An Efficacy and Safety Study of Hydromorphone Oral Osmotic System (OROS) in Korean Participants With Cancer Pain

Study Overview
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Brief Summary
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The purpose of this is study to evaluate improvement of sleep disorder caused by cancer pain after the administration of Hydromorphone Oral Osmotic System (OROS) in Korean participants with cancer.

Detailed Description
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This is an open-label (all people know the identity of the intervention), multi-center (conducted in more than 1 center), prospective (study following participants forward in time) dose-ascending study to evaluate the clinical usefulness of hydromorphone OROS in improvement of sleep disturbance caused by cancer pain.Total duration of study will be 3 weeks. The study consists of 3 phases: Screening phase (up to 1 week), Treatment phase (2 weeks), and Extension phase (12 weeks). The study will include 6 visits: Day -7, Day 1, Day 15, Day 43, Day 71, and Day 99. During screening phase, potential participants will receive strong oral (long acting) opioid analgesic (for 7 days) until Day 1 and the participants will be evaluated for participation in clinical study on Day 1. During treatment phase, participants will receive hydromorphone OROS (8 milligram [mg] to greater than or equal to 32 mg), once daily for 2 weeks, and the dose will be adjusted every 2 days from Day 3 at the Investigator's discretion and according to the strong oral (long acting) opioid analgesic administered from screening phase to Day 1 (the initial dose of the study drug will be determined by converting the dose of the previously administered analgesic to that of the daily dose of oral morphine with the equivalent analgesic effect to the study drug [dose with equivalent analgesic effect; Hydromorphone OROS dose: oral morphine dose =1:5]). Participants who completed treatment phase and suffer from continuing cancer pain will be enrolled to extension phase and study drug will be administered as per Investigator discretion for 99 days. Participants primarily will be evaluated for improvement in sleep disturbance measured by Korean Brief Pain Inventory (KBPI). Participants' safety will be monitored throughout the study.

Official Title
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Hydromorphone OROS in Korean Cancer Patients: Evaluation of Its Clinical Usefulness in Improvement of Sleep Disturbance

Conditions
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Cancer Pain

Intervention / Treatment
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* Drug: Hydromorphone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who are currently receiving strong opioid analgesic (drug used to control pain) for their cancer pain management Participants whose arithmetical mean of sleep disturbance caused by pain measured with Numeric Rating Scale for 3 days before Visit 2 (Day 1) is equal to or greater than 4 points Participants who are able, in the opinion of Investigator, to comply fully with the trial requirements including completion of the Korean-Brief Pain Inventory Participants who have signed an informed consent form Exclusion Criteria: Participants with pain who are not likely to response to opioid analgesics Participants who are intolerant or hypersensitive to hydromorphone Participants with the following digestive tract diseases which is serious enough to interfere action of an oral analgesic; diseases which can affect absorption and transit of oral drugs such as dysphagia (trouble swallowing), vomiting, no bowel movement, intestinal obstruction, serious intestinal stenosis (narrowing of a duct, tube, or 1 of the valves in the heart), etc Female participants of childbearing potential who are pregnant or lactating, seeking pregnancy, or failing to take adequate contraceptive precautions Participants in whom the risks of treatment with morphine/hydromorphone outweigh the potential benefits, including such risk categories as raised intracranial pressure, hypotension, hypothyroidism, asthma, compromised respiratory function compromised liver function, convulsive (an involuntary contraction or series of contractions of the voluntary muscles) disorder and Addison disease (disorder that occurs when the adrenal glands do not produce enough of their hormones)

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydromorphone OROS<br>Participants will receive hydromorphone OROS (8 milligram [mg] up to greater than or equal to 32 mg) once daily for 2 weeks, in a dose adjusted according to previously administered strong oral opioid analgesic (dose with equivalent analgesic effect; hydromorphone OROS dose: oral morphine dose=1:5) hydromorphone OROS will be continued as per Investigator's discretion for additional 84 days of extension phase. | Drug: Hydromorphone<br>* Participants will receive hydromorphone OROS (8 milligram [mg] to greater than or equal to 32 mg) once daily for 2 weeks, in a dose adjusted according to previously administered strong oral opioid analgesic (dose with equivalent analgesic effect; hydromorphone OROS dose: oral morphine dose=1:5) hydromorphone OROS will be continued as per Investigator's discretion for additional 84 days of extension phase.<br>* Other names: Jurnista;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Treatment Response in Sleep Disturbance Caused by Cancer Pain | Percentage of treatment response in sleep disturbance caused by cancer pain was reported. Treatment response in sleep disturbance was measured by Numeric Rating Scale (NRS) ranging from 0=no disturbance to 10=extreme disturbance. | Day 15 or Early withdrawal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep Disturbance Questionnaire: Analgesic Administration | The Investigator evaluated sleep disturbance through the participant's answers to below question in yes or no response: 'Did you need to take an analgesic for pain relief in order to go to sleep last night?' | Baseline and Day 15 | 
| Sleep Disturbance Questionnaire: Frequency of Waking Up | The Investigator evaluated sleep disturbance through the participant's answers to below question: How many times did you wake up while sleeping late night (frequency [once, 2 times, 3 times, 4 times, 5 times, couldn't fall asleep at all] of waking up due to pain last night). | Baseline and Day 15 | 
| Sleep Disturbance Questionnaire: Wake up Due to Unbearable Pain | The Investigator evaluated sleep disturbance through the participant's answers to below question in yes or no response: 'Did you wake up because of unbearable pain this morning?' | Baseline and Day 15 | 
| Korean Brief Pain Inventory (K-BPI) Questionnaire Score | K-BPI is a questionnaire designed to measure the degree of pain severity and the impact of pain in performing daily routines. K-BPI comprises of 9 items out of which 6 items were assessed. Score of each item ranges from 0 to 10, where 0=no pain/impact and 10=severe pain/impact. The 6 items that were assessed are: a) level of pain worst in last 24 hours; b) level of pain weakest in last 24 hours; c) level of pain average in last 24 hours; d) level of pain right now; e) how much pain reduced with the therapy taken; sixth item was further classified into 7 categories: i) general activities ii) mood iii) ambulatory ability iv) routine works v) interpersonal relation vi) sleep vii) life enjoyment. | Baseline and Day 15 | 
| Participant's Pain Intensity | Participant's pain intensity was measured using NRS ranging from 0=no pain to 10=unimaginable extreme pain. Participants maintained pain diary for 3 days before Baseline until Day 15 and pain intensity was measured twice daily (morning and afternoon). Here average pain intensity is reported. Average pain intensity was calculated as mean of morning pain intensity and evening pain intensity for each baseline and Day 15. | Baseline and Day 15 | 
| Number of Times the Short-Acting Opioid Analgesic Administered for Breakthrough Pain | The participants recorded the frequency of short acting opioid analgesic taken for treating breakthrough pain among the pains suffered by the participants. Here frequency means number of times the short-acting opioid analgesic administered for breakthrough pain from baseline to Day 15 | Baseline and Day 15 | 
| Number of Participants With Each Grade of Eastern Cooperative Oncology Group (ECOG) Performance Status Score | The ECOG performance status was used to evaluate participant's disease progression and the effect of the disease on the participant's activities of daily living. ECOG performance status score ranges from Grade 0 to 4, where Grade 0=Fully active, Grade 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, Grade 2=ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3=capable of only limited self-care, confined to bed or chair, and Grade 4=completely disabled. | Baseline and Day 15 | 
| Number of Participants With Clinical Global Impression-Improvement (CGI-Improvement) Score | The CGI-Improvement score evaluates how much the participant's condition is improved compared to Baseline. The score ranges from 1 to 7, where 1=improved very much, 2=Improved much, 3=Improved a little, 4=No change, 5=Aggravated a little,6=Aggravated much and 7=aggravated very much. | Day 15 | 
| Number of Participants in Each Category of Global Assessment of Overall Efficacy of Study Drug Assessed by Participants | Participants evaluated overall efficacy of study drug according to the rating of 1=not effective, 2=average, 3=effective, 4=very effective and 5=extremely effective. | Day 15 | 
| Number of Participants in Each Category of Global Assessment of Overall Efficacy of Study Drug Assessed by Investigators | Investigator evaluated overall efficacy of study drug according to the rating of 1=not effective, 2=average, 3=effective, 4=very effective and 5=extremely effective. | Day 15 | 
| Percentage of Participants Who Preferred the Oral Long-Action Opioids Analgesic or Study Drug | Participant's preferences between the oral long-action opioids analgesic and the study drug was reported. | Day 15 | 
| Percentage of Participants With Different Reasons for Their Preference for Oral Long-Action Opioids Analgesic or Study Drug | Participants reasons for preference between the long acting oral opioid analgesic and the study drug administered were reported. Reasonos for preferences were I experienced a certain pain relief effect during the administration of the drug, I didn't wake up due to pain while sleeping, It was more convenient because the number of administrations was reduced, I could reduce the administration of short acting narcotic analgesic to treat breakthrough pain and other. | Day 15 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer pain, Hydromorphone OROS, Jurnista