An Efficacy and Safety Study for Tapentadol Extended Release (JNS024ER) in Chronic Pain Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety and to explore the pharmacokinetics (how drugs are absorbed in the body, how they are distributed within the body and how they are removed from the body over time) of tapentadol hydrochloride extended release (ER) tablets in Japanese participants with moderate to severe chronic pain due to osteoarthritis (disorder in which the joints become painful and stiff) of knee or low back pain.

Detailed Description
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This is a randomized (study drug assigned by chance), multi-center (when more than one hospital or medical school team works on a medical research study), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-control (participants are randomly assigned to a test treatment or to an identical-appearing treatment that does not contain the test drug), parallel-group (each group of participants will be treated at the same time) comparison study in participants with chronic pain due to osteoarthritis of knee or low back pain. The study duration will be of 14 weeks, which consists of a screening period of 1 week during which the participants will be evaluated for study eligibility, a treatment period of 12 weeks and a follow-up period of 1 week. The treatment period will consist of titration period (from the initiation of the study treatment to determination of the individual's maintenance dose) and maintenance period (from completion of the titration period to the completion of the treatment period). An optimal dose (maintenance dose) will be determined for each participant during the titration period and the treatment will be continued at the maintenance dose to assess the efficacy and safety. Tapentadol hydrochloride ER tablets 25 to 250 milligram or placebo will be administered orally twice daily. Efficacy and safety of the participants will primarily be evaluated by change from baseline in average pain intensity score based on 11-point Numerical Rating Scale (NRS) and Clinical Opiate Withdrawal Scale (COWS), respectively. Participants' safety will be monitored throughout the study.

Official Title
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Phase II Study of JNS024ER in Japanese Subjects With Chronic Pain Due to Osteoarthritis of the Knee or Low Back Pain

Conditions
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Pain, Low Back Pain, Back Pain, Osteoarthritis, Knee

Intervention / Treatment
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* Drug: Tapentadol Hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with chronic pain due to osteoarthritis of knee or low back pain continuing for at least 12 weeks before informed consent Participants who did not achieve adequate analgesia (pain control) with routine treatment with an oral non-opioid analgesic (drug used to control pain) at its usual upper-limit dose or at an adequate fixed dose for at least 14 consecutive days during the 12 weeks before informed consent Participants who have not experienced treatment with conventional opioids, except for short term use of opioid analgesics for treatment of post-operative acute pain more than 30 days before consent or temporary use of codeine phosphate or dihydrocodeine phosphate for purposes other than pain relief (e.g. for antitussive) more than 2 days before informed consent Participants with average pain intensity score of greater than or equal to 5 on an 11-point Numerical Rating Scale (NRS) during 48 hours before informed consent and are considered requiring opioid treatment by the Investigator Participants who are able to visit the medical institutions throughout the study period Exclusion Criteria: Participants who are taking a monoamine oxidase inhibitor within 14 days before informed consent Participants with current or a history of epilepsy or seizure disorders Participants suspected with intracranial hypertension (e.g. traumatic encephalopathy) Participants with uncontrolled or clinically significant arrhythmia (irregular heart rate) Participants with moderate to severe liver dysfunction or severe renal dysfunction

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tapentadol Hydrochloride<br> | Drug: Tapentadol Hydrochloride<br>* Tapentadol hydrochloride extended release (ER) tablets 25 to 250 milligram (mg) will be administered orally twice daily for 12 weeks. Dose will be adjusted as per Investigator's discretion.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo matched to tapentadol hydrochloride ER tablets 25 to 250 mg will be administered orally twice daily for 12 weeks. Dose will be adjusted as per Investigator's discretion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 11-point Numerical Rating Scale (NRS) at Week 12 | Participants were asked to assess the average pain intensity on a 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number applicable to their pain on the scale. The mean pain intensity during the past 74 hours (3 days) was evaluated at Baseline and the mean pain intensity during the past 12 hours was evaluated at subsequent study visits. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 11-point Numerical Rating Scale (NRS) | Participants were asked to assess the average pain intensity on a 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number applicable to their pain on the scale. The mean pain intensity during the past 74 hours (3 days) was evaluated at Baseline and the mean pain intensity during the past 12 hours was evaluated at subsequent study visits. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 | 
| Percentage of Participants With Response Based on 11-point Numerical Rating Scale (NRS) | Percentage of participants with improvement in mean NRS score by greater than or equal to 30 percent or 50 percent in the last week from Baseline were considered as responders. Participants were asked to assess the average pain intensity on a 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number applicable to their pain on the scale. | Week 12 | 
| Number of Participants With Categorical Scores on Patient's Global Impression of Change (PGIC) Scale | The PGIC is a 7-point scale that requires the participants to assess how much their illness has improved or worsened relative to a Baseline state at the beginning of the intervention. The response options are 1 = very much improved, 2 = much improved, 3 = minimally improve, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. | Week 8, Week 12 | 
| Number of Participants With Response Based on Physician's Global Assessment Scale | Physician's Global Assessment Scale assesses the therapeutic efficacy (effectiveness) of the study drug for pain control on a 2-point scale of effective and not effective. | Week 8, Week 12 | 
| Number of Participants With Presence of Pain Based on Brief Pain Inventory-Short Form (BPI-sf) Scale | BPI-sf is a self-evaluated pain assessment form consisting of 15 items (item 1 - presence of pain, item 2 - pain location, items 3 to 6 - pain severity, item 7 - status of pain treatment, item 8 - efficacy of pain treatment, and items 9a to 9g - interference of pain with daily life). Item 1 for presence of pain assesses the question: Do you have any pain today other than everyday kinds of pain? on a 2-point scale of yes or no. | Baseline, Week 12 | 
| Number of Participants With 50 Percent Pain Relief Based on Brief Pain Inventory-Short Form (BPI-sf) Scale | BPI-sf is a self-evaluated pain assessment form consisting of 15 items (item 1 - presence of pain, item 2 - pain location, items 3 to 6 - pain severity, item 7 - status of pain treatment, item 8 - efficacy of pain treatment, and items 9a to 9g - interference of pain with daily life). Item 8 for efficacy of pain treatment assesses number of participants with at least 50 percent pain relief during the last 24 hours on a scale ranging from 0 percent (no relief) to 100 percent (complete relief). | Baseline, Week 12 | 
| Change From Baseline in Brief Pain Inventory-Short Form (BPI-sf) Total Score at Week 12 | BPI-sf consists of 15 items (item 1 - presence of pain, item 2 - pain location, items 3 to 6 - pain severity, item 7 - status of pain treatment, item 8 - efficacy of pain treatment, and items 9a to 9g - interference of pain with daily life). Total score is defined as the mean scores from items 3, 4, 5, 6 and 9 recorded on an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. Negative change indicates an improvement in pain. | Baseline, Week 12 | 
| Change From Baseline in Sleep Latency Based on Sleep Questionnaire at Week 12 | Sleep Latency was addressed by the question: How long after bedtime/lights out did you fall asleep last night? and the change from Baseline in sleep latency was reported. Decrease in time indicated improvement. | Baseline, Week 12 | 
| Change From Baseline in Time Slept Based on Sleep Questionnaire at Week 12 | Time slept was addressed by the question: How long did you sleep last night? and the change from Baseline in time slept was reported. | Baseline, Week 12 | 
| Number of Participants With Awakenings Based on Sleep Questionnaire | Number of awakenings was addressed by the question: How many times did you wake up during the night?'' and lesser number signified better sleep. | Baseline, Week 12 | 
| Number of Participants With Response Based on Overall Quality of Sleep Questionnaire | Overall quality of sleep was addressed by the question: Please rate the overall quality of your sleep last night and participants could choose one of the following options: excellent, good, fair or poor. | Baseline, Week 12 | 
| Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Scores at Week 12 | SF-36v2 is 36-item form related to 8 health concepts (physical functioning, role physical, role emotional, general health, social functioning, bodily pain, vitality, mental health) and 2 summary scores (physical and mental component summary). Physical functioning, role physical and bodily pain contribute to physical component; role emotional, social functioning and mental health contribute to mental component; and social functioning, vitality, and general health contribute to both. All scores are based on a scale from 0 to 100, with higher scores defining more favorable health state. | Baseline, Week 12 | 
| Change From Baseline in Western Ontario MacMaster Questionnaire (WOMAC) Global Score at Week 12 | WOMAC is a self administered 24-item questionnaire used to evaluate participants with osteoarthritis of the knee. It consists of 3 subscales: pain (5 items), joint stiffness (2 items), and physical function (17 items). Each item is assessed on a 5-point scale from 0 to 4. The global score assesses pain, disability and joint stiffness and ranges from 0 to 96. Higher scores indicate that a symptom is bothersome and physically disabling. | Baseline, Week 12 | 
| Change From Baseline in Roland Morris Disability Questionnaire (RDQ) Score at Week 12 | RDQ scale is used to assess the impact of low back pain on daily activities by participants. The scale consists of 24 item questionnaire with options as Yes/No where Yes is counted as 1 point. The total score ranged from 0 to 24, with higher scores indicating greater disability. | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Low Back Pain, Back Pain, Osteoarthritis, Knee, Tapentadol, Tapentadol Hydrochloride Extended Release