Inclusion Criteria:

• Present with Osteoarthritis of the knee based on: 1) Knee pain for at least 14 days per month for the last 3 months, 2) Osteophytes (bone spurs), 3) And at least 1 of the following: Over the age of 50, OR morning stiffness in knee for less than 30 minutes, OR crunching sensation as the knee bends back and forth (crepitus)
• Mean score of 4 or greater on the 24-hour average pain score from Visit 2 to Visit 3
• Completion of electronic daily diaries with at least 70% complete between Visit 2 and Visit 3.
• Taken Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) less than 15 days over the past month AND not taken NSAID at least 1 week prior to visit 3.
• Agree to maintain the same activity level throughout the study.
• Women who can become pregnant must test negative for pregnancy and agree to utilize medically acceptable/reliable birth control as determined by the investigator during the study and 1 month following the last dose of the study.
• Competent and freely able to give an informed consent.
• Ability to understanding and intelligibly communicate with the investigator.
• Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol.

Exclusion Criteria:

• Knee arthroscopy within past three months or any knee joint replacement.
• Surgery planned during the trial for the knee to be studied
• Prior synovial fluid analysis showing a white blood cell of 2000mm3 that is indicative of a diagnosis other than osteoarthritis
• Are non-ambulatory or require the use of crutches or a walker. Use of a cane in the hand opposite the index knee is acceptable.
• Body Mass Index over 40
• Confounding painful condition that may interfere with assessment of the index knee. (Knee pain should be the predominant pain. Mild osteoarthritis of the hands is allowed, for instance.)
• Diagnosis of inflammatory arthritis (rheumatoid arthritis) or an autoimmune disorder (except inactive Hashimoto's thyroiditis).
• Received intr-articular hyaluronate or steroids, joint lavage, or other invasive therapies to the knee in the past 3 months.
• Frequent falls that could result in hospitalization or could compromise response to treatment.
• Current or previous (within the past 1 year) Axis 1 diagnosis of major depressive disorder, mania, bipolar disorder, psychosis, dysthymia, generalized anxiety disorder, alcohol or eating disorders.
• Serious or unstable cardiovascular, hepatic, renal, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or other medical condition that in the opinion of investigator would compromise participation or be likely to lead to hospitalization during the course of the study.
• ALT > 2.0 times upper limit of normal at Visit 1, based on reference ranges of the central lab.
• Prior renal transplant, current renal dialysis, or serum creatinine laboratory value >1.5 times upper limit of normal based on the reference ranges of the central lab.
• Diagnosis or past history of glaucoma
• Are taking any excluded medications that cannot be discontinued at Visit 1.
• History of substance abuse or dependence within the past year, excluding nicotine and caffeine. Have a positive urine drug screen for any substance of abuse or excluded medication.
• History of recurrent seizures other than febrile seizures.
• Are judged by the investigator to be at suicidal risk.
• Acute liver injury (ex. hepatitis) or severe cirrhosis (Child-Pugh Class C).
• History of frequent and/or severe allergic reactions with multiple medications.
• Pregnant or breast-feeding.
• Are unwilling/unable to comply with the use of a data collection devices.
• Received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Investigator site personnel directly affiliated with this study, and/or their immediate families, or Lilly employees