Targin for Non-cancer Pain
Targin for Non-cancer Pain
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)
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:

 1. Subjects continue to satisfy screening criteria outlined in the protocol

 2. Subject's OXY dose is between 10-50 mg/day

 3. 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

 4. Subjects who have constipation induced, or worsened by their opioid study medication,
 as shown by:

 1. 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

 2. The subjects' constipation was considered to be induced, worsened or maintained
 by their current study opioid medication and

 3. BFI value > 30.

 5. Subjects demonstrate compliance with laxative use, and completing appropriate and
 legible daily diaries

 6. 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:

 1. Females who are pregnant (positive β-hCG test) or lactating

 2. Any history of hypersensitivity or with any contraindication to oxycodone, naloxone,
 bisacodyl, or related products

 3. Subjects currently taking the equivalent of > 50 mg/day Oxycodone PR

 4. 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

 5. 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

 6. Subjects with evidence of significant structural abnormalities of the gastrointestinal
 tract or any diseases/conditions that affect bowel transit

 7. Subjects who have required treatment for the diagnosis of irritable bowel syndrome
 (IBS)

 8. 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

 9. 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

 10. Subjects diagnosed with cancer, not including basal cell carcinoma

 11. Subjects with Rheumatoid Arthritis (RA)

 12. Subjects receiving opioid substitution therapy for opioid addiction (e.g., methadone
 or buprenorphine)

 13. Subjects with active alcohol or drug abuse and/or history of opioid abuse

 14. 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)

 15. Subjects presently taking, or who had taken naloxone or naltrexone within 30 days of
 study entry (defined as the start of the Screening Period).