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

Study Overview
=================
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.

Official Title
-----------------
A Study of a Long-term Administration of JNS013 in Patients With Chronic Pain

Conditions
-----------------
Chronic Pain

Intervention / Treatment
-----------------
* Drug: Tramadol Hydrochloride (HCL) plus Acetaminophen (JNS013)


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tramadol HCL plus Acetaminophen<br> | Drug: Tramadol Hydrochloride (HCL) plus Acetaminophen (JNS013)<br>* Tramadol hydrochloride 37.5 milligram (mg) plus acetaminophen 325 mg (JNS013) one or two tablets will be given orally four times daily (maximum dose is 8 tablets per day) for 4 weeks during treatment period 1 (restrictions on concomitant treatments will be established) and for 48 weeks during treatment period 2 (permitting modifications to the concomitant drugs/therapies). The dosing interval will be of at least 4 hours.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Visual Analogue Scale (VAS24) Score at 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. | Baseline and Week 4 | 
| Change From Baseline in VAS24 Score at 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. | Baseline and Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Improvement From Baseline in VAS24 Score | 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. | Week 4 and 52 | 
| Pain Intensity Difference (PID) at 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). | Week 4 | 
| Pain Relief (PAR) Score at 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 | Week 4 | 
| Pain Relief Combined With Pain Intensity Difference (PRID) at 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). | Week 4 | 
| Change From Baseline in Short Form-36 (SF-36) Score | 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. | Baseline, Week 4 and 52 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Pain, Acetaminophen, Tramadol, JNS013