OXN PR Compared to OXY PR in Subjects With Postoperative Pain After Knee Arthroplasty

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that treatment with OXN PR tablets is non inferior to treatment with OXY PR tablets in terms of analgesic efficacy in patients with postoperative pain after knee arthroplasty based on average pain intensity scores.

Official Title
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A Randomised, Double-blind, Parallel Group Multicentre Study to Demonstrate Non-inferiority of the Analgesic Efficacy of Oxycodone/Naloxone 10/5 or 20/10 mg Prolonged Release Tablets (OXN PR) BID Compared to Oxycodone 10 or 20 mg Prolonged Release Tablets (OXY PR) BID in Subjects With Postoperative Pain After Knee Arthroplasty

Conditions
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Post Operative Pain

Intervention / Treatment
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* Drug: Oxycodone/Naloxone PR 20/10mg or 10/5mg tablets
* Drug: Oxycodone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 18 - 75 years of age. Body mass index (BMI) 18 - 35 kg/m2. If female and less than one year post-menopausal: negative serum or urine pregnancy test (positive beta-human chorionic gonadotrophin test) at screening. using an adequate and highly effective method of contraception throughout the study. A highly effective method of contraception is defined as one with a failure rate of less than 1% per year when used consistently and correctly. Examples include sterilisation, implants, injectables, combined oral contraceptives, hormonal intra uterine devices, sexual abstinence or vasectomised partner. Confirmed diagnosis of osteoarthritis of the knee. Planned surgical arthroplasty on one knee. Planned postoperative epidural analgesia for approximately 48 hours. Anticipated requirement for daily opioid treatment after epidural analgesia for 2.5 days. Able to participate in the study and have given written informed consent. Exclusion Criteria: Females who are pregnant or lactating. Opioid use within 3 months before the start of the screening period. Stable treatment with analgesics in World Health Organisation (WHO) Step I (non-opioid analgesics) is allowed. History of laxative use to treat constipation within 3 months before the start of the screening period. History of chronic constipation. Concurrent rheumatoid arthritis. Planned bilateral arthroplasty or revision knee arthroplasty. History of moderate to severe hepatic impairment. History of moderate to severe respiratory depression with hypoxia or hypercapnia, chronic obstructive pulmonary disease, cor pulmonale, bronchial asthma, or any severe impairment of pulmonary function. History of uncontrolled hypothyroidism, Addison's disease (adrenal cortical insufficiency), psychosis, cholelithiasis, prostatic hypertrophy(with documented residual of over 100 ml after voiding), delirium tremens, pancreatitis, hypotension, uncontrolled hypertension, uncontrolled cardiovascular diseases, head injury, epileptic disorder or predisposition to convulsions, or treatment with monoamine oxidase inhibitors (concurrent or within 2 weeks of discontinuation). Contraindication to treatment with opioids. History of hypersensitivity to oxycodone, naloxone, or to any of the excipients of OXN PR tablets. History of non-opioid induced paralytic ileus. Previous or current history of drug abuse, including alcohol abuse or opioid abuse. Evidence of clinically unstable disease Receipt of an investigational medicinal product within 30 days before the start of the screening period. Galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Delayed gastric emptying. Severe renal impairment (i.e. creatinine clearance <10 mL/minute). Weight <50 kg.Inclusion Criteria:

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tablets Oxycodone Naloxone (OXN)<br>Oxycodone/Naloxone prolonged release 20/10mg or 10/5mg tabs twice a day (BID) for 2.5 days (total 5 dosages) | Drug: Oxycodone/Naloxone PR 20/10mg or 10/5mg tablets<br>* Oxycodone/Naloxone prolonged release 20/10mg or 10/5mg tabs twice a day (BID) for 2.5 days (total 5 dosages)or Oxycodone 20mg<br>|
| Active Comparator: Oxycodone<br>Oxycodone PR 20mg or 10mg (twice a day) BID for 2.5 days (total 5 dosages) | Drug: Oxycodone<br>* Oxycodone 20mg or 10mg BID for 2.5 days (total 5 dosages)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of 4 NRS Scores for 24 Hour Pain Intensity at Rest, Shown as Absolute Change From Baseline (i.e. a Decrease From the Baseline Value) | The primary efficacy variable was the 24hr pain intensity score at rest, on a Numerical Rating Scale (NRS), with 0 = no pain and 10 = worst possible pain. This was assessed 1 hour after dosing on Day 1 (evening only), Day 2(morning and evening) and Day 3 (morning only). The primary efficacy end point (absolute change from baseline) was analysed on the per protocol (PP) data. The mean of these scores is shown as a value that is a mean change (a decrease in pain score) from the baseline value. | Mean of 24 hour pain intensity (absolute change from baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Dose (mg) of Rescue Analgesia for the Treatment Phase for Subjects Taking 20/10mg OXN PR Tablets or 20mg OXY PR Tablets | To compare the use of rescue analgesia for the 2 groups (OXN 20/10mg tablets and OXY 20mg tablets) during the double blind treatment phase. Rescue medication was given (OXY Immediate Release, 5mg capsules) if the subjects pain score on the (Numeric Rating Scale (NRS), 0 (no pain) to 10 (worst possible pain)), was greater than or equal to 4. The value presented is the mean dose over the double blind phase. | Mean dose during the whole double blind treatment phase (2.5 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oxycodone, Naloxone, Postoperative pain, Arthroplasty, Efficacy