A Phase 2 Study of Tapentadol Extended-Release (JNS024ER) ) in Japanese Participants With Chronic Pain Due to Diabetic Neuropathic Pain or Postherpetic Neuralgia

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of tapentadol extended-release (ER) tablets in Japanese participants with moderate to severe chronic (lasting a long time) pain due to painful diabetic peripheral neuropathy (pain in the extremities related to diabetes-induced nerve damage) or postherpetic neuralgia (pain lasting after condition has healed).

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), and parallel-group (each group of participant will be treated at the same time) comparison study in Japanese participants with chronic pain due to painful diabetic peripheral neuropathy or postherpetic neuralgia. The duration of study will be 14 weeks. The study consists of 3 parts: Screening (1 Week before study commences on Day 1); Treatment (12 weeks and will include 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 up to12 week]); and Follow-up (1 Week). Tapentadol hydrochloride ER oral tablet or matching placebo will be administered twice daily for 12 weeks. Efficacy of the participants will primarily be evaluated through Numerical Rating Scale (NRS). 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 Diabetic Neuropathic Pain or Postherpetic Neuralgia

Conditions
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Pain, Diabetic Neuropathies, Neuralgia, Postherpetic Neuralgia

Intervention / Treatment
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* Drug: Tapentadol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with chronic pain due to painful diabetic neuropathy or postherpetic neuralgia continuing for at least 12 weeks before consent Participants with adjuvant analgesics (antidepressants, antiepileptics and diabetic peripheral neuropathy drugs) or non-opioid treatment and dissatisfied with current treatment (in sense of efficacy and/or safety) for at least consecutive 14 days during the 12 weeks before consent Participants have not experienced treatment with conventional opioids, except for the following cases: Short term use of opioid analgesics for treatment of post-operative acute pain more than 30 days before consent; and temporal use of codeine phosphate or dihydrocodeine phosphate for purposes other than pain relief (for example, for antitussive) more than 2 days before consent Mean pain intensity score of greater than or equal to 5 on an 11-point Numerical Rating Scale during 48 hours before consent and the Investigator or Sub-investigator considers that the participant should be treated with an opioid analgesic HbA1c within 4 weeks before consent less than or equal to 11percent (in participants with diabetic neuropathic pain) Exclusion Criteria: Participants have been treated or treated with a monoamine oxidase inhibitor within 14 days before consent Current or a history of epilepsy or convulsive disorders or hypersensitivity to opioid analgesics Suggested of intracranial hypertension (for example, traumatic encephalopathy) Participants who have complicated condition with uncontrolled or clinically significant arrhythmia, or neuropsychiatric disorders Participants with moderately to severely impaired hepatic function, or severely impaired renal function

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tapentadol<br>Tapentadol hydrochloride extended-release(ER) will be administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks. | Drug: Tapentadol<br>* Tapentadol hydrochloride extended-release(ER) will be administered as oral tablet at dose ranging from 25 milligram (mg) to 250 mg twice daily for 12 weeks.<br>* Other names: JNS024ER;|
| Placebo Comparator: Placebo<br>Matching Placebo will be administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks. | Drug: Placebo<br>* Matching Placebo will be administered as oral tablet at dose ranging from 25 mg to 250 mg twice daily for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Numerical Rating Scale (NRS) Score at Week 12 | Participants were asked to assess the average pain intensity on an 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number on the scale applicable to their pain. Baseline pain score is defined as the average pain intensity score over the last 3 days prior to the randomization. Change from Baseline in NRS score is the mean NRS score at Week 12 minus mean NRS score at Baseline. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Average Numerical Rating Scale (NRS) Score at Week 1 to 11 | Participants were asked to assess the average pain intensity on an 11-point NRS ranging from 0 (no pain) to 10 (maximum pain imaginable) by selecting a number on the scale applicable to their pain. Baseline pain score is defined as the average pain intensity score over the last 3 days prior to the randomization. Change from Baseline in NRS score is the mean NRS score at corresponding week minus mean NRS score at Baseline. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11 | 
| Percentage of Participants With Treatment Response Based on Numerical Rating Scale (NRS) | Percentage of participants with treatment response in mean NRS score by greater than equal to 30 or 50 percent (%) in the last week from baseline were considered as responders. Participants were asked to assess the average pain intensity on an 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 and Week 12 | 
| Number of Participants With Categorical Scores 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 ineffective. | Week 8 and Week 12 | 
| Change From Baseline in Pain Interference Subscale Score Based on Brief Pain Inventory (Short Form) (BPI-sf) Scale | The 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). Pain interference sub-scale score ranges from 0 (do not interfere) to 10 (completely interferes). Higher scores indicates worsening. 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. Lower score indicates an improvement in pain. | Baseline and Week 12 | 
| Change From Baseline in Pain Subscale Score Based on Brief Pain Inventory (Short Form) (BPI-sf) Scale | The 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). Pain Sub-scale score ranges from 0 (absent [no pain]) to 10 (extreme [pain as bad as you can image]). Higher scores indicates worsening. 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. Lower score indicates an improvement in pain. | Baseline and Week 12 | 
| Change From Baseline in Brief Pain Inventory (Short Form) (BPI-sf) Total Score at Week 12 | The 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. Lower score indicates an improvement in pain. | Baseline and Week 12 | 
| Change From Baseline in Sleep Latency Based on Sleep Questionnaire at Week 12 | Sleep Latency was related to How long after bedtime or lights out did the participant fall asleep last night . Decrease in time indicates an improvement. | Baseline and Week 12 | 
| Change From Baseline in Time Slept Based on Sleep Questionnaire at Week 12 | Time slept was related to How long did the participant sleep last night. The mean change for the time in hours slept during the last night was reported. | Baseline and Week 12 | 
| Number of Participants With Awakenings Based on Sleep Questionnaire | Number of awakenings was related to How many times did the participant wake up during the night. Lesser number signifies better sleep. | Baseline and Week 12 | 
| Number of Participants With Response Based on Overall Quality of Sleep Questionnaire | Participants rated the overall quality of sleep last night as excellent, good, fair and poor. | Baseline and Week 12 | 
| Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Scores at Week 12 | The 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 and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic pain, Diabetic Neuropathic Pain, Neuralgia, Postherpetic, Tapentadol hydrochloride extended-release, JNS024ER, Placebo