A Study to Compare Safety and Efficacy of Tramadol Hydrochloride/Acetaminophen With Gabapentin in Participants With Diabetic Neuropathy

Comparison of the Effectiveness and Safety Between Tramadol 37.5 Mg/Acetaminophen 325mg And Gabapentin for The Treatment of Painful Diabetic Neuropathy: Multicenter, Randomized, Open Comparative Study

The purpose of this study is to evaluate the effectiveness and safety of tramadol hydrochloride (HCl) 37.5 miligram (mg)/acetaminophen 325 mg compared to gabapentin in participants with diabetic neuropathic (nerve disorder caused by diabetes mellitus) pain.

Study Overview

• Status: Completed
• Conditions: Diabetic Neuropathy
• Intervention / Treatment: Drug: Tramadol hydrochloride/ Acetaminophen; Drug: Gabapentin

Detailed Description

This is an open-label (a medical research study in which participants and researchers are told which treatments the participants are receiving, "unblinded"), multi-center and randomized (study drug is assigned by chance) study to compare the effectiveness and safety of tramadol HCl 37.5 mg/acetaminophen 325 mg with gabapentin in participants with diabetic neuropathy. The study will consist of 4 periods: Screening period (up to Day -14), Randomization period (Day 1), Dosage adjustment period (Day 15) and Maintenance period (Day 43). The participants will be randomly assigned to 1 of the 2 treatment groups: tramadol HCl 37.5 mg/acetaminophen 325 mg or gabapentin. Tramadol Hcl/acetaminophen group will receive 1 tablet for 3 days, then 1 tablet twice daily for 4 days followed by 1 tablet thrice daily for next 7 days. If there is no pain relief, the dosage can be increased up to 8 tablets per day for Day 15 to 28, and then the increased dosage will be maintained for Day 29 to 42. Gabapentin group will receive 300 mg on Day 1, 300 mg twice daily on Day 2, and 300 mg thrice daily for Day 3 to 7. Then for Day 8 to 14, participants will receive 300 mg in the morning, 300 mg in the midday and 600 mg in the evening. If there is no pain relief, gabapentin can be increased up to 3600 mg per day for Day 15 to 28, and then the increased dosage will be maintained for Day 29 to 42. Primarily, efficacy will be evaluated by pain intensity using numeric rating scale (NRS). Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 162
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants having painful symmetric neuropathy (a disturbance in the function of the brain or spinal cord that may affect the nerves and muscles of the body) in the lower limbs applicable to both of the following conditions: decreased sensation of leg to monofilament, none or decreased ankle reflexes or decreased vibratory sensation and pain symptoms such as numbness (loss of sensation), tingling, paresthesia (a skin sensation, such as burning, prickling, itching, or tingling, with no apparent physical cause), burning, shooting pain, stabbing or lancinating (characterized by a sensation of cutting, piercing, or stabbing) pain
• Participants having painful diabetic neuropathy in the lower limbs for 3 months before randomization
• Participants diagnosed with Type ll diabetes and stable blood sugar level controlled with an oral medication, insulin or diet therapy for 3 months before randomization
• Participants with glycated hemoglobin (HbA1c) less than or equal to 10 percent
• Participants with pain intensity score of greater than or equal to 4 on numeric rating scale (NRS) for the last 48 hours

Exclusion Criteria:

• Participants who have previously experienced failure of tramadol treatment or have discontinued tramadol administration due to adverse event
• Participants who have received the prohibited medication before randomization (e.g., capsaicin, use of systemic steroids, steroid or local anesthetic injections, tramadol HCl or tramadol combination, gabapentin, opioid analgesics, antidepressants, anticonvulsants, alpha-lipoic acid, acupuncture, COX-2 selective inhibitors, long-acting NSAIDs, opioid analgesics, sedative-hypnotics, muscle relaxants, anxiolytics, antipsychotics, TENS, short-acting non-opioid analgesics)
• Participants with neuropathic pain caused by other reasons (e.g., alcohol abuse, connective tissue disease, toxic exposure, infection, neoplasm, ischemia)
• Participants suffering from painful diabetic neuropathy over 10 years
• Participants with physical damage or disease which may cause abnormal absorption, excessive accumulation, metabolism or excretion disorder of the study medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tramadol hydrochloride (HCl)/ Acetaminophen; Participants will receive 1 tablet containing tramadol HCl 37.5 milligram (mg) and acetaminophen 325 mg once daily, at bed time on Days 1 to 3, 1 tablet twice daily on Days 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there is no pain relief, the dosage can be increased up to 8 tablets per day for Days 15 to 28. The increased dose will be maintained for Days 29 to 42.	Drug: Tramadol hydrochloride/ Acetaminophen; Participants will receive 1 tablet containing tramadol HCl 37.5 milligram (mg) and acetaminophen 325 mg once daily, at bed time on Days 1 to 3,. 1 tablet twice daily on Days 4 to 7 and 1 tablet thrice daily on Day 8 to 14. If there is no pain relief, the dosage can be increased up to 8 tablets per day for Days 15 to 28. The increased dose will be maintained for Days 29 to 42.; Other Names: Ultracet
Active Comparator: Gabapentin; Participants will receive Gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg will be administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there is no pain relief, the dosage can be increased up to 3600 mg per day for Days 15 to 28. The increased dose will be maintained for Days 29 to 42.	Drug: Gabapentin; Participants will receive Gabapentin 300 mg once daily at bed time on Day 1, 300 mg twice daily on Day 2 and 300 mg thrice daily on Day 3. Gabapentin 300 mg will be administered twice daily (in the morning and midday) and gabapentin 600 mg in the evening on Day 8 to 14. If there is no pain relief, the dosage can be increased up to 3600 mg per day for Days 15 to 28. The increased dose will be maintained for Days 29 to 42.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Pain Intensity Score at Day 43	Pain intensity was assessed on 11-point numerical rating scale ranging from 0=no pain to 10=pain as bad as you can imagine.	Baseline and Day 43

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Pain Relief	Pain relief was assessed on a scale ranging from -1 to 4, where -1=became worse, 0=no change, 1=relieved a little, 2=relieved moderately, 3=relieved a lot and 4=completely resolved.	Day 15, Day 29 and Day 43
Overall Assessment of Study Medication by Participants	Overall assessment of study medication was done by participants. Assessment was made on a scale of -2 to 2 where, -2=very bad, -1=bad, 0=no change, 1= good and 2=very good.	Day 43
Overall Assessment of Study Medication by Investigator	Overall assessment of study medication was done by Investigator. Assessment was made on a scale of -2 to 2 where, -2=very bad, -1=bad, 0=no change, 1= good and 2=very good.	Day 43
Change From Baseline in Brief Pain Inventory (BPI) Score at Day 43	The BPI is a questionnaire designed to assess the severity and impact of pain on quality of life. Pain severity score is caculated by sum of all severity items (pain worst, pain least, pain average and pain now) divided by pain now. Total score for pain severity ranges from 0=no pain to 10=extreme pain. Pain interference score was calculated by sum of all interference items (general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life) score. Total score for pain interference ranges from 0=no interference to 70= interferes completely.	Baseline and Day 43
Change From Baseline in Short Form-36 (SF-36) Score at Day 43	The SF-36 is designed to assess the health status of participants. The SF-36 includes 1 multi-item scale measuring physical health and mental health. Physical health includes physical functioning, role limitations due to physical health, pain and general health. Mantal health includes role limitations due to emotional problems, energy/fatigue, emotional well being and social functioning. Each item is scored on a 0-100 range so that the lowest and highest possible scores are set at 0 and 100, respectively. All items are scored so that a high score defines a more favorable health state.	Baseline and Day 43

Collaborators and Investigators

• Sponsor: Janssen Korea, Ltd., Korea

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: March 6, 2008
• First Submitted That Met QC Criteria: March 6, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Estimate): August 12, 2013
• Last Update Submitted That Met QC Criteria: July 26, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Gabapentin; Diabetic neuropathy; Acetaminophen; Tramadol hydrochloride; Ultracet
• Additional Relevant MeSH Terms: Nervous System Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Neuromuscular Diseases; Peripheral Nervous System Diseases; Diabetic Neuropathies; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin; Acetaminophen; Tramadol
• Other Study ID Numbers: CR012967; ULT-KOR-06