Eli Lilly and Company announced that patients with diabetic peripheral neuropathy (DPN) using ruboxistaurin, currently being investigated as a treatment for diabetic microvascular complications, showed improvement in symptoms of DPN. The Phase 2 data were presented during the 56th Annual Meeting of the American Academy of Neurology (AAN).
DPN is a condition caused by microvascular (small blood vessel) damage that affects nerves outside the brain and spinal cord - primarily in the hands and feet - and can lead to foot ulcers and amputations. DPN is the leading cause of non-traumatic lower-limb amputations among people with diabetes in the United States. More than 80,000 amputations due to DPN are performed each year. Sensory symptoms of DPN include numbness, prickling, aching pain, burning pain, lancinating pain, and allodynia (a condition in which ordinarily non-painful stimuli evoke pain, such as a bed sheet touching a leg).
There is no prescription therapy in the United States currently approved to target the underlying process of microvascular damage that leads to DPN. Pre-clinical data show that ruboxistaurin is a specific inhibitor of PKC b, an enzyme that has been implicated in the underlying process of microvascular damage that leads to diabetic microvascular complications.
"These early findings are an encouraging development for patients with diabetic peripheral neuropathy," said Vladimir Skljarevski, M.D., neurologist, senior clinical research physician and investigator for Lilly's ruboxistaurin effort. "We are in the midst of several Phase 3 trials and hope to see continued evidence that ruboxistaurin positively impacts nerve function and sensory symptoms of diabetic peripheral neuropathy while being well-tolerated by patients."
DPN is one of three serious diabetic microvascular complications, along with diabetic retinopathy (affects the eyes) and diabetic nephropathy (affects the kidneys). Ruboxistaurin is being investigated as a possible treatment for all three diabetic microvascular complications.
In a year-long, double-masked, placebo-controlled, Phase 2 trial, ruboxistaurin treatment was found to improve signs and symptoms of DPN based on neurological examination, symptom score and quantitative sensory testing. A total of 205 patients with type 1 or type 2 diabetes with DPN were randomized to receive 32 mg or 64 mg of ruboxistaurin or placebo. Patients taking 32 mg ruboxistaurin showed overall improvement in relevant components of neurological examination and composite scores of nerve function. While the 64 mg group also experienced improvement, efficacy was not as significant.
Eighty-three patients who, at baseline, demonstrated clinically significant symptoms of DPN, according to the Neuropathy Total Symptom Score-6 (NTSS-6) test, were assessed for symptom improvement. (The NTSS-6 questionnaire measures the frequency and intensity of six positive sensory symptoms - numbness, prickling, aching pain, burning pain, lancinating pain and allodynia.) Both groups of patients who received ruboxistaurin demonstrated improvement (p=.065 for 32 mg; p=.015 for 64 mg).
Findings also showed that following one year of treatment, side effects were equally distributed among experimental and placebo groups and that ruboxistaurin was generally well tolerated by the patients. While no cause and effect relationship was established between ruboxistaurin and any event, the most common side effects seen in the trials were diarrhea, headache, nasopharyngitis and cough.