Phase 2 Study of Tapentadol Prolonged Release in Cancer 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 pharmacokinetics (how the drug is absorbed in the body, distributed within the body, and how it is removed from the body over time; explores what the body does to the drug) of tapentadol prolonged release (JNS024PR, PR) in participants with moderate to severe cancer (abnormal tissue that grows and spreads in the body until it kills) pain.

Detailed Description
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This is a Phase 2 open-label (all people know the identity of the intervention), multi-centric (conducted in more than one center), non-comparative, optional dose-titration study of tapentadol PR in Japanese participants with cancer pain. This study will consist of Screening period (3 to 7 days), Dose adjustment period (3 to 14 days), Fixed dose period (5 days) and Follow-up period (7 days). Tapentadol PR will be administered orally (taken by mouth; to be swallowed) twice daily before meal. For participants previously using opioids, the initial dose of tapentadol PR will be selected depending on the daily dose of opioid at the completion of Screening period. For opioid-naive (moderate to severe cancer pain that is not controlled adequately with non-opioid medications) participants, the initial dose of tapentadol PR will be 25 milligram (mg) twice daily. Participants will receive the same dose of tapentadol PR for the first 2 days of the dose adjustment period and from Day 3, the dose can be titrated as per the Investigator's discretion up to Day 14. After that participants will receive fixed dose regimen for 5 days at the same dose as that used at the end of the dose adjustment period. Efficacy will primarily be evaluated by sustained pain control for the 5 day fixed dose phase. Participants' safety will be monitored throughout the study.

Official Title
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Phase II Study of JNS024PR in Cancer Pain Patients

Conditions
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Pain, Cancer

Intervention / Treatment
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* Drug: Tapentadol PR


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Opioid switching participants should meet the following criteria from a to c: a) Participants with cancer pain b) previously were on opioid medications (morphine sustained release preparations [120 milligram per day {mg/day} or less], oxycodone hydrochloride sustained release tablets [80 mg/day or less], fentanyl transdermal [through the skin] application system [4.2 mg or less]) c) had achieved adequate pain control with opioid therapy Opioid naive participants should meet the following criteria from a to b: a) Participants with cancer pain b) should not have received any pain control therapy with opioids (excluding narcotic antagonist analgesics [drug used to control pain]) Definite diagnosis of any type of cancer, which has been notified to the participant Participants who can be hospitalized during the treatment period Participant who can record 11 point Numerical Rating Scale (NRS) and 100 millimeter (mm) Visual Analog Scale (VAS) scores appropriately throughout the study Exclusion Criteria: Participants with bradyarrhythmia (slow, irregular heartbeats) History of mild or moderate traumatic (causing damage, like a toll used to crush tissue) encephalopathy, cerebral (having to do with the cerebrum) infarction (death of tissue because of lack of blood supply) or transient ischemic (decreased oxygen in a tissue [usually because of decreased blood flow]) attack within 1 year before informed consent Previous or concurrent epilepsy (seizure disorder) or convulsive diseases accompanied by disturbance of consciousness Previous or concurrent alcohol dependence or narcotic abuse History of active hepatitis (inflammation of the liver) B or C within 3 months before informed consent

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Opioid-Naive Participants (Tapentadol PR)<br>Opioid-naive participants are defined as those who had moderate to severe cancer pain that is not controlled sufficiently with non-opioid medications. Treatment period comprises of Titration and Maintenance period. Titration period (3-14 days) is duration between start of treatment to day before initial dose in the maintenance period. Treatment will be initiated with tapentadol prolonged release (JNS024PR, PR) 25 milligram (mg) oral tablet twice daily. Dose will be increased or decreased as per Investigator's discretion up to Day 14. Maximum dose limit will be 500 mg per day. Participants will then be assigned to the treatment in the maintenance period (15-19 days). The maintenance period is duration between the first dose and the final assessment in the maintenance period. Participants will receive tapentadol PR oral tablet twice daily for 5 days at the same dose used on last day of titration period. | Drug: Tapentadol PR<br>* Tapentadol PR tablets will be administered orally twice daily initiated at dose of 25 mg. Dose will be adjusted as per Investigator's discretion. Maximum dose limit is 500 mg per day. Total duration of treatment is 19 days.<br>* Other names: Tapentadol hydrochloride, JNS024;|
| Experimental: Opioid-Switch Participants (Tapentadol PR)<br>Opioid-switching participants are defined as those who had moderate to severe cancer pain that is controlled sufficiently with opioid therapy. Treatment period comprises of Titration and Maintenance period. Titration period (3-14 days) is duration between start of treatment to day before initial dose in maintenance period. Initial dose of tapentadol PR is selected according to daily dose of opioid (morphine sustained release [SR] preparation, oxycodone hydrochloride [HCl] SR tablet or fentanyl patch). Equivalent dose of tapentadol PR oral tablet twice daily is given depending on daily dose of opioid at completion of Screening period. Maximum dose limit is 500 mg per day. Participants will then be assigned to treatment in maintenance period (15-19 days). Maintenance period is defined as duration between first dose and final assessment in maintenance period. Participants will receive tapentadol PR oral tablet twice daily for 5 days at same dose used on last day of titration period. | Drug: Tapentadol PR<br>* Tapentadol PR tablets will be administered orally twice daily initiated at dose of 25 mg. Dose will be adjusted as per Investigator's discretion. Maximum dose limit is 500 mg per day. Total duration of treatment is 19 days.<br>* Other names: Tapentadol hydrochloride, JNS024;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Pain Control for 5 Day Fixed Dose Phase | Percentage of participants with sustained pain control for 5 day fixed dose phase were the participants who completed 5 day maintenance period, whose mean Numerical Rating Scale (NRS) score during the fixed dose phase and which was assessed immediately before giving each dose was less than 4 and the number of rescue doses per day for fixed dose phase was 2 or less. Pain intensity scores were recorded 0 to 30 minutes before dose on 11 point NRS where 0 = no pain and 10 = severest pain imaginable. | Day 15 up to Day 19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Achieve Dose Adjustment | Percentage of participants who achieved dose adjustment included those participants whose dose was adjusted during the titration period period and entered the fixed dose maintenance period. Titration period (3-14 days) was the duration between start of treatment to the day before the initial dose in the maintenance period. Maintenance period (15-19 days) was the duration between the first dose and the final assessment in the maintenance period. | Day 3 up to Day 14 | 
| Pain Assessment Using 24-hour Numerical Rating Scores (NRS) Scale | Pain intensity scores were measured on 11 point NRS, where 0 = no pain and 10 = severest pain imaginable. The pain intensity at Baseline was the average of scores on two consecutive morning doses (Day -1 and Day 0) and on Day 20 only a single observation was recorded. | Baseline (Average of Day -1 and Day 0 morning scores), Day 20 | 
| Pain Assessment Using Visual Analog Scale (VAS) Score | Pain VAS assesses the pain intensity experienced by the participant on a 100 millimeter (mm) VAS, where responses range from a response of no pain (score of 0 mm) to severest pain imaginable (score of 100 mm). The participant indicated the pain by marking the applicable place with slash (/) and the investigator then measured the length from left edge to the slash. | Baseline and Day 19 | 
| Rescue Doses | The immediate release (IR) oral opioids were used as rescue doses in the participants with lack of efficacy or to have relief from severe pain. In case of opioid-switching participants rescue doses were continued without any change in the preceding doses or the type throughout the study. The IR morphine HCl was used as the rescue dose for opioid-naive participants. The upper limit of rescue doses was specified for each daily dose of tapentadol PR. There was no change in the dose of rescue medication during maintenance period for opioid-naive participants. | Day 12, 13, 14, 15, 16, 17, 18 and 19 | 
| Number of Participants Who Discontinued Study Treatment Because of Any Adverse Event (AE) or Lack of Efficacy | The AE is an undesirable or unwanted consequence that occurred during the course of the clinical trial, but not necessarily because of study drug.The AEs included the onset of new symptoms, worsening of the frequency or severity of the symptom compared with Baseline, and abnormal findings including abnormal laboratory test values in the diagnostic examination. The participants who discontinued because of lack of efficacy were those in which satisfactory analgesia was not maintained. | Baseline up to 7 days after last dose of study treatment | 
| Sleep Questionnaire Regarding Time to Sleep and Total Time Slept | The sleep questionnaire is a 4-item questionnaire evaluating the condition of the sleep of the participant on the previous night. The participants were asked about the time taken by them to fall asleep previous night after bedtime and the total time they slept during previous night. | Pre-dose (Day 1) and Day 20 | 
| Sleep Questionnaire Regarding Number of Awakenings | The sleep questionnaire is a 4-item questionnaire evaluating the condition of the sleep of the participant on the previous night . Participants were asked to provide the number of times they awoke at night. | Pre-dose (Day 1) and Day 20 | 
| Sleep Questionnaire Regarding the Quality of Sleep | The sleep questionnaire is a 4-item questionnaire evaluating the condition of the sleep of the participant on the previous night. Participants rated overall sleep quality on a scale ranging from excellent to very poor. | Pre-dose (Day 1) and Day 20 | 
| Patient's Global Impression of Change (PGI-C) | PGI-C is a participant rated instrument to measure participant's change in overall status of general condition including pain on a 7-point scale; range from 1 (very much improved) to 7 (very much worse). | Day 19 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Cancer, Tapentadol