine is an orally-available compound that appears to restore the
function of damaged nerve cells and block abnormal excitatory signals by
modulating the N-methyl-d-aspartate (NMDA) receptor on cell membranes. It has
been shown to be effective as a neuroprotective agent for moderate to severe
dementia. The company's collaborator, Merz + Co. GmbH & Co. of Frankfurt,
Germany is conducting Phase III clinical trials of Memantine in Europe and the
U.S. for treatment of this condition. In a Phase III human clinical trial of
Memantine in Europe sponsored by Merz, severely demented subjects treated with
Memantine had statistically significant improvement compared to placebo in
internationally accepted measures of functional independence, including bathing,
dressing and self-care. Merz expects to report data from additional late-stage
trials in this indication in spring 2000.
The NIH is evaluating Memantine in a Phase II trial for AIDS-related dementia.
Allergan, Inc. of Irvine, California is testing Memantine in the clinic as a
treatment for opthalmic nerve damage associated with glaucoma. Merz has marketed
Memantine in Germany since 1989 with the labeling "dementia syndrome."
Per ulteriori informazioni, contattare:
Il Neurologo con voi
Via Copernico 59/a Milano 20125
Tel: 03332699103
Posta elettronica: tadeo@ilneurologo.com
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