An Efficacy and Safety Study of Oral Osmotic Therapeutic System (OROS) Hydromorphone Hydrochloride (HCl) in Participants With Cancer Related Pain

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare the safety and efficacy of Oral Osmotic Therapeutic System (OROS) hydromorphone hydrochloride (HCl) with controlled-release oxycodone HCl in participants with cancer-related pain.

Detailed Description
-----------------
This is a double-blind (a medical research study in which neither the researchers nor the participants know what treatment the participants is receiving), randomized (study drug is assigned by chance), multi-center (when more than one hospital or medical school team work on a medical research study), comparative, parallel-group (a clinical trial comparing the response in two or more groups of participants receiving different treatments) study of OROS hydromorphone HCl compared with oxycodone HCl controlled-release in participants with moderate to severe cancer (abnormal tissue that grows and spreads in the body until it kills) pain. The study will consist of 3 phases: a screening period (up to 14 days before randomization), a dose titration phase (up to 8 days), and a dose maintenance phase (28 days). The study visits will be scheduled at weekly intervals. Eligible participants will be randomly assigned to receive either hydromorphone HCl once daily or oxycodone HCl twice daily (placebo will be administered when necessary for blinding). During titration phase, dosage of hydromorphone HCl or oxycodone HCl will be adjusted upward or downward to achieve stable pain control. It can be from 2 days to 8 days. Participants who complete dose titration will enter into the dose maintenance phase and will receive study treatment for 28 consecutive days. Morphine hydrochloride will be given as rescue analgesic (drug used to control pain) medication for breakthrough pain during the study. Primarily efficacy will be evaluated by measuring change in the score of Brief Pain Inventory (BPI) questionnaire item 'worst pain' at end of maintenance period. Participants' safety will be monitored throughout the study.

Official Title
-----------------
A Randomized, Double-Blind, Active Controlled, Multi-center Study to Investigate the Safety and Efficacy of OROS Hydromorphone HCl Once-daily Compared With Oxycodone HCL Controlled-release Twice Daily in Subjects With Cancer Pain

Conditions
-----------------
Pain

Intervention / Treatment
-----------------
* Drug: Hydromorphone HCl
* Drug: Oxycodone HCl CR
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants receiving strong oral or transdermal (through the skin) opioid analgesics with inadequate control of moderate to severe (very serious, life threatening) cancer pain or who presented with cancer pain and will be eligible to move to Step 3 of the WHO analgesic ladder when receiving weak opioids Participants who require or are expected to require between 40 mg and 184 mg of oral morphine or morphine equivalents every 24 hours for the chronic management of cancer pain Participants who are reasonably expected to achieve a stable dose of opioid study medication during the study Participants who are not expected to start a course of chemotherapy, radiotherapy, targeted cancer therapy, hormone therapy or diphosphates therapy after enrolment into the study. If participants are receiving long-term treatment including hormone therapy, target cancer therapy and diphosphate, the treatment should be kept stable as much as possible from 2 weeks before randomization and up to the completion of the study, encompassing the titration and maintenance phases Female participants who are premenarchal, postmenopausal, or surgically sterile, abstinent or if sexually active, they must use a medically acceptable method of contraception and must be willing to continue to use the same method of contraception throughout the study Exclusion Criteria: Participants with neuropathic pain or pain of unknown origin, or acute pain - Participants having pain only on movements Participants requiring other opioid analgesics (apart from morphine hydrochloride (HCl), in immediate release formulation, allowed as rescue medication for breakthrough pain) Participants with a recent history (within the previous 6 months) or current history of drug abuse or alcohol abuse Women of childbearing potential who were pregnant or lactating, seeking pregnancy or failing to use an adequate contraceptive method

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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: OROS Hydromorphone hydrochloride (HCl)<br>OROS Hydromorphone HCl will be administered in dose of 8, 16, 24, and 32 milligram (mg), once daily for 2 to 8 days of titrationphase and 28 days of maintenance phase. Starting dose will be based on participant's previous daily opioid dose. | Drug: Hydromorphone HCl<br>* Hydromorphone HCl will be administered in dose of 8, 16, 24, and 32 milligram (mg), once daily for 2 to 8 days of Titration phase and 28 days of Maintenance phase. Starting dose will be based on participant's previous daily opioid dose.<br>Drug: Placebo<br>* Placebo will be administered to the participants receiving hydromorphone HCl or oxycodone HCl CR along with the study treatment to maintain necessary blinding.<br>|
| Active Comparator: Oxycodone HCl Controlled release (CR)<br>Oxycodone HCl will be administered in dose of 10, 20, 30 and 40 mg, twice daily for 2 to 8 days of titrationphase and 28 days of maintenance phase. Starting dose will be based on participant's previous daily opioids dose. | Drug: Oxycodone HCl CR<br>* Oxycodone HCl will be administered in dose of 10, 20, 30 and 40 mg, twice daily for 2 to 8 days of titration phase and 28 days of maintenance phase. Starting dose will be based on participant's previous daily opioids dose.<br>Drug: Placebo<br>* Placebo will be administered to the participants receiving hydromorphone HCl or oxycodone HCl CR along with the study treatment to maintain necessary blinding.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Worst Pain in the Past 24 Hours Assessed by Brief Pain Inventory (BPI) Short Form Questionnaire Score at Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in worst pain in the past 24 hours in BPI score was reported. The total score ranges from 0 to 10, wherein 0 indicates no pain and 10 indicates pain as bad as participants could imagine. | Baseline and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pain at Its Least, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in pain at its least, in the past 24 hours in BPI score was reported. The total score ranges from 0 to 10, wherein 0 indicates no pain and 10 indicates pain as bad as participants could imagine. | Baseline and Day 29 | 
| Change From Baseline in Average Pain, in the Past 24 Hours Assessed by BPI Short Form Questionnaire Score at Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in average pain in the past 24 hours, in BPI score was reported. The score ranges from 0 to 10 wherein, 0 indicates no pain and 10 indicates pain as bad as participants could imagine. | Baseline and Day 29 | 
| Change From Baseline in Pain Right Now Assessed by BPI Short Form Questionnaire Score at Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. Change in Pain Right now in BPI was reported. The score ranges from 0=no pain to 10=pain as bad as participants could imagine. | Baseline and Day 29 | 
| Change From Baseline in Pain Relief, in the Past 24 Hour Recorded Assessed by BPI Short Form Questionnaire at Day 29 | The BPI is questionnaire for evaluating the degree of pain severity and the impact of pain in performing daily routines. BPI comprises of total 9 items in total, and the 8th item consisting of 7 sub-items is a question asking the degree of disturbance due to pain. The score ranges from 0% to 100%, wherein 0% indicates no relief and 100% indicates complete relief. | Baseline and Day 29 | 
| Breakthrough Pain Medication (Rescue Medication) Doses Taken | Any breakthrough pain medication taken during the overall study was reported. Morphine hydrochloride was used as a rescue medication in case of breakthrough pain. | Baseline up to Day 29 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pain, Hydromorphone hydrochloride, Oxycodone hydrochloride