A Long-term Efficacy and Safety Study of Tramadol Hydrochloride Plus Acetaminophen (JNS013) in Japanese Participants With Chronic Pain

Phase 3

Completed

• Conditions: Chronic Pain
• Interventions: Drug: Tramadol Hydrochloride (HCL) plus Acetaminophen (JNS013)

• Registration Number: NCT00736957
• Lead Sponsor: Janssen Pharmaceutical K.K.

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of tramadol hydrochloride plus acetaminophen (JNS013) with long term administration in participants with chronic pain.

Detailed Description

This is an open-label (both physician and participant know the name of the study drug), non-randomized, multicenter (when more than one hospital or medical school team work on a medical research study) and long-term efficacy and safety study of JNS013 (combination of tramadol hydrochloride (TRAM) with acetaminophen \[APAP\]) in participants with chronic pain (aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain). This study consists of 4 periods; screening period: 1 week, treatment period I: 4 weeks, treatment period II: 48 weeks and follow-up period: 1 week. During Treatment Period I, restrictions on concomitant treatments will be established and the participants will be treated with one or two tablets of JNS013, four times daily for four weeks. During Treatment Period II, the participants will be treated for 48 weeks using the same dosing method and dose level for JNS013 as was used during Treatment Period I, permitting modifications to the concomitant drugs/therapies as during normal medical care. Throughout both Treatment Period I and Treatment Period II, the decision will be made to permit the participants to select to use either one or two tablets of JNS013 per dose according to the extent of the participant's pain and tolerability. The total duration of treatment period will be of 52 weeks. Efficacy will be assessed using change from baseline in Visual Analogue Scale for pain (VAS24) score at the pre-defined time point until Week 52. Participants safety will be monitored throughout the study.

Study Timeline

• Study Start: 2008-05
• Study First Submitted: 2008-08-14
• Study First Submitted QC: 2008-08-15
• Study First Posted: 2008-08-18
• Primary Completion: 2009-10
• Study Completion: 2009-11
• Results First Submitted: 2013-03-25
• Results First Submitted QC: 2013-06-14
• Results First Posted: 2013-06-20
• Status Verified: 2014-06
• Last Update Submitted: 2014-06-23
• Last Update Posted: 2014-07-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 219

Inclusion Criteria

• Participants whose pain cannot be controlled sufficiently with at least 14-day continuous treatment with identical oral non steroid anti inflammatory drugs (NSAIDs) at a usual maximum dose during 3 months prior to this study
• Ambulatory participants without need for any supportive device or assistance during daily life
• Outpatients
• Participants who do not plan to change the therapeutic policy and content of the medications for underlying disease during screening period to the end of Treatment Period I
• Sustention of chronic pain due to Osteo Arthritis (OA), Low Back Pain (LBP), Rheumatoid Arthritis (RA), Neck Shoulder Arm Syndrome (NSAS), Diabetic Neuropathy (DN), Post herpetic Neuralgia (PHN) or other for at least 3 months

Exclusion Criteria

• Participants with conditions for which opioids are contraindicated
• Participants with conditions for which APAP are contraindicated
• Participants with history of convulsion or the possibility of convulsive seizure
• Participants with concurrent, previous, or possible alcohol dependence, drug dependence, or narcotic addiction
• Pregnant Participants or those who may be pregnant, lactating mothers, and Participants who wish pregnancy during the study period.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Tramadol HCL plus Acetaminophen	Tramadol Hydrochloride (HCL) plus Acetaminophen (JNS013)	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in VAS24 Score at Week 52	Baseline and Week 52	Pain over the last 24 hours was assessed by using VAS score ranges from 0 mm=no pain to 100 mm=worst possible pain. An increase in score from baseline represented disease progression and decrease represented improvement.
Change From Baseline in Visual Analogue Scale (VAS24) Score at Week 4	Baseline and Week 4	Pain over the last 24 hours was assessed by using VAS score ranges from 0 millimeter (mm)=no pain to 100 mm=worst possible pain. An increase in score from baseline represented disease progression and decrease represented improvement.

Secondary Outcome Measures

Name	Time	Method
Pain Relief (PAR) Score at Week 4	Week 4	Pain relief was evaluated based on a 5-stage scale from 4 (complete relief) to 0 (no relief). An increase in score represented improvement and decrease represented disease progression
Pain Relief Combined With Pain Intensity Difference (PRID) at Week 4	Week 4	PRID was sum of the PID and PAR for each participant at each evaluation time point (2 hours after dosing, 4 hours after dosing). Pain Intensity was evaluated on a 4-stage scale ranges from 3=severe pain to 0=no pain and PID ranges from -3 (the worst) to +3 (the most improved). PAR ranges from 0 (no improved) to +4 (the most improved). PRID ranges from -3 (the worst) to +7 (the most improved).
Change From Baseline in Short Form-36 (SF-36) Score	Baseline, Week 4 and 52	SF-36 is a metric for general health and Quality of Life (QOL), consists of 8 sub-scale indices related to health and QOL (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health). Each of the sub-scale scores ranged from 0 to 100, where higher values indicate a better health status or a better mental status.
Number of Participants With Improvement From Baseline in VAS24 Score	Week 4 and 52	Pain over the last 24 hours was assessed by using VAS score ranges from 0 mm=no pain to 100 mm=worst possible pain. An increase in score from baseline represented disease progression and decrease represented improvement.
Pain Intensity Difference (PID) at Week 4	Week 4	PID is defined as the amount of change in the pain intensity at each evaluation time point (at 2 and 4 hours after the study drug dosing) from the baseline for each participant. Pain Intensity was evaluated on a 4-stage scale ranging from 3=severe pain to 0=no pain. PID ranges from -3 (the worst) to +3 (the most improved).