A Study to Compare Safety and Efficacy of Osmotic Release Oral Syytem (OROS) Hydromorphone Hydrochloride (HCl) With Morphine Sustain Release (SR) 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 effectiveness and safety of Osmotic Release Oral System (OROS) hydromorohone Hydrochloride (HCl) compared with morphine sustain release (SR) in participants with chronic (lasting a long time) malignant (cancerous) cancer pain.

Detailed Description
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This is an open-label (all people know the identity of the intervention), multi-center (when more than 1 hospital or medical school team work on a medical research study), active-controlled, randomized (the study drug is assigned by chance) study to evaluate safety and efficacy of OROS extended-release (ER) hydromorhone HCl compared to twice daily morphine SR, in Taiwan participants with cancer pain. The study consists of 3 phases: Screening phase (14 days before administration of study drug), Dose titration phase (3 to 14 days) and Dose maintenance phase (14 days). This study will include 8 visits (Visit 1 [Day 1], Visit 2 [Day 1-13 telephonic], Visit 3 [Day 14], Visit 4 [Day 15 to Day 21 telephonic], Visit 5 [Day 22], Visit 6 [Day 23 to 27 telephonic] and Visit 7 [Day 28]). In dose titration phase, participants will be randomly assigned to 1 of the 2 treatments, OROS hydromorphone or morphine SR and dose of study medication will be adjusted every 48 hours at Investigator's discretion according to participant's analgesic (drug used to control pain) requirements. Morphine HCl will be used as rescue medication (maintained at 3 doses per day or less) for breakthrough pain. Participants primarily will be evaluated for equivalence of efficacy using the worst pain item of the brief pain inventory (BPI). Participants' safety will be monitored throughout the study duration.

Official Title
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A Randomized, Open-Labeled, Multi-Center Study to Investigate the Safety and Efficacy of OROS Hydromorphone HCl Comparing With Morphine SR in Cancer Pain Patients

Conditions
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Cancer Pain

Intervention / Treatment
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* Drug: Hydromprphone Hydrochloride (HCl) OROS
* Drug: Morphine Sustain Release (SR)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with cancer pain and experiencing inadequate pain control on or approaching Step 2 of the World Health Organisation (WHO) analgesic ladder Participants with pain scores greater than and equal to 4 on the average in the last 24 hours Participants requiring or are expected to require not more than 540 milligram of oral morphine or morphine equivalent every 24 hours for the management of chronic cancer pain Participants who can reasonably be expected to achieve stable dose of opioid study medication for the duration of the trial Participants who can reasonably be expected to achieve stable dose of opioid study medication for the duration of the trial Exclusion Criteria: Participants with pure or predominantly neuropathic pain or pain of unknown origin (where a mechanism or physical cause cannot be identified) Participants with acute pain or who have pain on movement Participants who have received a fentanyl patch within the last 5 days Participants intolerant or hypersensitive to hydromorphone or other opioids agonists (chemical substance capable of activating a receptor to induce a full or partial response) Participants with recent past history (within the previous 5 years) or current history of drug abuse or alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydromprphone Hydrochloride (HCl) OROS<br>Participants will receive hydromorphone HCl OROS 8 milligram (mg) every 24 hours, for 3 to 14 days of titration phase. Hydromorphone HCl OROS will be continued as per Investigator's discretion for next 14 days of maintenance phase. | Drug: Hydromprphone Hydrochloride (HCl) OROS<br>* Participants will receive hydromorphone HCl OROS 8 milligram (mg) every 24 hours, for 3 to 14 days of titration phase. Hydromorphone HCl OROS will be continued as per Investigator's discretion for next 14 days of maintenance phase.<br>|
| Active Comparator: Morphine Sustain Release (SR)<br>Participants will receive morphine SR 8 mg every 24 hours, for 3 to14 days of titration phase. Morphine SR will be continued as per Investigator's discretion for next 14 days of maintenance phase. | Drug: Morphine Sustain Release (SR)<br>* Participants will receive morphine SR 8 mg every24 hours, for 3 to14 days of titration phase. Morphine SR will be continued as per Investigator's discretion for next 14 days of maintenance phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Inventory (BPI) Questionnaire Item 3 Worst Pain Score at Day 14 | The BPI is a questionnaire designed to assess the severity and impact of pain on quality of life. Total score ranges from 0=no pain to 10=extreme pain. BPI Questionnaire Item 3 Worst Pain will be assessed using the BPI questionnaire, score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). | Day 14 | 
| BPI Questionnaire Item 3 Worst Pain Score at Day 28 | The BPI is a questionnaire designed to assess the severity and impact of pain on quality of life. Total score ranges from 0=no pain to 10=extreme pain. BPI questionnaire Item 3 Worst Pain will be assessed using the BPI questionnaire, score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BPI Questionnaire Item 6 How Much Pain You Have Right Now Score | The BPI is a questionnaire designed to assess the severity and impact of pain on quality of life. Total score ranges from 0=no pain to 10=extreme pain. BPI questionnaire Item 6 how much pain you have right now will be assessed using the BPI questionnaire, score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). | Baseline, Day 14, Day 22 and Day 28 | 
| BPI Questionnaire Item Pain Intensity Score | The BPI is a questionnaire designed to assess the severity and impact of pain on quality of life. Total score ranges from 0=no pain to 10=extreme pain. BPI questionnaire Item Pain Intensity will be assessed using the BPI questionnaire, score ranges from 0 (no pain) to 10 (pain as bad as you can imagine). | Baseline, Day 14, Day 22 and Day 28 | 
| BPI Questionnaire Item Pain Relief Score | The BPI is a questionnaire designed to assess the severity and impact of pain on quality of life. Total score ranges from 0=no pain to 10=extreme pain. BPI questionnaire Item Pain Relief will be assessed using the BPI questionnaire. Pain relief was rated on a scale ranging from 0% (no relief) to 100% (complete relief). | Baseline, Day 14, Day 22 and Day 28 | 
| BPI Questionnaire Item Pain Interference Score | The BPI is a questionnaire designed to assess the severity and impact of pain on quality of life. Total score ranges from 0=no pain to 10=extreme pain. BPI questionnaire Item Pain Interference will be assessed using the BPI questionnaire. Pain interference of general activity, mood, walking ability, normal work, relationships with others, sleep, and enjoyment of life will be rated on a scale ranging from 0 (no interference) to 10 (complete interference). | Baseline, Day 14, Day 22 and Day 28 | 
| Patient's Global Assessment on Effectiveness | Participants will evaluate effectiveness by providing rating on the question 'what is your rating of the overall effectiveness of the study medication during the titration or maintenance phase using 5-point scale ranging from 1 to 5, where 1=poor,. 2=fair, 3=good, 4=very good and 5=excellent. | Day 14, Day 22 and Day 28 | 
| Investigator's Global Assessment on Effectiveness | Investigator will evaluate effectiveness by providing rating on the question 'what is your rating of the overall effectiveness of the study medication during the titration or maintenance phase using 5-point scale ranging from 1 to 5, where 1=poor,. 2=fair, 3=good, 4=very good and 5=excellent. | Day 14, Day 22 and Day 28 | 
| Number of Times the Pain Medication Required for Breakthrough Pain | The requirement of breakthrough pain medication will be recorded by participants. Morphine HCl, 10 mg, will be used as rescue medication for breakthrough pain. | Baseline up to Day 28 | 
| Mean Total Daily Dose (TDD) of Study Medication | Mean total daily dose of study medication taken during study will be recorded by participants. | Baseline up to day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Hydromorphone hydrochloride OROS, Morphine