A Verification Study of a Long-term Use of JNS013 in Patients With Chronic Pain

The purpose of this study is to assess the effectiveness and safety of JNS013 with long-term administration (52 weeks) to patients with chronic pain poorly controlled by NSAIDs.

Since JNS013 is a combination of tramadol hydrochloride (TRAM) acting as a weak opioid with acetaminophen (APAP) inhibiting central COX-3, it is expected to have an intermediate effect between narcotic analgesics and NSAIDs (non-steroid anti-inflammatory drugs).

This study was planned to confirm the safety of JNS013 with long-term administration patients with chronic pain and the effectiveness of JNS013 in diseases associated with chronic pains due to not only knee osteoarthritis (OA) or low back pain (LBP) but rheumatoid arthritis(RA), neck-shoulder-arm syndrome (NSAS), diabetic neurogenic pain (DN) or postherpetic neuralgia(PHN) etc. This study is designed as an open-label (both physician and patient know the name of the study drug), uncontrolled, multicenter study. The duration of treatment is for up to 52 weeks. Of the duration, the first 4 weeks in treatment period is described as treatment period I. During treatment period I, JNS013 will be administered without allowing changes in the content of concomitant medications/therapies, and the effectiveness in various chronic pains will be confirmed. Subsequently, in treatment period II (after 5th week in treatment period), no concomitant medications/therapies will be restricted, and the safety of JNS013 treatment under the normal clinical status will be confirmed.

In addition, the investigator will assess the safety by handling any untoward medical event (including abnormal changes in laboratory data) that occurred in patients from informed consent through the completion of follow-up period as an adverse event. Besides collection of any untoward medical event, laboratory data, Vital signs and body weight will be measured for safety evaluation Patients will select one or two tablets of JNS013 per administration depending on their severity of pain and tolerability. Treatment will be given to patients 4 times daily at no less than 4-hour intervals (up to i8 tablets per day). The treatment period will be for up to 52 weeks. Total study periods: 54 weeks. Screening period: 1 week. Treatment period I: 4 weeks. Treatment period II: 48 weeks Follow-up period: 1 week. Safety evaluations: Adverse events reporting, laboratory test values, blood pressure/pulse rate, body weight JNS013 will be orally administered 4 times daily at least 4-hour intervals (up to 8 tablets per day). The dose will be selected 1 or 2 tablets of JNS013 per administration according to the severity of pain and tolerability by each patient. The treatment period will be for up to 52 weeks.

Inclusion Criteria:

• Sustention of chronic pain due to OA, LBP, RA, NSAS, DN, PHN or other for at least 3 months
• Patients whose pain cannot be controlled sufficiently with at least 14-day continuous treatment with identical oral NSAIDs at a usual maximum dose during 3 months prior to this study
• Outpatients
• Ambulatory patients without need for any supportive device or assistance during daily life
• Patients 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.

Exclusion Criteria:

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