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
Condition: Osteoarthritis; Back Pain
MeSH terms: Osteoarthritis; Back Pain; Low Back Pain
Intervention: Oxycodone/Naloxone; Codeine/Paracetamol
Intervention description: 5/2.5, 10/5 and 20/10 mg oxycodone/naloxone combination, 12 hourly; 15/500 and 30/500 mg codeine/paracetamol tablets, 2 tablets 6 hourly
Intervention MeSH terms: Acetaminophen; Oxycodone; Codeine; Naloxone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 247.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Efficacy, tolerability, moderate/severe, oxycodone/naloxone; codeine/paracetamol, chronic low back pain, osteoarthritis

Summary:

      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.
    

Eligibility criteria:

        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).