A Dose-Finding Study of Fentanyl (JNS020 QD) 1-Day Transdermal Patch in Participants With Cancer Pain

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of fentanyl 1-day application (JNS020QD) transdermal patch (patch containing a drug that is put on the skin so the drug can enter the body through the skin) and to assess the non-inferiority of fentanyl 1-day application transdermal patch to fentanyl 3-day application (JNS005) transdermal patch in participants with cancer pain.

Detailed Description
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This is a multi-center (conducted in more than one center) study, consisting of two periods: Period 1 is open-label (all people know the identity of the intervention), non-comparative dose titration phase and Period 2 is double blind (neither physician nor participant knows the treatment that the participant receives), positive control (fentanyl 3-day application transdermal patch is used as control drug) phase. In Period 1, fentanyl 1-day application transdermal patch 12.5 microgram per hour (mcg/hr) will be applied to chest, abdomen, upper arm or thigh and will be maintained for 2 days to ensure the safety of participants. Dose escalation or reduction will be allowed based on participant's condition from Day 3 to Day 11 and thereafter dose will be maintained from Day 11 to Day 13 with a maximum application dose of 100 mcg/hr. The total duration of Period 1 is 14 days (a total of 13 applications; including the day of final patch removal). Participants who met the predefined criteria at the end of dose titration phase will enter the double blind phase. In double blind phase, participants will receive either fentanyl 1-day application transdermal patch and placebo matched to fentanyl 3-day application transdermal patch or fentanyl 3-day application transdermal patch and placebo matched to fentanyl 1-day application transdermal patch at the same dose as used at the completion of Period 1. The duration of Period 2 is 10 days. Efficacy will primarily be evaluated by percentage of participants achieving dose titration success and change in mean visual analog scale (VAS) score. Participants' safety will be monitored throughout the study.

Official Title
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A Phase II/III Study of JNS020QD in Cancer Pain Patients - A Dose-Finding, Double-Blind Study of JNS020QD Compared With JNS005 in Patients Previously Untreated With Opioid Analgesics

Conditions
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Pain, Cancer

Intervention / Treatment
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* Drug: Fentanyl 1-day transdermal patch (Titration Phase)
* Drug: Fentanyl 1-day transdermal patch (Double Blind Phase)
* Drug: Fentanyl 3-day transdermal patch (Double Blind Phase)
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with cancer pain who were previously not treated with opioid analgesics (drug used to control pain) Participants with a pain score of greater than or equal to 35 millimeter (mm) on a 100-mm visual analog scale (VAS) Participants who are considered to have insufficient response to non-opioid analgesics and require treatment with opioid analgesics by the physician Participants who have an established diagnosis of cancer and are notified of the disease Participants who can be hospitalized during Period 1 (dose-titration period) Exclusion Criteria: Participants with impaired respiratory function due to chronic lung disease or others Participants with asthma (breathing disorder in which there is wheezing and difficulty in breathing) Participants with bradyarrhythmia (slow, irregular heartbeats) Participants with following measurements indicative of hepatic or renal impairment during the pre-treatment observation period: Aspartate transaminase (AST) greater than 5 times the upper limit of reference range, Alanine transaminase (ALT) greater than 5 times the upper limit of reference range, serum creatinine greater than 3 times the upper limit of reference range Participants with any cerebral damage, such as brain tumor, accompanied by increased intracranial pressure, disturbance of consciousness, coma, or respiratory disturbance

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: Fentanyl 1-day transdermal patch (Titration Phase)<br>Fentanyl 1-day application transdermal patch releasing the drug at the rate of 12.5 microgram per hour (mcg/hr) applied once daily, and maintained for 2 days. Dose escalation or reduction is done as per Investigator's discretion (maximum applied dose is 100 mcg/hr) up to Day 11 and then dose is fixed up to end of treatment period, that is Day 14. Participants who met the predefined criteria at the end of Titration Phase enter the Double Blind Phase. | Drug: Fentanyl 1-day transdermal patch (Titration Phase)<br>* Fentanyl 1-day application transdermal patch releasing the drug at the rate of 12.5 mcg/hr applied once daily, and maintained for 2 days. Dose escalation or reduction is done as per Investigator's discretion (maximum applied dose is 100 mcg/hr) up to Day 11 and then dose is fixed up to end of treatment period, that is Day 14.<br>* Other names: JNS020QD;|
| Experimental: Fentanyl 1-day transdermal patch (Double Blind Phase)<br>Participants who meet the predefined criteria at the end of Titration Phase and enter the Double Blind Phase receive fentanyl 1-day application transdermal patch and placebo matched to fentanyl 3-day application (JNS005) transdermal patch applied once daily releasing the drug at the same dose as maintained at the end of Titration Phase with maximum applied dose of 100 mcg/hr for 10 days. | Drug: Fentanyl 1-day transdermal patch (Double Blind Phase)<br>* Fentanyl 1-day application transdermal patch applied once daily releasing the drug at the same dose as maintained at the end of Titration Phase with maximum applied dose of 100 mcg/hr for 10 days.<br>* Other names: JNS020QD;Drug: Placebo<br>* Placebo matching to fentanyl 3-day application transdermal patch applied once daily releasing the drug at the same dose as maintained at the end of Titration Phase for 10 days.<br>|
| Active Comparator: Fentanyl 3-day transdermal patch (Double Blind Phase)<br>Participants who meet the predefined criteria at the end of Titration Phase and enter the Double Blind Phase receive fentanyl 3-day application transdermal patch and placebo matched to fentanyl 1-day application transdermal patch applied once daily releasing the drug at the same dose as maintained at the end of Titration Phase with maximum applied dose of 100 mcg/hr for 10 days. | Drug: Fentanyl 3-day transdermal patch (Double Blind Phase)<br>* Fentanyl 3-day application transdermal patch applied once daily releasing the drug at the same dose as maintained at the end of Titration Phase with maximum applied dose of 100 mcg/hr for 10 days.<br>* Other names: JNS005;Drug: Placebo<br>* Placebo matching to fentanyl 1-day application transdermal patch applied once daily releasing the drug at the same dose as maintained at the end of Titration Phase for 10 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving Dose Titration Success | Participants achieving dose titration success included all participants who had a mean Visual Analog Scale (VAS) score of less than or equal to 34 millimeter (mm) and received not more than 2 rescue doses during the last 3 days before the completion or discontinuation of dose titration phase. Pain Intensity VAS measured severity of pain on a 100 mm scale ranging from 0 mm (no pain) to 100 mm (severest pain conceivable) and rescue dose was defined as dose of a fast-acting oral morphine hydrochloride solution or morphine in water solution used in the case of breakthrough pain. | Day 14 or early discontinuation (ED) | 
| Change From Dose Titration Phase in the Mean Visual Analog Scale (VAS) Score at Double Blind Phase | The mean VAS score for the last 3 days before the completion or discontinuation of Double Blind Phase was compared with that for the last 3 days before the completion or discontinuation of Dose Titration Phase and the change from Dose Titration Phase in the mean VAS Score at Double Blind Phase was reported. Pain Intensity VAS measured severity of pain on a 100 mm scale ranging from 0 mm (no pain) to 100 mm (severest pain conceivable). | Dose Titration Phase (Day 12 to Day 14) and Double Blind Phase (Day 8 to Day 10) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Response Based on Participant's Global Assessment Scale in Titration Phase | Participants were asked to assess their satisfaction with respect to the therapeutic efficacy (effectiveness) of the study drug to control pain on a 5-point scale ranging from 1 to 5, where 1 = extremely satisfied, 2 = satisfied, 3 = neither satisfied nor dissatisfied, 4 = dissatisfied and 5 = extremely dissatisfied. | Day 1 pre-application (PA), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13 and Day 14 or ED | 
| Number of Participants With Response Based on Participant's Global Assessment Scale in Double Blind Phase | Participants were asked to assess their satisfaction with respect to the therapeutic efficacy of the study drug to control pain on a 5-point scale ranging from 1 to 5, where 1 = extremely satisfied, 2 = satisfied, 3 = neither satisfied nor dissatisfied, 4 = dissatisfied and 5 = extremely dissatisfied. | Day 14-End of Titration Phase (ETP), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9 and Day 10 or ED | 
| Pain Intensity Visual Analog Scale (VAS) Score in Titration Phase | Participants were asked to assess their resting pain intensity (severity of pain) on a 100-mm VAS with the left edge (0 mm) defined as no pain and the right edge (100 mm) defined as severest pain conceivable. | Day 1 PA, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13 and Day 14 or ED | 
| Pain Intensity Visual Analog Scale (VAS) Score in Double Blind Phase | Participants were asked to assess their resting pain intensity (severity of pain) on a 100-mm VAS with the left edge (0 mm) defined as no pain and the right edge (100 mm) defined as severest pain conceivable. | Day 14-End of Titration Phase (ETP), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9 and Day 10 or ED | 
| Percentage of Participants Achieving Pain Control in Double Blind Phase | Pain control was assessed based on change in VAS and number of daily rescue doses during 3 days before completion of Double Blind Phase from 3 days before start of Double Blind Phase. For VAS score, difference of less than or equal to +15 mm and for rescue doses, difference of less than or equal to 1 was considered significant to achieve pain control. Pain Intensity VAS measured pain severity on a scale ranging from 0 mm (no pain) to 100 mm (severest pain conceivable) and rescue dose was defined as dose of fast-acting oral morphine formulation used in case of breakthrough pain. | Day 10 or ED | 
| Number of Participants With Pain Intensity Assessed by Categorical Scale for Pain in Titration Phase | Participants were asked to assess their resting pain intensity (severity of pain) on a 4-point categorical scale ranging from 0 to 3 where 0 = no pain, 1 = mild pain, 2 = moderate pain and 3 = severe pain. | Day 1 PA, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13 and Day 14 or ED | 
| Number of Participants With Pain Intensity Assessed by Categorical Scale for Pain in Double Blind Phase | Participants were asked to assess their resting pain intensity (severity of pain) on a 4-point categorical scale ranging from 0 to 3 where 0 = no pain, 1 = mild pain, 2 = moderate pain and 3 = severe pain. | Day 14-End of Titration Phase (ETP), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9 and Day 10 or ED | 
| Number of Participants With Total Duration of Pain Per Day in Titration Phase | The participants assessed total painful time in 1 day on a 5-point scale ranging from 0 to 4 where 0 = less than (<) 4 hours, 1 = greater than or equal to (>=) 4 hours to less than 8 hours, 2 = greater than or equal to 8 hours to less than 12 hours, 3 = greater than or equal to 12 hours and 4 = 24 hours (all day). | Day 1 PA, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13 and Day 14 or ED | 
| Number of Participants With Total Duration of Pain Per Day in Double Blind Phase | The participants assessed total painful time in 1 day on a 5-point scale ranging from 0 to 4 where 0 = less than (<) 4 hours, 1 = greater than or equal to (>=) 4 hours to less than 8 hours, 2 = greater than or equal to 8 hours to less than 12 hours, 3 = greater than or equal to 12 hours and 4 = 24 hours (all day). | Day 14-End of Titration Phase (ETP), Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9 and Day 10 or ED | 
| Mean Number of Rescue Doses in Titration Phase | Rescue dose was defined as dose of a fast-acting oral morphine hydrochloride solution or morphine in water solution used in the case of breakthrough pain or lack of analgesic effect. | Day 1 PA, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9, Day 10, Day 11, Day 12, Day 13 and Day 14 or ED | 
| Mean Number of Rescue Doses in Double Blind Phase | Rescue dose was defined as dose of a fast-acting oral morphine hydrochloride solution or morphine in water solution used in the case of breakthrough pain or lack of analgesic effect. | Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9 and Day 10 or ED | 
| Number of Participants With Response Based on Physician's Global Assessment Scale in Titration Phase | The treating physician assessed the therapeutic efficacy of the study drug to control pain on a 2-point scale of effective and ineffective. Number of participants with effective and ineffective therapeutic efficacy with respect to the study drug were reported. | Day 14 | 
| Number of Participants With Response Based on Physician's Global Assessment Scale in Double Blind Phase | The treating physician assessed the therapeutic efficacy of the study drug to control pain on a 2-point scale of effective and ineffective. Number of participants with effective and ineffective therapeutic efficacy with respect to the study drug were reported. | Day 10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Cancer, Fentanyl, JNS020QD, JNS005