A Study Comparing Duloxetine Versus Placebo in Patients Taking a Nonsteroidal Anti-inflammatory Drug (NSAID) for Knee Pain Due to Osteoarthritis

A Randomized, Placebo-Controlled Trial of Duloxetine Added to Nonsteroidal Anti-inflammatory Drugs in Patients With Knee Pain Due to Osteoarthritis Who Have Had Suboptimal Response to Nonsteroidal Anti-inflammatory Drug Treatment.

The study will test the hypothesis that, in patients with knee pain due to osteoarthritis (OA) who are taking nonsteroidal anti-inflammatory drugs (NSAIDs) but still have significant knee pain, duloxetine 60 to 120 milligrams (mg) daily for 10 weeks will provide additional reduction in pain.

Duloxetine has been studied in pain due to osteoarthritis (OA) in 2 previous placebo controlled clinical trials. In clinical practice, when nonsteroidal anti-inflammatory drugs (NSAIDs) are ineffective in reducing pain due to OA, clinicians often add a second agent without discontinuing NSAIDs. In this study, we will investigate whether adding duloxetine to NSAIDs provides additional pain relief and functional improvement in patients with knee pain due to OA.

Inclusion Criteria:

• Present with knee pain due to osteoarthritis (OA) based on OA clinical and radiographic diagnostic criteria.
• Knee Pain for > 14 days of each month for the 3 months directly preceding study entry.
• Taking nonsteroidal anti-inflammatory drugs (NSAIDs) for knee pain due to OA on most days in the 3 months immediately preceding study entry.

Exclusion Criteria:

• History of intolerance or nonresponsiveness to an adequate trial of duloxetine used for any indication, in the opinion of the investigator.
• Previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder.
• Have major depressive disorder (MDD) as determined using depression module of the Mini International Neuropsychiatric Interview (MINI).
• Judged clinically by the investigator to be at suicidal risk by examination or using the Columbia Suicide Severity Rating Scale (C-SSRS).
• History of substance abuse or dependence within the past year, excluding nicotine and caffeine.
• Positive urine drug screen for any substance of abuse or excluded medication.
• Opioid dependent in the opinion of the investigator, taking opioids more than 3 days a week, or unwilling to discontinue opioids during the study period.
• Known hypersensitivity to duloxetine or its inactive ingredients.
• History of intolerance or hypersensitivity to NSAIDS, Cyclooxygenase (COX-2) inhibitors, or proton pump inhibitors.
• History of peptic ulcer disease, bleeding disorder, gastrointestinal bleeding, or any abnormal bleeding.
• Baseline hemoglobin measurement of <11 grams per deciliter (g/dL) for males, or <10 g/dL for females.
• Serious or unstable cardiovascular, hepatic, renal, metabolic, respiratory, or hematologic illness, symptomatic peripheral vascular disease, or any other medical or psychiatric condition that would compromise participation or be likely to lead to hospitalization or a change in medication during the course of the study.
• Uncorrected thyroid disease, uncontrolled narrow-angle glaucoma, uncontrolled or poorly controlled hypertension, or history of seizures.
• Active liver injury (such as hepatitis) or any degree of hepatic insufficiency (Child-Pugh Class C).
• Frequent falls that could result in hospitalization or could compromise response to treatment.
• Confounding painful condition that may interfere with assessment of the index knee.
• Chronic widespread pain affecting all four quadrants of the body, or diagnosis of fibromyalgia.
• Received intra-articular hyaluronate (Synvisc), steroids, joint lavage, or other invasive therapies to the knee in the past 6 months.
• Arthroscopy of the index knee within the past year or joint replacement of the index knee at anytime.
• Diagnosis of inflammatory arthritis (that is, rheumatoid arthritis, psoriatic arthritis, reactive arthritis, ankylosing spondylitis, etc.) or an autoimmune disorder (excluding inactive Hashimoto's thyroiditis).
• Prior synovial fluid analysis showing a white blood cell count greater than or equal to 2000 cubic millimeters (mm^3) that is indicative of a diagnosis other than OA, or have a history of gout or pseudogout.
• Radiographic evidence of end-stage (bone on bone) OA in either knee.
• Knee replacement surgery planned within the next 6 months.
• Nonambulatory or requiring the use of crutches, a walker, or more than 1 cane.
• Body mass index (BMI) >40.