A Confirmatory Study of Fentanyl in Participants With Osteoarthritis or Low Back Pain

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate efficacy and safety of fentanyl in opioid-naive participants with osteoarthritis (disorder, which is seen mostly in older persons, in which the joints become painful and stuff) or low back pain who cannot obtain a sufficient analgesic effect by the treatment of non-opioid analgesics (drug used to control pain).

Detailed Description
-----------------
This is a multi-center (conducted in more than one center), double-blind (neither the participant nor the physician knows the assigned study drug), randomized (participants assigned study drug by chance), withdrawal study in opioid-naive participants with osteoarthritis or low back pain. The study will consist of titration period (10-29 days) and double-blind period (12 weeks) and the visits will include Day 5-7, 8, 15, 29 in titration period and Day 2-4, 8, 15, 22, 29, 43, 57, 71 and 85 in double-blind period. All the eligible participants will receive one-day adhesive transdermal patch (patch containing a drug that is put on the skin so the drug will enter the body through the skin) of either fentanyl at the dose ranging from 12.5 to 50 microgram per hour (mcg/hr) or matching placebo. Efficacy will be evaluated primarily by time to withdrawal due to insufficient analgesic efficacy. Participants' safety will be monitored throughout the study.

Official Title
-----------------
A Verification Study of JNS020QD in Patients With Osteoarthritis or Low Back Pain

Conditions
-----------------
Chronic Pain, Osteoarthritis, Low Back Pain

Intervention / Treatment
-----------------
* Drug: Fentanyl
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants whose pain because of osteoarthritis or low back pain is continuing for at least 12 weeks prior to informed consent Participants who are continuously taking a non-opioid analgesic at the normal highest dose or more for at least 14 consecutive days prior to informed consent, or participant at a certain dose (except the use on an as-needed base) on consecutive days Participants showing insufficient therapeutic efficacy of the non-opioid analgesic currently being used, and requiring a continuous opioid analgesic as per the investigator or sub-investigator Participants with an average pain intensity of 50 millimeter or more on the Visual Analog Scale (VAS) in 24-hour daily living prior to informed consent Participants who can be hospitalized to the 4th day after the initiation of titration period Exclusion Criteria: In cases of low back pain, participants with severe pain of lower extremities due to radiculopathy (a problem in which one or more nerves are affected) than that of low back pain, or participants with disc herniation (a medical condition affecting the spine due to trauma, lifting injuries, or idiopathic [unknown] causes) requiring an operation In cases of low back pain, participants with pain due to compression fracture Participants who had an operation that may affect the assessment within 30 days before informed consent Participants whose main cause of the pain to be assessed is considered attributable to psychogenic pain (physical pain that is caused, increased, or prolonged by mental, emotional, or behavioral factors) Participants with asthma, bradyarrhythmia (slow irregular heart beat) and severe respiratory function disorders

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fentanyl (Titration period)<br>One-day adhesive transdermal patch containing fentanyl (JNS020QD) applied to chest, abdomen, upper arm and thigh and replaced every day, starting at the dose of 12.5 microgram per hour (mcg/hr) for at least first 2 days, which will be increased by 12.5 mcg/hr at one time based on the medical examination of number of rescue treatments and visual analog scale (VAS) score of the participants. The dose will be increased up to maximum of 50 mcg/hr. The treatment will be continued for 10-29 days and then the eligible participants from this group will be randomly assigned to either of the two groups in the double-blind period. | Drug: Fentanyl<br>* One-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm or thigh and replaced every day.<br>|
| Experimental: Fentanyl (Double-blind period)<br>Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to fentanyl group, will be administered one-day adhesive transdermal patch containing fentanyl, applied to chest, abdomen, upper arm and thigh and replaced every day, the dose of which will be same as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment will be continued for 12 weeks. | Drug: Fentanyl<br>* One-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm or thigh and replaced every day.<br>|
| Placebo Comparator: Placebo (Double-blind period)<br>Participants meeting the pre-defined criteria for transfer from titration period to double-blind period and randomly assigned to placebo group, will be administered one-day adhesive transdermal placebo patch indistinguishable from fentanyl in appearance, applied to chest, abdomen, upper arm and thigh and replaced every day. The dose of fentanyl (from titration period) will be gradually decreased to prevent withdrawal symptoms and the dose of the matching placebo will be gradually increased up to same dose as the final application dose in the titration period (in the range of 12.5 to 50 mcg/hr). The treatment will continue for 12 weeks. | Drug: Placebo<br>* Placebo patch indistinguishable from one-day adhesive transdermal patch containing fentanyl 12.5 to 50 mcg/hr applied to chest, abdomen, upper arm or thigh and replaced every day.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time From the Initial Day of Application in Double-Blind Period to Withdrawal Because of Insufficient Analgesic Efficacy | Time from start of double-blind (researchers and participants were unaware of the treatment) period to withdrawal because of insufficient analgesic efficacy based on any of the pre-defined discontinuation criteria was noted. | Day 1 up to Day 85 (double-blind period) and Day 92 (discontinuation of the study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Visual Analog Scale (VAS) Score - Titration Period | The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a 100-millimeter (mm) VAS scale by drawing a slash. The left margin (0 mm) was considered No pain at all, and the right margin (100 mm) was considered Severer pain than this is inconceivable. The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of Screening period and during 3 days before the end of titration period was reported. | Day 12-14 (Screening period) and Day 27-29 (Titration period) | 
| Pain Visual Analog Scale (VAS) Score - Double-Blind Period | The intensity of average pain (degree of pain) felt by the participants in daily living throughout the day on a 100-millimeter (mm) VAS scale by drawing a slash. The left margin (0 mm) was considered No pain at all, and the right margin (100 mm) was considered Severer pain than this is inconceivable. The length (mm) from the left margin to the slash is measured. Mean VAS score during 3 days before the end of titration period and during 3 days before the end of double-blind period was reported. | Day 27-29 (Titration period) and Day 83-85 (double-blind period) | 
| Number of Participants Evaluated as Per Participant's Overall Assessment - Titration Period | The participant assessed his/her satisfaction with the therapeutic efficacy by the following 5 grades: Extremely satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied and Dissatisfied very much. The results were reported as Category 1 = At least Neither satisfied nor dissatisfied, which included participants with general evaluation of Extremely satisfied to Neither satisfied nor dissatisfied, and Category 2 = At least Satisfied, which included participants with general evaluation of Extremely satisfied to Satisfied. | Day 1 and 29 or final evaluation (Titration period) | 
| Number of Participants Evaluated as Per Participant's Overall Assessment - Double-Blind Period | The participant assessed his/her satisfaction with the therapeutic efficacy by the following 5 grades: Extremely satisfied, Satisfied, Neither satisfied nor dissatisfied, Dissatisfied and Dissatisfied very much. The results were reported as Category 1 = At least Neither satisfied nor dissatisfied, which included participants with general evaluation of Extremely satisfied to Neither satisfied nor dissatisfied, and Category 2 = At least Satisfied, which included participants with general evaluation of Extremely satisfied to Satisfied. | Day 1 and 85 or final evaluation (double-blind period) | 
| Number of Doses of Rescue Treatment Per Day - Titration Period | If a breakthrough pain occurred or the analgesic efficacy became insufficient, a fast-acting oral morphine was administered. At such instances, one-time dose of the rescue treatment was administered as per the pre-defined criteria. During hospitalization, Investigator, Sub-investigator or Study Collaborator recorded in the medical record and during the out-patient period, the participants were instructed to describe the name of rescue treatment, date and time of treatment, and one-time dose in the participant's diary. The mean number of treatments per day at each assessment time was reported. | Day 1 and 29 or final evaluation (Titration period) | 
| Number of Doses of Rescue Treatment Per Day - Double-Blind Period | If a breakthrough pain occurred or the analgesic efficacy became insufficient, a fast-acting oral morphine was administered. At such instances, one-time dose of the rescue treatment was administered as per the pre-defined criteria. During hospitalization, Investigator, Sub-investigator or Study Collaborator recorded in the medical record and during the out-patient period, the participants were instructed to describe the name of rescue treatment, date and time of treatment, and one-time dose in the participant's diary. The mean number of treatments per day at each assessment time was reported. | Day 1 and 85 or final evaluation (double-blind period) | 
| Brief Pain Inventory Short Form (BPI-sf) Score - Titration Period | The BPI-sf total score is an average of the pain interference score (mean value for the nine BPI-sf questions [questions inquiring about the extent of interference with activities by pain, where the extent is ranked from 0 (does not interfere) to 10 (completely interferes)]) and pain subscale score (mean value for the scores for BPI-sf questions 3, 4, 5 and 6 [questions inquiring about the extent of pain, where the extent is ranked from 0 (no pain) to 10 (pain as bad as you can imagine)]). Total score ranges from 0 to 10 with higher values indicating more pain. | Day 1 and 29 or final evaluation (Titration period) | 
| Brief Pain Inventory Short Form (BPI-sf) Score - Double-Blind Period | The BPI-sf total score is an average of the pain interference score (mean value for the nine BPI-sf questions [questions inquiring about the extent of interference with activities by pain, where the extent is ranked from 0 (does not interfere) to 10 (completely interferes)]) and pain subscale score (mean value for the scores for BPI-sf questions 3, 4, 5 and 6 [questions inquiring about the extent of pain, where the extent is ranked from 0 (no pain) to 10 (pain as bad as you can imagine)]). Total score ranges from 0 to 10 with higher values indicating more pain. | Day 1 and 85 or final evaluation (double-blind period) | 
| Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) - Titration Period | 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. | Day 1 and 29 or final evaluation (Titration period) | 
| Short-Form 36-Item Health Survey Version 2.0 (SF-36v2) - Double-Blind Period: | 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. | Day 1 and 85 or final evaluation (double-blind period) | 
| Number of Participants Evaluated as Per Physician's Overall Assessment - Titration Period | Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective. | Day 29 or final evaluation (Titration period) | 
| Number of Participants Evaluated as Per Physician's Overall Assessment - Double-Blind Period | Physician's global assessment of therapeutic efficacy (effectiveness) of the study drug was measured on a 2-point scale where 1 = effective and 2 = not effective. | Day 1 and 85 or final evaluation (double-blind period) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic pain, Osteoarthritis, Low back pain, Fentanyl, JNS020QD, Patch, transdermal, Opioid analgesics