A Study Comparing the Effectiveness and Safety of Tramadol HCl/Acetaminophen Versus Placebo for the Treatment of Painful Neuropathy in Diabetic Patients

A Study Comparing the Effectiveness and Safety of Tramadol HCl/Acetaminophen Versus Placebo for the Treatment of Painful Neuropathy in Diabetic Patients

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Tramadol HCl/Acetaminophen for the Treatment of Painful Diabetic Neuropathy

The purpose of this study is to explore the pain-reieiving effects and safety of tramadol HCl/acetaminophen as compared to placebo in patients experiencing painful diabetic neuropathy. Treatment of neuropathic pain often requires the use of more than one medication. The pain-relieving potential of tramadol HCl/acetaminophen for the treatment of painful diabetic neuropathy comes from the multiple mechanisms of action in this combination pain medication. Patients who experience painful diabetic neuropathy will be enrolled in this study.

Previous studies have shown that tramadol HCl is effective in painful diabetic neuropathy. The treatment of neuropathic pain often requires the use of more than one medication, working through different mechanisms of action, to provide the best pain relief. The pain-relieving potential of tramadol HCl /acetaminophen for the treatment of painful diabetic neuropathy comes from the multiple mechanisms of action in this combination pain medication. This is a multicenter, randomized, double-blind, placebo-controlled, parallel group study. Patients who experience painful diabetic neuropathy will be enrolled. There will be a period of up to 3 weeks during which patients will stop taking medications not allowed by the study. A 7-day baseline period will follow, during which time patients will call into an Interactive Voice Response (IVR) system every night at bedtime to record daily assessments including average daily pain and sleep interference. Patients who enter the double-blind portion of the study will be randomized (like with the toss of a coin) to receive either tramadol HCl/acetaminophen or placebo. The dose of tramadol HCl/acetaminophen or placebo will be gradually increased until the doctor determines the patient is taking an adequate dose; up to 1 or 2 tablets 4 times per day, but not more than 8 tablets per day. Every night at bedtime during the double-blind phase, patients will call the IVR system to report assessments of average daily pain, sleep interference and the number of tablets of study medication taken that day. At the end of the study, patients will be tapered off their study medication. The objective of this study is to compare the analgesic effectiveness and safety of tramadol HCl/acetaminophen versus placebo for the treatment of painful diabetic neuropathy. 1 or 2 tramadol HCl (37.5 milligrams)/acetaminophen (325 milligrams) combination tablets or matching placebo by mouth up to 4 times a day for 66 days

Change in the average of daily pain score recorded in the IVR system from baseline to the patient's final week of treatment with study medication.

Efficacy measured by Brief Pain Inventory, Visual Analogue Scale, Short-Form McGill Pain Questionnaire, Profile of Mood States, SF-36 Health Survey, Physician and Subject Global Impression of Change, average daily sleep interference

Inclusion Criteria: Diagnosis of diabetic neuropathy in both lower extremities Lower extremity pain for at least 3 months Stable treatment of diabetes with drugs or diet for at least 3 months Documented history of Type I or II diabetes with current treatment control (glycosylated hemoglobin A1c of <10%) Documented daily pain on at least 4 of 7 days during baseline period (pain rated at least 5 on scale of 11) In generally good health If female of childbearing potential, using acceptable method of birth control Exclusion Criteria: No failed trials of tramadol HCl or tramadol HCl/acetaminophen No participation in more than 2 clinical trials for treatment of neuropathic pain No more than 2 failed trials of medications for neuropathic pain No use of prohibited concomitant medications No peripheral neuropathy caused by condition other than diabetes No other pain more severe than neuropathic pain No progressive or degenerative neurological disorder No painful peripheral diabetic neuropathy for > 10 years No kidney or liver dysfunction Not pregnant or breast-feeding No unstable medical disease No clinically significant medical conditions No condition that might affect the way the body absorbs or processes the study drug No history of suicide attempt/tendencies No major psychiatric disorder in past 6 months No history of drug or alcohol abuse/dependance in the past 2 years No amputations No active infection of the lower extremity No active foot ulcer No use of an investigational drug in past 30 days

Freeman R, Raskin P, Hewitt DJ, Vorsanger GJ, Jordan DM, Xiang J, Rosenthal NR; CAPSS-237 Study Group. Randomized study of tramadol/acetaminophen versus placebo in painful diabetic peripheral neuropathy. Curr Med Res Opin. 2007 Jan;23(1):147-61. doi: 10.1185/030079906X162674.

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Clinical Study Report: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Tramadol HCl/Acetaminophen for the Treatment of Painful Diabetic Neuropathy