Safety and Efficacy of Gabapentin in Diabetic Peripheral Neuropathy

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Gabapentin Extended Release (G-ER) Tablets in the Treatment of Patients With Painful Diabetic Peripheral Neuropathy

The purpose of this study is to determine whether a new Gabapentin tablet, is safe and effective for the treatment of painful diabetic peripheral neuropathy.

Inclusion Criteria:

• Men or women 18 years or older with diagnosis of type 1 or type 2 diabetes who have reported symmetrical painful symptoms in distal extremities for 1-5 years prior to the study and whose symptoms are attributable to sensorimotor diabetic peripheral neuropathy (DPN).
• Patients of childbearing potential must have a negative urine pregnancy test at screening/randomization, and must use medically acceptable methods of birth control.
• Patient has pain score of at least 4 on the 11-point Likert numerical rating scale at screening. Potential patients should not be informed of the pain intensity eligibility criterion prior to screening or randomization.
• Patient has a mean baseline week pain intensity of at least 4 on the 11-point Likert scale at the end of a one-week pre-treatment period and has completed at least 4 days of diary entries during the baseline week.
• Patient is on stable regimen of antidiabetes medication at screening that can be maintained during the study.
• Patient has hemoglobin A1c (HbA1c) ≤11% at screening.
• Patient has FPG ≤310 mg/dL at screening.
• Patient must have a minimum washout of greater than 5 times the half-life of the drug of any of several medications
• Patients currently treated with gabapentin or pregabalin at screening may be eligible for the study, but must have tapering period wherein the dose of gabapentin is reduced gradually over a period of at least 7 days plus a 2-day or 3-day washout of gabapentin or pregabalin, respectively, prior to start of the Baseline Week.
• Patient must have adequate eyesight to complete questions on the DiaryPro and SitePro. If a patient is unable to do so (for reasons other than severe eye disease) but a caregiver is available to complete these tasks following instruction from the patient, the caregiver may be trained to accomplish these tasks

Exclusion Criteria:

• Patients who have previously not responded to treatment for DPN with gabapentin at doses of ≥1200 mg/day or pregabalin at doses ≥300 mg/day.
• Patients who previously experienced dose-limiting adverse effects that prevented titration of gabapentin to an effective dose.
• Patient has hypersensitivity to gabapentin.
• Patient is a nursing mother.
• Patient has used injected anesthetics or steroids within 30 days of baseline.
• Patient has certain conditions that could confound evaluation of painful DPN, in particular, amputations other than toes, non-diabetic neurologic disorders (e.g. phantom limb pain), and skin conditions affecting sensation in painful limbs.
• Patient has skin conditions in the area affected by the neuropathy that could alter sensation.
• Patient is in an immunocompromised state.
• Patient has an estimated creatinine clearance of <60 ml/min calculated using the Cockroft Gault method (Appendix 3).
• Patient has had malignancy within past 2 years other than basal cell carcinoma.
• Patient has had gastric reduction surgery.
• Patient has severe chronic diarrhea, chronic constipation [unless attributed to drugs that will be washed out], uncontrolled irritable bowel syndrome (IBS) or unexplained weight loss.
• Patient has any abnormal chemistry or hematology results that are deemed by the investigator to be clinically significant.
• Patient has a history of substance abuse within the past year.
• Patient has had 1 or more visits to an emergency room or hospital within the previous 30 days due to hypoglycemia.
• Patient has a history of seizure (except for infantile febrile seizure) or is at risk of seizure due to head trauma.
• Patient has a history of pernicious anemia, untreated hypothyroidism, chronic hepatitis B or C, hepatitis within the past 3 months, or HIV infection.
• Patient has any other serious medical condition that, in the opinion of the Investigator would jeopardize the safety of the patient or affect the validity of the study results.
• Continuing use of any concomitant medication excluded by Inclusion Criterion 8.
• Patient has participated in a clinical trial of an investigational drug or device within 30 days of the screening visit