Evaluation of the Safety and Efficacy of PENNSAID Gel in the Treatment of Osteoarthritis of the Knee

Subjects with OA of the knee who complete a washout of all pain medication will be randomized
to either a topical NSAID gel formulation (active study drug) or placebo. Study drug or
placebo will be applied twice a day to the osteoarthritic knee during a 4-week treatment
period. Subjects will receive acetaminophen for rescue medication as needed to treat pain
during the treatment period. Subjects will report pain intensity, drug application
information and use of rescue medication every day and complete the WOMAC LK3.1 OA Index and
a Patient Global Assessment at clinic visits. Safety assessments include adverse events, skin
irritation assessments, clinical laboratory tests, physical examinations and vital signs.

Inclusion Criteria:

1. Primary osteoarthritis of the knee

2. Radiologic evidence of OA of the knee

3. On stable pain therapy with an oral or topical NSAID or acetaminophen

4. Experience a "moderate flare" of pain following washout of stable pain therapy

5. Able to read and understand English or Spanish to answer pain assessment questions
without any explanation

6. If female, surgically sterile or non-pregnant

7. Except for OA, in reasonably good general health

8. Written informed consent

Exclusion Criteria:

1. Secondary OA of the study knee

2. History of pseudo gout or inflammatory flare-ups

3. Participation would conflict with contraindications, warnings or precautions as stated
in the prescribing information for oral or topical diclofenac

4. Severe, uncontrolled cardiac, renal, hepatic, or other systemic disease

5. Any malignancy within the previous 3 years, except local therapy for superficial skin
cancer not on the study knee

6. Known sensitivity to the use of oral or topical diclofenac, aspirin (acetylsalicylic
acid [ASA]) or any other NSAID, dimethyl sulfoxide (DMSO), or ethanol

7. Ongoing abnormality that could confound interpretation of the safety results (eg,
anemia, unresponsive gastrointestinal [GI] reflux, etc.)

8. Documented gastroduodenal ulcer or any GI bleeding (except hemorrhoidal) within the
last 6 months

9. Uncontrolled diabetes

10. Screening laboratory test results of serum creatinine ≥ 1.5 times upper limit of
normal; aspartate aminotransferase (AST), alanine aminotransferase (ALT), or
gamma-glutamyltransferase (GGT) ≥ 3 times upper limit of normal; and hemoglobin less
than or equal to lower limit of normal

11. Documented alcohol or drug abuse within 1 year

12. If female, breast-feeding

13. Major surgery or previous damage to the study knee at any time, or minor knee surgery
to the study knee within 1 year

14. Requires oral or intra-muscular corticosteroids, or received an intra articular
corticosteroid injection into the study knee within the past 90 days, or into any
other joint within the past 30 days, or currently applying topical corticosteroids
onto the study knee

15. Received intra-articular viscosupplementation (eg, hylan G-F 20 [Synvisc®]) in the
study knee in the past 6 months

16. On prior stable therapy (ie, more than 3 days per week for the previous month) with an
opioid analgesic prior to the screening visit will be excluded.

17. Recently started taking a sedative hypnotic medication for insomnia

18. Taking anti-depressants

19. Not willing to discontinue prohibited medications/therapies

20. Cannot tolerate acetaminophen

21. Re-entering study after dropping out or withdrawn from study

22. Used another investigational drug within the previous 30 days

23. On or currently applying for disability benefits on the basis of knee OA

24. History of fibromyalgia

25. Other painful or disabling conditions affecting the knee or leg, or disabling
condition of the hands (used to apply the study drug)

26. Skin disorder with current involvement on the hands (used to apply the study drug) or
the knee(s) (application site)

27. Referred to an orthopedic surgeon for consideration of, or been advised to have, knee
replacement or knee reconstruction surgery

28. Radiologic evidence of OA of the knee advanced to the point that all cartilage has
been eroded (ie, bone on bone)

29. Recently started using a cane within the past 30 days

30. History of chronic headaches that may require more than occasional use of rescue
medication for headaches