Open-Label Trial Comparing Oxycodone Medications

Study Overview
=================
Brief Summary
-----------------
The investigators hypothesize that subjects will have greater pain relief when taking IR-oxycodone compared with ER-oxycodone for several reasons. The ability to take a varying amount of medication at six different points over the course of a day will allow patients to take as much (or as little) medication as they need to control their pain. In addition, the ability to vary the medication doses in this way will give them a greater sense of control, which will also contribute to greater pain relief. Similarly, the investigators predict that patients will show greater benefits with IR-oxycodone on the measures of physical and emotional functioning. Because there is relatively little data on sleep apnea in chronic pain patients (Webster et al., 2008), these assessments are exploratory and not hypothesis-based. Finally, although it is typically thought that the abuse liability of IR-opioid medications is greater than for ER-medications, the data on which this belief are based have not involved systematic studies of patients with chronic pain; the assessments of abuse liability will therefore also be exploratory.

Detailed Description
-----------------
This study is a single-center, randomized, open-label, 13-week, 2-period crossover clinical trial. Subjects will complete each of the following (unless they withdraw from the trial): (1) a one-week baseline period during which the subject completes pain diaries and remains on stable dosages of their existing pain medications; (2) immediate-release (IR) oxycodone 5 mg 3-4 pills every four hours; (3) extended-release (ER) oxycodone 40 mg 1 pill every 12 hours and IR-oxycodone 5 mg 1-2 pills every six hours. Subjects will be randomized to one of two treatment sequences (ER-oxycodone first then IR-oxycodone or vice verse). It is expected that this trial will take approximately 2 years to complete. Crossover periods. Each of the two treatment periods will be 6 weeks in duration, which will allow ample time to assess pain relief, adverse effects, treatment satisfaction, and impact of treatment on health-related quality of life. There will be no need for a titration period at the beginning of either period or for a washout period before the second period because oxycodone at the same dosages will be administered in both periods. At each visit, subjects will be given sufficient medication to sustain them until at least the following visit.

Official Title
-----------------
Open-Label Trial Comparing Oxycodone Medications for Effectiveness and Satisfaction (OUTCOMES)

Conditions
-----------------
Chronic Pain

Intervention / Treatment
-----------------
* Drug: Extended Release Oxycodone
* Drug: Immediate Release Oxycodone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be at least 18 years old. Be able to read and understand English. Have a diagnosed chronic pain condition with pain every day or most days for the previous 6 months. Be receiving the equivalent of no more than 40-120 mg daily of an opioid analgesic that can be safely converted to oxycodone; this dosage includes all use of opioid analgesics, including for rescue and for breakthrough pain. Have an average daily pain rating for the baseline week of pain ratings equal to 4.0 or greater on a 0-10 numerical pain rating scale (NRS) of average pain intensity in the past 24 hours. Have completed at least 6 of the 7 daily diaries during the baseline week. Have at least 5 baseline week pain diary ratings equal to 3 or greater on the 0-10 NRS, with no more than one rating of 9 and no ratings of 10. Have stable concomitant use of all pain-related medications for 8 weeks prior to screening and being willing to continue stable use of these medications for the duration of the trial. Have the ability to either independently or with an accompanying person come to the research center for study visits. Exclusion Criteria: Treatment of their chronic pain with nerve blocks or any other interventional procedure within the past 8 weeks. A Beck Depression Inventory score < 27 at baseline or clinically significant depression or dementia that, in the opinion of the investigator, may interfere with a subjects' adherence to the study protocol and/or the accurate and consistent reporting of pain. History of suicide attempt within the past 2 years or current suicide plan or intent. History of excessive alcohol use or any illicit drug use within the past 2 years. Lack of adequate birth control in pre-menopausal women of child-bearing age and/or a positive urine pregnancy test, which will be performed on all women except those > 2 years post-menopausal or who have had a hysterectomy). History of malignancy within the past five years with the exception of successfully treated non-metastatic basal cell or squamous cell carcinomas of the skin.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ER Oxycodone vs IR Oxycodone<br>Extended release Oxycodone to assess pain relief adverse effects, treatment satisfaction and impact of treatment on health related quality of life. IR oxycodone will be distributed to subjects in 5 mg pills and they will be instructed to take 3-4 of these pills every four hours | Drug: Extended Release Oxycodone<br>* 40 mg tablets one to two every 12 hours, Immediate release 5mg pills 1-2 tablets every 6 hours<br>* Other names: Medication comparison;Drug: Immediate Release Oxycodone<br>* IR oxycodone will be distributed to subjects in 5 mg pills and they will be instructed to take 3-4 of these pills every 4 hours<br>* Other names: Medication comparison;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Numerical Pain Rating Scale (NRS) | The primary outcome measure for this clinical trial will be pain relief documented in the subjects' daily pain diaries. Specifically, the average of the daily pain ratings recorded by subjects during the final weeks of the two treatment periods will be compared. The treatment comparison of interest is IR-oxycodone vs. ER-oxycodone, which will be tested at the p < 0.05 level using a two-tailed test. | Daily | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Inventory | Will be administered to assess the extent to which chronic pain interferes with sleep and physical and emotional functioning. | Visits 2-6 | 
| Hospital Anxiety and Depression Scale | The HADS will be administered to assess anxiety and depression. | Visits 2-6 | 
| Short Form Health Survey (SF-36) | It is a 36-item questionnaire designed to measure general health related quality of life. | Visits 2, 4 and 6 | 
| Patient Global Impression of Change | This rating on a 7-point scale measures a patients overall assessment of change since starting a given treatment. This measure provides a subjects global assessment of change, presumably including change in pain, side effects, change in functional status, convenience of therapy, subject preference and values and overall satisfaction with the intervention. | Visits 4 and 6 the end of each of the two treatment periods | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic Pain, This clinical trial will compare immediate-release (IR), oxycodone and extended-release (ER) oxycodone in the, management of chronic pain