Official Title: “A Randomised Double-Blind Multicentre Equivalence Study With Active Parallel Comparator Group to Evaluate the Efficacy and Safety of Norspan® Patches Versus Tramadol in Subjects With Chronic, Moderate to Severe Osteoarthritis Pain in the Hip, Knee &/or Lumbar Spine.”

The primary objective of this equivalence study is to evaluate the efficacy of Norspan® patches versus Tramadol in subjects with chronic, moderate to severe osteoarthritis pain of the hip and/or knee.

The secondary objectives are to evaluate the safety and general satisfaction for the patients in the two treatment groups.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2009

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 and/or knee, 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

Intervention(s) in this Clinical Trial

• Drug: Buprenorphine
• Drug: Tramadol

Primary Measures

• Equivalence study to evaluate the efficacy of Norspan® patches versus Tramadol in subjects with chronic, moderate to severe osteoarthritis pain of the hip and/or knee.

Secondary Measures

• To evaluate the safety and general satisfaction for the patients in the two treatment groups.

Inclusion Criteria:

• 1. 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 60 years or more with osteoarthritis in lumbar spine without nerve root pressure.
• 2. 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.
• 3. 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).
• 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.
• 5. 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).
• 6. Subjects must be able to read and comprehend Danish and be willing to sign informed consent.
• 7. Subjects must be willing and able to fill in a Subject Diary on a daily basis.

Exclusion Criteria:

• 1. 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.
• 2. 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.
• 3. 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.
• 4. 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.
• 5. 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.
• 6. Substance or alcohol abuse, or subjects who, in the opinion of the Investigator, have demonstrated addictive or substance abuse behaviour.
• 7. Subjects with cancer (except basal cell carcinoma) or history of cancer in the last 5 years (except treated basal cell carcinoma).
• 8. 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.
• 9. Dermatological disorder at any relevant patch application site that precludes proper placement and/or rotation of patch placement.
• 10. 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.
• 11. Intra-articular hyaluron acid injections given within 6 months prior to the Pre-screening Visit and during the study.
• 12. Any joint evacuation carried out within 6 weeks prior to the Pre-screening Visit and during the study.
• 13. Subjects who are currently taking monoamine oxidase inhibitors (MAOIs) or have taken
• MAOIs within 2 weeks prior to the Pre-screening Visit.
• 14. Participation in a clinical research study involving a new chemical entity within 3 months prior to the Pre-screening Visit.
• 15. Allergies or other contraindications to transdermal systems or patch adhesives.
• 16. Known lack of tolerance and/or effect of Tramadol.
• 17. Known hypersensitivity (allergic reaction) to opioids or Paracetamol.
• 18. Ongoing requirement for and treatment with direct external heat sources such as heat lamps, electric blankets, saunas, heating pads and heated waterbeds.
• 19. 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.
• 20. Subjects who cannot or will not cut the hair at the patch site for proper placement of the patch.
• 21. Any other contraindications listed in the Summary of Product Characteristics for
• Norspan® patches or Tramadol.
• 22. Subjects, who are unsuitable for any other reason to participate in the study in the opinion of the Investigator.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Norpharma A/S

Overall Clinical Trial Officials and Contacts

Dorthe Tvinnemose, DVM Study Director Norpharma A/S, Slotsmarken 15, DK-2970 Hoersholm, Denmark  

Overall Contact: Jill - Kiteley  info@contact-clinical-trials.com

Information obtained from ClinicalTrials.gov on October 15, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00426647

Study ID Number: BUP4006

ClinicalTrials.gov Identifier: NCT00426647

Health Authority: Denmark: The Regional Committee on Biomedical Research Ethics