Knee Osteoarthritis MedDRA version: 20.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859
Conditions
Interventions
Product Name: Diclofenac Gel AMZ001 3.06 %
Product Code: AMZ001
Pharmaceutical Form: Gel
INN or Proposed INN: AMZ001
Current Sponsor cod
Sponsors
Amzell BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subject is able to read and understand the language and content of the study material, understand the requirements for study visits, and is willing to provide information at the scheduled evaluations and appropriate written informed consent has been obtained. 2. Femorotibial osteoarthritis of the knee, according the American College of Rheumatology (ACR) clinical and radiographic criteria. 3. Radiological OA grade 1, 2, or 3 of the target knee, using the Kellgren-Lawrence method (KELLGREN & LAWRENCE 1957) as graded by central, independent reading of X-ray obtained during screening, or on a recent (within 6 months) X-ray image which fulfills the specifications for central reading. 4. Age between 40 years and 85 years at the time of screening, both included; of either sex. 5. Pain score rated on an 11-point numerical rating scale of the target knee of = 20 and = 45 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening. The subject should have undergone a washout-period of at least 5 half-lives of any analgesic medication before completing the screening questionnaire. 6. Women of child-bearing potential must use at least an acceptably effective method of contraception (progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action, male or female condom with or without spermicide, cap, diaphragm or sponge with spermicide). Postmenopausal status is defined as being amenorrheic for at least 1 year prior to screening. Sexually active men with a female partner of childbearing potential must agree to use condom from enrolment up to at least 3 months after the study end. 7. Knee pain in the target knee for 14 days of the preceding month (periarticular knee pain due to OA and not due to non-OA conditions such as bursitis, tendonitis, etc.) based on subject report. 8. On stable pain therapy (i.e., at least 3 days per week for the previous month) with an oral NSAID or acetaminophen/paracetamol prior to the Screening Visit. 9. Except for osteoarthritis, the subject is in reasonably good health as determined by the Investigator. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 290 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 150
Exclusion criteria
Exclusion criteria: 1. Known or suspected hypersensitivity to or previous hypersensitivity reactions to diclofenac, other non-steroidal anti-inflammatory drugs or related substances including aspirin, any of the excipients in either of the investigational products, or any physical impediment to gel application on the target knee. 2. Intra-articular delivery of corticosteroids or hyaluronic acid in the target knee within 6 months of screening or into any other joint within 30 days of screening. 3. High dose (equivalent to > 5 mg of prednisone/day) systemic corticosteroid treatment of more than 14 days during the past 6 months prior to screening. 4. Major surgery or arthroscopy of the target knee within the previous year prior to screening. 5. Planned surgery of the target knee within the next 3 months. 6. Use of a currently unapproved investigational drug, device or biologic within 6 months prior to screening. 7. Presence of concomitant non-osteoarthritic disease affecting either knee, such as rheumatoid arthritis, psoriasis, gout or pseudogout, if there is reason to believe that the disease(s) may significantly interfere with the interpretation of the clinical response to the study drug. 8. Medical history of coronary artery bypass graft surgery. 9. Current malignancy or treatment for malignancy within the past five years, with the exception of non-melanoma skin cancer, unless affecting the target knee area, or carcinoma in situ events. 10. Any other abnormal laboratory results or significant medical conditions that the Investigator believes should preclude the subject's participation in the trial. 11. Secondary osteoarthritis of the target knee, previous procedures or trauma affecting joint homeostasis including total meniscectomy or septic arthritis, or any other serious condition leading to secondary OA of the target knee. 12. Reported incidence of any of the following diseases: known osteoarthritis of the hip(s) if pain in either or both hip(s) exceeds that of the target knee using the WOMAC Hip Pain subscore, presence of significant radicular back pain, or at least one migraine attack within the past 12 months before screening, as reported by the subject. 13. Presence of severe pain in either knee, defined as > 45 out of 50 in response to the WOMAC pain sub-score (5 questions), at the time of screening, regardless of the eligibility of the contralateral knee. 14. Body Mass Index > 45.0 kg/m2. 15. Estimated glomerular filtration rate < 30 mL/min using the Modification of Diet in Renal Disease (MDRD) method. 16. Generalized skin irritation, previous skin reactions upon use of topical NSAIDs, current skin irritation or redness at the planned site of gel application, or significant skin disease including psoriasis, as judged by the investigator. 17. Known presence of gastroduodenal ulcer or any gastrointestinal bleeding (except hemorrhoidal) within 6 months prior to screening. 18. Use of any topical medication on the planned application site within 15 days of the time of randomization. 19. Use of moderate or higher doses of opioid medication for the treatment of pain within 6 weeks before the screening visit. 20. Use of duloxetine, pregabal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the change in pain intensity, in terms of the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) pain score of the target knee ; Secondary Objective: - To evaluate changes in symptoms of OA - To evaluate the changes in physical functioning - To evaluate administration regimens of AMZ001 - To evaluate the safety and tolerability of AMZ001 - To evaluate changes in quality of life ;Primary end point(s): The primary endpoint of this trial is the change from baseline in WOMAC pain sub-score (questions 1 to 5) in the target knee as evaluated at week 4.;Timepoint(s) of evaluation of this end point: From baseline to week 4. Subjects will fill in the WOMAC questionnaire in all the visits (from the screening visit to visit 6). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Changes from baseline in WOMAC total score and the WOMAC function and stiffness scores at week 4 - Changes from baseline in constant and intermittent OA pain assessed by ICOAP scores at week 4 - Changes from baseline in WOMAC pain weight-bearing score (questions 1, 2, and 5) and non-weight bearing score (questions 3 and 4) at week 4 - Changes from baseline in physical function assessed by the chair-stand test at week 4 - OMERACT-OARSI responder rate at week 4 - Total dose of rescue medication calculated as the sum of tablets used, based on pill counts - Time between baseline and first use of rescue medication - Change from baseline in WOMAC pain sub-score (questions 1 to 5) between groups receiving AMZ001 QD and BID in the target knee as evaluated at week 4 - Changes from baseline in constant and intermittent OA pain assessed by ICOAP scores between groups receiving AMZ001 QD and BID at week 4 - Changes from baseline in WOMAC pain weight-bearing score (questions 1, 2, and 5) and non-weight bearing score (questions 3 and 4) between groups receiving AMZ001 QD and BID at week 4 - Changes from baseline in physical function assessed by the chair-stand test between AMZ001 QD and BID at week 4 - Changes from baseline in WOMAC total score and the WOMAC function and stiffness scores between AMZ001 QD and BID at week 4. - Changes from baseline in the impact of OA on daily living as assessed by the Patient Global Assessment (PGA) score at week 4 - Changes from baseline in work productivity and activity assessed by the WPAI at week 4 - Changes from baseline in quality of life assessed by the EQ5D at week 4 ;Timepoint(s) of evaluation of this end point: At week four. All the questionnaires and assessments will be filled i | — |
Countries
Czech Republic, Denmark, United States
Contacts
Public ContactRegulatory Affairs Department
Nordic Bioscience Clinical Development
Outcome results
None listed