| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic, moderate to severe osteoarthritis pain of the hip and/or knee. |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 5.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10031161 |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the long-term efficacy and safety of Norspan® versus placebo Norspan in subjects with chronic, moderate to severe osteoarthritis pain of the hip and/or knee. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Males and females more than 40 years of age (women of child bearing potential must have a negative pregnancy test, be non-lactating, and willing to use adequate and reliable contraception (defined as IUD, hormonal, condom + spermicide) throughout the study).
2. Clinical Diagnosis of OA of the hip and/or knee including fulfillment of the American College of Rheumatology Criteria (ACR-criteria) and Grade II-IV radiographic evidence within the past 1 year and pain from the relevant joint(s) for 1 year or longer (Appendix E).
3. Subjects with moderate to severe pain due to OA, despite their current therapy, as confirmed by a Western Ontario and McMaster Universities (WOMAC) OA Index (version LK 3.1) Section A, question 1 (’How much pain have you had when walking on a flat surface?’) answer of ’Moderate’, ’Severe’ or ’Extreme’ recorded at the Baseline Visit (Visit 2).
4. Subjects’ current OA therapy must include NSAID or COX-2 inhibitor therapy at a frequency and dose (defined as corresponding to at least half of the maximum daily allowed dose) that has been stable for at least 1 month prior to the Screening Visit (Visit 1).
5. Subjects must be willing to continue their treatment with NSAID or COX-2 inhibitor until the end of the Double-Blind Phase at a stable frequency and dose.
6. Subjects whose OA treatment includes non-opioid analgesics (other than NSAIDs, COX-2 inhibitors or aspirin for cardiovascular indications) or intermittent use of low-potent opioids (e.g. tramadol) must be willing to discontinue this regimen from the Screening Visit until the Completion/Discontinuation Visit and take Sponsor provided Paracetamol tablets as intermittent analgesic rescue.
7. Subjects receiving transcutaneous nerve stimulus (TENS) or biofeedback prior to study entry must be willing to discontinue this therapy for the duration of the study.
8. Subject must be willing to be contacted by telephone at specified times during the study and record daily information in a subject diary.
9. Subject must be able to read and comprehend national language, have access to a telephone and be willing to sign informed consent. |
|
| E.4 | Principal exclusion criteria |
1. Subjects treated with high-potent opioid analgesics (e.g. Durogesic®, OxyContin®, methadone) for their OA pain.
2. Subjects treated regularly with low-potent opioids analgesics (e.g. tramadol) for longer than 3 weeks prior to the Screening Visit.
3. History of chronic condition(s), in addition to OA, requiring frequent analgesic therapy (e.g. frequent headaches, frequent migraine, gout, rheumatoid arthritis).
4. Scheduled for surgery of the disease site (e.g. major joint replacement surgery), or any other major surgery that would fall within the Screening Phase or Double-Blind Phase of the study.
5. Clinically significant respiratory disease, cardiac disease, dysfunction of the biliary tract, thyroid disease, adrenal cortical insufficiency, prostatic hypertrophy or renal stricture, or any other medical condition, that, in the opinion of the Investigator, precludes entry into this study.
6. Indication of impaired liver function at screening (i.e. ≥ 3 times the upper limit of normal for ALAT), or in the opinion of the Investigator, liver function impairment to the extent that the subject should not participate in this study.
7. Indication of impaired kidney function at Screening (i.e. serum creatinine > 177 µmol/L).
8. Substance or alcohol abuse, or subjects who, in the opinion of the Investigator, have demonstrated addictive or substance abuse behaviours.
9. Patients with cancer (except basal cell carcinoma) or history of cancer in the last 5 years (except treated basal cell carcinoma).
10. 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.
11. Dermatological disorder at any relevant patch application site that precludes proper placement and/or rotation of patch placement.
12. Prior participation in a buprenorphine TDS study or current treatment with buprenorphine.
13. Steroids (oral, intra-muscular, intra-venous, intra-articular, epidural, or other corticosteroid injections) in the 6 weeks prior to Screening Visit or during the study. Subjects requiring steroid treatment will be removed from the study.
14. Patients, who are currently taking monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 2 weeks of entering the study.
15. Patients, who are currently taking hypnotics or other central nervous system depressants that, in the Investigator's opinion, may pose a risk of additional CNS depression with opioid study medication.
16. Patients, who are currently taking adjuvant analgesics such as antidepressants (e.g. amitriptyline, amoxapine, clomipramine, selective serotonin re-uptake inhibitors (SSRIs)) and anti-convulsants (e.g. gabapentin, tiagabine).
17. Participation in a clinical research study involving a new chemical entity within 3 months of study entry.
18. Allergies or other contraindications to transdermal systems or patch adhesives.
19. Known hypersensitivity (allergic reaction) to opioids or Paracetamol.
20. Ongoing requirement for and treatment with direct external heat sources such as heat lamps, electric blankets, saunas, heating pads and heated waterbeds.
21. New physiotherapy regimen scheduled to commence during the Double Blind Phase of the study.
22. Patients, who cannot or will not cut the hair at the patch site for proper placement of the patch.
23. Patients, who are unsuitable for any other reason to receive study medication in the opinion of the Investigator.
24. Congenital Long QT Syndrome or any family member with this condition.
25. Class IA anti-arrhythmic medications (e.g. quinidine, procainamide, disopyramide).
26. Class III anti-arrhythmic medications (e.g. sotalol, amiodarone, dofetilide).
27. Unstable, active or symptomatic: congestive heart failure, atrial fibrillation, myocardial ischemia, bradycardia. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Change in the WOMAC OA Index score for pain from Baseline Visit (Visit 2) to the end of the 6-month double-blind phase. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The primary analysis on ITT performed on primary endpoint after 6 months will be performed using Last Observation Carried Forward (LOCF) of data collected from at least one post dose observation. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
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