Targin for Non-cancer Pain

Study Overview
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Brief Summary
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To determine the improvement in symptoms of constipation in subjects receiving treatment with oxycodone/naloxone prolonged release tablets (OXN) compared to oxycodone prolonged release tablets (OXY) based on the Bowel Function Index (BFI)

Official Title
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A Randomized, Double-blind, Double-dummy, Parallel-group, Multicenter Study to Demonstrate Improvement in Symptoms of Constipation in Subjects With Moderate to Severe Non-malignant Pain Taking Oxycodone Equivalent of ≥10 mg/Day and ≤50 mg/Day as Oxycodone/Naloxone Prolonged-release (OXN) Compared to Subjects Taking Oxycodone Prolonged-release (OXY) Tablets Alone.

Conditions
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Non Cancer Pain

Intervention / Treatment
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* Drug: Oxycodone/naloxone prolonged release tablets


Participation Criteria
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Eligibility Criteria
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Screening Inclusion criteria: Males or females, 18 years of age or older Clinical diagnosis of musculo-skeletal pain for 4 weeks or longer with non-malignant pain etiology at Visit 1. Possible etiologies are conditions related to intervertebral disc disease, spondylolisthesis and osteoarthritis; other similar non-malignant diseases are also eligible. Patients with non-malignant pain that require around-the-clock opioid therapy (oxycodone equivalent of ≥10 mg/day and ≤50 mg/day) who are likely to benefit from WHO step III opioid therapy for the duration of the study Patients who have been already treated with NSAIDs at least 2 weeks before enrolment are also eligible, but they should rate their pain (Pain Intensity Scale -average pain over the last 24 hours) as ≥4 on 0-10 scale. Subjects are either taking opioid medication or willing to take opioids to treat their pain Patients who are willing to use adequate and reliable contraception throughout the study. Highly effective methods of birth control are defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilization, implants, injectable, combined oral contraceptives, some IUDs (intrauterine Device, hormonal), sexual abstinence or vasectomized partner Subjects willing and able to participate in all aspects of the study, including use of oral medication, completion of subjective evaluations, attending scheduled clinic visits, completing telephone contacts, and compliance with protocol requirements are evidenced by providing written informed consent Subjects taking pre-study, non-opioid analgesics, and all other concomitant medications, including those medications for the treatment of depression and are considered necessary for the subject's welfare, and are anticipated to remain stable throughout the double-blind period of the study, and are to be continued under the supervision of the investigator, are eligible. Patients who have been already treated with NSAIDs at least 2 weeks before enrolment are also eligible, but they should rate their pain (Pain Intensity Scale -average pain over the last 24 hours) as ≥4 on 0-10 scale. Criteria for entry to the Double-Blind phase: Subjects continue to satisfy screening criteria outlined in the protocol Subject's OXY dose is between 10-50 mg/day Subjects who rate their pain (Pain Intensity Scale -average pain over the last 24 hours) as≤4 on 0-10 scale with less than or equal to two doses of Morphine Sulfate tablets rescue medication per day for either the last three consecutive days or four of the last seven days Subjects who have constipation induced, or worsened by their opioid study medication, as shown by: The subject's medical need for regular intake of laxatives to have at least 3 bowel evacuations per week, or having less than 3 bowel evacuations per week when not taking a laxative, respectively and The subjects' constipation was considered to be induced, worsened or maintained by their current study opioid medication and BFI value > 30. Subjects demonstrate compliance with laxative use, and completing appropriate and legible daily diaries Subjects taking daily fibre supplementation or bulking agents are eligible if they can be maintained on a stable dose and regimen throughout the study, and in the investigator's opinion are willing and able to maintain adequate hydration. Screening Exclusion criteria: Females who are pregnant (positive β-hCG test) or lactating Any history of hypersensitivity or with any contraindication to oxycodone, naloxone, bisacodyl, or related products Subjects currently taking the equivalent of > 50 mg/day Oxycodone PR Evidence of clinically significant cardiovascular, renal, hepatic, gastrointestinal (paralytic ileus), or psychiatric disease, as determined by medical history, clinical laboratory tests, electrocardiogram (ECG) results, and physical examination, that will place the subject at risk upon exposure to the study medication or that could confound the analysis and/or interpretation of the study results Subjects with evidence of impaired liver/kidney function upon entry into the study defined as aspartate aminotransferase (AST; SGOT), alanine aminotransferase (ALT; SGPT), or alkaline phosphatase levels >3 times the upper limit of normal; gamma glutamyltranspeptidase (GGT or GGTP) ≥ 5 times the upper limit of normal; total bilirubin level outside of the reference range; and/or creatinine level outside of the reference range or >2 mg/dl, or in the investigator's opinion, liver and/or kidney impairment to the extent that the subject should not participate in this study Subjects with evidence of significant structural abnormalities of the gastrointestinal tract or any diseases/conditions that affect bowel transit Subjects who have required treatment for the diagnosis of irritable bowel syndrome (IBS) Subjects receiving hypnotics or other central nervous system (CNS) depressants that, in the investigator's opinion, may pose a risk of additional CNS depression with opioids study medication Surgery within 2 months prior to the start of the Screening Period, or planned surgery during the 12-week Double-blind Phase that may have affected GI motility or pain Subjects diagnosed with cancer, not including basal cell carcinoma Subjects with Rheumatoid Arthritis (RA) Subjects receiving opioid substitution therapy for opioid addiction (e.g., methadone or buprenorphine) Subjects with active alcohol or drug abuse and/or history of opioid abuse Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days of study entry (defined as the start of the Screening Period) Subjects presently taking, or who had taken naloxone or naltrexone within 30 days of study entry (defined as the start of the Screening Period).

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxycodone/naloxone prolonged release tablets<br>Dose strength:5/2.5 mg,10/5mg, 20/10mg,PO,q12h.daily dose from 10/5mg to 50/25mg.treatment duration:12 weeks | Drug: Oxycodone/naloxone prolonged release tablets<br> <br> |
| Active Comparator: Oxycodone prolonged release tablets<br>Dose strength:5mg,10mg, 20mg,PO,q12h.daily dose from 10mg to 50mg.treatment duration:12 weeks | Drug: Oxycodone/naloxone prolonged release tablets<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bowel function index(BFI) 12 Weeks |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modified BPI-SF-Average Pain over the last 24 hours |  | 12 weeks |