Safety and Efficacy Study for the Treatment of Painful Diabetic Neuropathy

Peripheral neuropathy is a serious complication of diabetes. This form of neuropathy carries a high risk of pain, trophic changes and autonomic dysfunction. There is currently no effective treatment for diabetic neuropathy, and good glycemic control is the only way to minimize the risk of occurrence. Clearly, it would be desirable to prevent, impede, or reverse the disrupting and often life-threatening manifestations of peripheral neuropathy by stimulating growth or regeneration of peripheral nerve axons.

Inclusion criteria

• Age ≥ 18 years to ≤ 75 years
• Documented history of Type I or II diabetes with current treatment control (glycosylated hemoglobin A1c of ≤ 10.0% at Screening) and currently on oral medication and/or insulin
• Diagnosis of painful diabetic peripheral neuropathy in both lower extremities
• Lower extremity pain for at least 6 months
• Visual analog scale (VAS) score of ≥ 40 mm at Initial Screening (0 mm = no pain - 100 mm very severe pain)
• Symptoms from the Brief Pain Neuropathy Screening (BPNS) is ≤ 5 point difference between legs at Initial Screening
• The average daily pain intensity score of the Daily Pain and Sleep Interference Diary completed after medication wash-out is ≥ 4 with a standard deviation ≤ 2
• The physical examination component of the Michigan Neuropathy Screening Instrument Score (MNSI) is ≥ 3 at Screening
• Stable treatment of diabetes for at least 3 months with no anticipated changes in medication regimen, and no new symptoms associated with diabetes
• If female of childbearing potential, negative urine pregnancy test at screening and using acceptable method of birth control during the study

Exclusion criteria

• Peripheral neuropathy caused by condition other than diabetes
• Other pain more severe than neuropathic pain
• Progressive or degenerative neurological disorder
• Myopathy
• Inflammatory disorder of the blood vessels (inflammatory angiopathy, such as Buerger's disease)
• Active infection
• Chronic inflammatory disease (e.g., Crohn's disease, rheumatoid arthritis)
• Positive HIV or HTLV at Screening
• Active Hepatitis B or C as determined by Hepatitis B core antibody (HBcAB), antibody to Hepatitis B antigen (IgG and IgM; HbsAb), Hepatitis B surface antigen (HBsAg) and Hepatitis C antibodies (Anti-HCV) at Screening
• Subjects with known immunosuppression or currently receiving immunosuppressive drugs, chemotherapy or radiation therapy
• Stroke or myocardial infarction within last 3 months
• Ophthalmologic conditions pertinent to proliferative retinopathy or conditions that preclude standard ophthalmologic examination
• Specific laboratory values at Screening including: Hemoglobin < 8.0 g/dL, WBC < 3,000 cells per microliter, platelet count <75,000/mm3, Creatinine > 2.0 mg/dL; AST and/or ALT > 3 times the upper limit of normal or any other clinically significant lab abnormality which in the opinion of the investigator should be exclusionary
• Uncontrolled hypertension as defined as sustained systolic blood pressure (SBP) > 200 mmHg or diastolic BP (DBP) > 110 mmHg at Screening
• Patients with a recent history (< 5 years) of or new screening finding of malignant neoplasm except basal cell carcinoma or squamous cell carcinoma of the skin (if excised and no evidence of recurrence); patients with family history of colon cancer in any first degree relative are excluded unless they have undergone a colonoscopy in the last 12 months with negative findings
• Subjects requiring > 81 mg daily of acetylsalicylic acid; If ≥ 81 mg are taken at screening, subjects may be enrolled if willing/able to switch to another medication
• Use of any opioids; subjects may be enrolled if willing and able to discontinue use of these drugs 14 days prior to starting the 7 Day Daily Pain and Sleep Interference Diary and refrain from taking these drugs for the duration of the study
• Subjects requiring regular COX-2 inhibitor drug(s) or non-specific COX-1/COX-2 inhibiting drugs, or high dose steroids (excepting inhaled steroids).Subjects may be enrolled if willing/able to undergo medication wash-out prior to the first dosing and to refrain from taking these drugs for the duration of the study;
• Major psychiatric disorder in within last 6 months
• Body mass index (BMI) > 45 kg/m2 at Screening
• Any lower extremity amputation
• Use of an investigational drug or treatment in past 6 months
• Unable or unwilling to give informed consent