Pharmacokinetics, Bioavailability and Safety of PENNSAID® Gel

Exclusion Criteria

• •Subjects will be ineligible for the study if they meet any of the following criteria:
• •1. Known hypersensitivity to diclofenac, aspirin \[acetylsalicylic acid (ASA)\] or any other NSAID, dimethyl sulfoxide (DMSO) or ethanol. This includes subjects exhibiting aspirin or other NSAID-induced symptoms, including bronchospasm, rhinitis, and urticaria or other NSAID-induced allergic symptoms.
• •2. Pregnant or lactating women. Women of reproductive potential (and women \<12 months after menopause) may not participate unless they have agreed to use an effective contraceptive method while on study.
• •3. Evidence of any serious active infections, severe uncontrolled cardiac, renal, hepatic, pulmonary or other systemic disease, significant medical or psychiatric illness, known seropositivity to HIV, known unexplained vision changes, history of unexplained syncope, lightheadedness, high blood pressure, chronic hepatic conditions like hepatic porphyria or clinically significant laboratory findings that would, in the investigators judgment, make the subject inappropriate for the study.
• •4. Documented (upper GI series or endoscopy) gastroduodenal ulcer or any GI bleeding (except hemorrhoidal) within the last 6 months prior to screening.
• •5. Abnormal hepatic and renal functions; hematologic changes:
• •* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)≥2.5 X ULN
• •* Gamma-glutamyl transpeptidase (GGT) ≥3X ULN
• •* Total bilirubin ≥1.5X ULN
• •* Serum creatinine ≥1.5X ULN
• •* Hemoglobin ≤LLN.
• •6. Major surgery or previous damage to the study knee(s) at any time (eg. total knee replacement, damage/reconstruction of the anterior or posterior cruciate ligaments), or minor knee surgery (eg, cartilage repair, collateral ligament repair, arthroscopic debridement) to the study knee(s) within 1 year prior to screening.
• •7. Administration of a sedative hypnotic medication for insomnia within 14 days prior to screening.
• •8. Administration of anti-depressants, within 60 days prior to screening.
• •9. Administration of another investigational drug within the previous 30 days prior to screening.
• •10. Skin disorder that affects palms of the hands or the application site of the knee(s).
• •11. History of chronic headaches.
• •12. Documented history of alcohol or drug abuse within 1 year prior to the screening visit
• •13. Subjects who have smoked or used nicotine-containing products within 6 months prior to Period 1 dosing.
• •14. Subjects treated with systemic or local diclofenac within one month of study Day 1.
• •15. Using artificial exposure, tanning beds, or self-tanning cream on knee area within 90 days of study start.
• •16. Donation or significant loss of blood (480 mL or more) within 30 days of dosing.
• •17. Previous participation in this study or participation in another clinical trial within 30 days prior screening.
• •18. Noncompliance with the study protocol.