A Study to Compare Oxycodone/Naloxone Prolonged Release Against Codeine/Paracetamol in the Treatment of Moderate to Severe Chronic Low Back Pain or Pain Due to Osteoarthritis
A Study to Compare Oxycodone/Naloxone Prolonged Release Against Codeine/Paracetamol in the Treatment of Moderate to Severe Chronic Low Back Pain or Pain Due to Osteoarthritis
The purpose of this study is to compare oxycodone/naloxone combination tablet and
 codeine/paracetamol tablets in the treatment of moderate to severe chronic low back pain or
 pain due to osteoarthritis.
This is a randomised, double-blind, double-dummy, parallel group, 12-week study to assess the
 efficacy and tolerability of oxycodone/naloxone compared to codeine/paracetamol tablets in
 the treatment of moderate to severe chronic low back pain or moderate to severe pain due to
 OA of the hip and /or knee.

 The screening period will be 3 - 7 days duration. If a subject meets all the screening
 criteria they may enter the Run-in Period.

 During the screening period subjects will continue to take their pre-study pain medication.

 The run-in period will be 7 - 14 days duration. During the run-in period subjects will
 continue to take their pre-study pain medication.

 Visit 3 will occur at the end of the Run-in Period (7-14 days after Visit 2). To qualify for
 entry into the treatment period of the study, subjects must have uncontrolled pain as shown
 by average daily pain scores of >5 on 4 of the last 7 days of the run in period.

 Eligible subjects will be randomised to either oxycodone/naloxone or codeine/paracetamol
 tablets. Subjects will receive double-blind study medication for up to 12 weeks.
Inclusion Criteria:

 1. Male or female subjects at least 18 years or older.

 2. Female subjects less than one year post-menopausal must have a negative urine
 pregnancy test recorded prior to the first dose of study medication, be non-lactating,
 and willing to use adequate and reliable contraception throughout the study. A highly
 effective method of birth control is 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, injectables, combined oral contraceptives, some IUDs, sexual
 abstinence or vasectomised partner.

 3. Subjects with a clinical diagnosis of degenerative or primary OA whose primary pain
 site is of the hip(s) and/or knee(s) and that require around-the-clock opioid therapy
 in which the diagnosis may be supported by evidence such as one of the following: MRI,
 CAT, arthroscopy or x-ray. The clinical imaging of OA may include one or more of the
 following features: joint space narrowing, degenerative changes, osteophyte formation
 or subchondral cysts. Subjects will identify the most painful joint (hip or knee) for
 documentation of OA. Pain measurement will be done at this joint only.

 4. Subjects with moderate to severe chronic low back pain e.g osteoarthritis, spinal
 stenosis, spondylolisthesis, failed back surgery, scoliosis, discogenic disorders such
 as herniated disc.

 5. Subjects who are currently receiving codeine/paracetamol combination tablets up to a
 maximum dose of 120 mg codeine per day or tramadol up to a maximum dose of 100 mg/day
 or dihydrocodeine / paracetamol tablets up to a maximum dose of 120 mg dihydrocodeine
 per day.

 6. Subjects willing and able to participate in all aspects of the core study, including
 use of oral medication, completion of subjective evaluations, attending scheduled
 clinic visits, completing telephone contacts, and compliance with protocol
 requirements as evidenced by providing written, informed consent.

 7. Subjects in which the pre-study, non-opioid analgesics, and all other concomitant
 medications, including those medications for the treatment of depression are
 anticipated to remain stable throughout the treatment phase of the study.

 Exclusion Criteria:

 1. Any history of hypersensitivity to oxycodone, naloxone, codeine, ibuprofen, bisacodyl
 or related products and ingredients.

 2. Any contraindication to oxycodone, naloxone, codeine, paracetamol or ibuprofen.

 3. Subjects with evidence of significant structural abnormalities of the GI tract (e.g.,
 bowel obstruction, strictures) or any diseases/conditions that affect bowel transit
 (e.g., ileus, hypothyroidism).

 4. Subjects with cancer associated pain.

 5. Subjects with secondary osteoarthritis (e.g. fracture, septic, acromegaly etc.).

 6. Active alcohol or drug abuse and/or history of opioid abuse.

 7. Subjects with Rheumatoid Arthritis.

 8. Subjects with non opioid induced constipation.

 9. Subjects with evidence of clinically unstable disease, as determined by medical
 history, clinical laboratory tests, ECG results, and physical examination that, in the
 investigator's opinion, preclude entry into the study.

 10. Subjects with evidence of impaired liver/kidney function upon entry into the study
 defined as: Aspartate aminotransferase, alanine aminotransferase, or alkaline
 phosphatase levels >3 times the upper limit of normal; Gamma glutamyl transpeptidase
 ≥5 times the upper limit of normal; Total bilirubin level outside of the reference
 range unless the value is associated with pre documented Gilbert's Syndrome;
 Creatinine level outside of the reference range or > 2 mg/dl unless after discussion
 with the Medical Monitor it is confirmed the subject does not have renal impairment
 that would preclude the subject's inclusion in the study; In the investigator's
 opinion the subject has liver and/or kidney impairment to the extent that the subject
 should not participate in this study.

 11. Subjects who have required treatment for the diagnosis of IBS.

 12. Subjects receiving hypnotics or other CNS depressants that, in the investigator's
 opinion, may pose a risk of additional CNS depression with opioid study medication.

 13. Subjects with a history of depression or other psychiatric disorder that in the
 opinion of the investigator is significant enough to exclude the subject from the
 study.

 14. Subjects who are currently involved in legal action regarding their pain condition or
 subjects in which their pain condition may be of a psychiatric nature.

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

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

 17. Surgery within 2 months prior to the start of the Screening Period, or planned surgery
 during the12-week treatment period that may affect GI motility or pain levels.

 18. Subjects who have received a new chemical entity or an experimental drug within 30
 days of study entry (define as the start of the Screening Period).