AMZ001 for the Treatment of Knee Osteoarthritis Symptoms

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 4-week trial of a formulation of AMZ001 once or twice daily versus placebo twice daily, including a single-blind treatment group with a commercial gel four times daily.

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group, 4-week trial of a formulation of AMZ001 once or twice daily versus placebo twice daily, including a single-blind treatment group with a commercial gel four times daily. Participants will be evaluated for osteoarthritis by X-ray images of the knees and one knee will be selected for treatment as the target knee. The study gel will be applied directly to that knee throughout the 4 weeks of the study.

Eligibility Criteria:
Inclusion Criteria:

1. Osteoarthritis of the knee, according the American College of Rheumatology (ACR) clinical and X-ray criteria.
2. 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, after washout of any pain relief medication.
3. Women of child-bearing potential must use at least an acceptably effective method of contraception from enrollment up to at least 3 months after the study end.
4. Knee pain in the target knee for 14 days of the preceding month (knee pain due to osteoarthritis and not due to another condition such as bursitis, tendinitis, etc.) based on subject report.
5. On stable pain therapy (i.e., at least 3 days per week for the previous month) with an oral or topical NSAID prescribed by physician for 30 days prior to the Screening Visit and/or prescribed over-the-counter.
6. Except for osteoarthritis, in reasonably good health as determined by the Investigator.

Exclusion Criteria:

1. Known or suspected hypersensitivity to diclofenac, other non-steroidal anti-inflammatory drugs or related substances including aspirin, any of the components in either of the investigation products, or any physical impediment to gel application on the target knee.
2. Injection 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 oral/injected 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. Presence of an additional non-osteoarthritic disease affecting either knee, such as rheumatoid arthritis, psoriasis, gout or pseudo-gout, if there is reason to believe that the disease(s) may significantly interfere with the interpretation of the clinical response to the study drug.
7. Medical history of coronary artery bypass graft surgery.
8. Current cancer or treatment for cancer within the past five years, with the exception of non-melanoma skin cancer, unless affecting the target knee area.
9. Secondary osteoarthritis of the target knee, previous procedures or trauma affecting joint of the target knee.
10. Reported incidence of any of the following diseases: known osteoarthritis of the hip(s) if pain in hip(s) exceeds that of the target knee using the WOMAC Hip Pain subscore, presence of significant back pain, or at least one migraine attack within the past 12 months before screening, as reported by the subject.
11. Body Mass Index \> 45.0 kg/m2.
12. 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.
13. Known presence of a ulcer or any gastrointestinal bleeding within 6 months prior to screening.
14. Use of moderate or higher doses of opioid medication for the treatment of pain within 6 weeks before the screening visit.
15. Use of duloxetine, pregabalin, or gabapentin within 4 weeks before the screening visit.
16. History of alcohol or drug abuse within the past year prior to randomization.