Treatment Study Topical NSAID, PENNSAID and Effect on Coagulation Values in Patients With Osteoarthritis Knee Pain Taking Warfarin (ATCCTCP-1)

Open-label active treatment Phase III study of PENNSAID (diclofenac sodium solution topical) to determine the effects on coagulation parameters, (PT, PTT, INR) in 2 subgroups of patients who have moderate to severe osteoarthritis (OA) pain of the knee currently on a stable dose of warfarin and are:

• equal to 55 or > and < than or equal to 74 years of age;
• or equal to 75 years of age and above

The objective of this study is to see if the use of PENNSAID (a topical NSAID) to treat your OA knee pain will not interfere with your current anticoagulant therapy or change your laboratory values from their baseline values.

Topical non-steroidal anti-inflammatory drugs (NSAIDs) present a safer potential alternative to oral therapy, with decreased systemic exposure to the active NSAID molecule for patients with osteoarthritis of the knee. Because of co-morbid conditions in addition to osteoarthritis knee pain some patients in this age range are required to be on a stable daily dose of anticoagulant therapy i.e. warfarin. The objective is to be able to use a safe and effective topical NSAID that will not interfere with the current anticoagulant therapy and provide effective treatment relief for the symptoms of osteoarthritis knee pain. This study will be monitoring the effects of active treatment of PENNSAID (a topical NSAID) on any untoward changes it may have on bleeding times i.e. (PT, PTT, INR) in the 2 defined active treatment subgroups.

• Osteoarthritis of the Knee
• Coagulopathy

Inclusion Criteria:

• Male or female adults > than or equal to 55 and < than or equal to 74 years of age or > than or equal to 75 years or above.
• Ambulatory subjects with moderate to severe OA of the knee with symptoms and knee pain for at least 3 months and pain on the majority of days in the last 30 days.
• Subjects with bilateral knee OA, the more symptomatic knee is the index knee and PENNSAID can be applied on both knees if both are affected.
• Radiographic evidence of Kellgren-Lawrence Grade 2-4 within the past 2 years.
• Currently on a stable dose of anticoagulant therapy i.e. coumadin for the past 2 months and expected to remain on current dose for the six week duration of the study.
• Currently taking oral NSAID and/or acetaminophen for OA knee pain must be taking it for at least an average of 25 days per month.
• Those currently taking oral NSAID must be willing to perform a 7 day washout to be eligible to be enrolled into the study.
• A pain score of > than 40mm on the Patient Pain VAS (100 mm scale) at screening and baseline visit.
• Able to comply with the study and give informed consent prior to performance of any study procedures.
• Able to read, write and understand English.

Exclusion Criteria:

• Unwilling to abstain from oral NSAIDs and/or other analgesic medication except for acetaminophen as rescue medication. Subjects taking low dose aspirin for cardiovascular health may remain on their stable dose throughout the study.
• Unwilling to abstain fom taking < than or equal to 1500mg of acetaminophen a day for rescue medication purposes during the 6 week course of the trial.
• Using a handicap assistive device i.e. cane, walker > than or equal to 50% of the time.
• Undergoing new physical therapy or participating in a weight loss or exercise program that has not been stable for at least 3 months prior to screening and won't remain stable during participation in study.
• History or diagnosis of an inflammatory arthritis i.e. rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis, or amyloidosis.
• Known or clinically suspected infection and human immunodeficiency virus (HIV), or hepatitis C or B viruses.
• History of abnormal laboratory results > that or equal to 2.5 x ULN indicative of any significant medical disease which in the opinion of the investigator, would preclude the subjects participation in the study.
• Any of the following abnormal laboratory results during screening:
• ALT and AST > than or equal to 2.5 x ULN
• Hemoglobin < than 11.5 g/dL (female) or < 13.2 g/dL (male)
• WBC < than 3500 cells/mm3
• Lymphocyte count < than or equal to 1000 cels/mm3
• Serum creatinine > than or equal 1.5 x ULN
• Platelet count below the central laboratory LLN
• Coagulation tests (PT, PTT, INR) above the central laboratory ULN
• Skin breakdown or rash at knee where topical PENNSAID is to be applied.
• Other serious uncontrolled non-malignant, significant, acute or chronic medical or psychiatric illness that, in judgment of investigator, could compromise subject safety, limit subject's ability to complete study and/or compromise the objectives of study.
• History of malignancy in the past 5 years with exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ.
• History of drug or alcohol dependence or abuse in the past 3 years.

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• Arthritis Treatment Center, Maryland