Norspan® Patches Versus Tramadol in Subjects With Chronic, Moderate to Severe Osteoarthritis Pain in the Hip Knee and/or Lumbar Spine

This is a randomised, double-blind, multicentre equivalence study with active comparator, parallel group, to evaluate the efficacy and safety of Norspan® patches versus Tramadol in subjects with OA pain in hip, knee and/or lumbar spine, currently receiving sub-optimal analgesic treatment (defined as BS-11 score > 4) when treated with paracetamol 4000 mg/day or another analgesic at least comparable to this.

The study consist of 4 phases:

Run-in, Wash-out, Double blind and Follow-up

Inclusion criteria

• Males and females aged 18 years or more (women of childbearing potential must have a negative pregnancy test, be non-lactating, and willing to use adequate and reliable contraception (defined as IUD, contraceptive pill or depot gestagen) throughout the study) with osteoarthritis in the hip &/or knee.

Or Males & females aged 50 years or more with osteoarthritis in lumbar spine without nerve root pressure.

• Clinical diagnosis of OA in the hip and/or knee including fulfilment of ACR-criteria and radiographic or MR-Scan evidence for the primary OA-joint in hip &/or knee.

Or Clinical diagnosis of OA in the lumbar spine without nerve root pressure, & with radiographic or CT-scan evidence for lumbar OA.

• Subjects with moderate to severe pain confirmed by a BS-11 score > 4 for their pain on average in their primary OA-joint during the last 5 days prior to the Baseline Visit (Randomisation Visit/Visit 4).
• Subjects must previously or during Wash-out-Phase have been treated with 4000 mg Paracetamol IR daily or another analgesic treatment at least comparable to this and not have been adequately pain relieved (defined as BS-11 score > 4 for their pain on average in their Primary OA-joint during 5 continuous days) on that treatment.
• Subjects must be willing to discontinue all other analgesics (incl. glucosamine) at the Pre-Screening Visit (Visit 1) and until the Completion/Discontinuation Visit (Visit 10).
• Subjects must be able to read and comprehend Danish and be willing to sign informed consent.
• Subjects must be willing and able to fill in a Subject Diary on a daily basis.

Exclusion criteria

• Subjects treated with high-potent opioid analgesics (e.g. morphine, fentanyl, oxycodone, methadone, hydromorphone, ketobemidone, buprenorphine (incl. Norspan® patches)) for their OA pain. Except subjects treated with high-potent opioid analgesics for up to four continuous weeks for their OA pain beyond 3 months prior to the Pre-screening Visit.
• Subjects treated with high-potent opioid analgesics (e.g. morphine, fentanyl, oxycodone, methadone, hydromorphone, ketobemidone, buprenorphine (incl. Norspan® patches)) within four weeks prior to the Pre-screening Visit due to non-OA pain.
• Subjects treated with more than 200 mg Tramadol daily or 200 mg codeine daily during the last two weeks prior to the Pre-screening Visit.
• History of chronic condition(s), in addition to OA, requiring frequent analgesic therapy (e.g. frequent headaches, frequent migraine, gout, rheumatoid arthritis) and severe respiratory disease.
• Scheduled for surgery that would fall within all phases (Run-in-Phase, Wash-out-Phase, Double-Blind-Phase and Follow-up-Phase) of the study.
• Substance or alcohol abuse, or subjects who, in the opinion of the Investigator, have demonstrated addictive or substance abuse behaviour.
• Subjects with cancer (except basal cell carcinoma) or history of cancer in the last 5 years (except treated basal cell carcinoma).
• Untreated depression or other psychiatric disorder in such a way that participation in the study may, in the opinion of the Investigator, pose an unacceptable risk to the subject.
• Dermatological disorder at any relevant patch application site that precludes proper placement and/or rotation of patch placement.
• Treatment with steroids (oral, intra-muscular, intra-venous, intra-articular, epidural, or other corticosteroid injections) within 6 weeks prior to the Pre-screening Visit and during the study.
• Intra-articular hyaluron acid injections given within 6 months prior to the Pre-screening Visit and during the study.
• Any joint evacuation carried out within 6 weeks prior to the Pre-screening Visit and during the study.
• Subjects who are currently taking monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 2 weeks prior to the Pre-screening Visit.
• Participation in a clinical research study involving a new chemical entity within 3 months prior to the Pre-screening Visit.
• Allergies or other contraindications to transdermal systems or patch adhesives.
• Known lack of tolerance and/or effect of Tramadol.
• Known hypersensitivity (allergic reaction) to opioids or Paracetamol.
• Ongoing requirement for and treatment with direct external heat sources such as heat lamps, electric blankets, saunas, heating pads and heated waterbeds.
• New physiotherapy and/or chiropractic and/or other non pharmacological regimen scheduled to commence during the Run-in-Phase, Wash-out-Phase or Double-Blind-Phase of the study. This includes physiotherapy and/or chiropractic and/or other non pharmacological regimen not in a scheduled weekly window.
• Subjects who cannot or will not cut the hair at the patch site for proper placement of the patch.
• Any other contraindications listed in the Summary of Product Characteristics for Norspan® patches or Tramadol.
• Subjects, who are unsuitable for any other reason to participate in the study in the opinion of the Investigator.