A Study of Duloxetine in Patients With Osteoarthritis Knee Pain

A Phase 3b Study to Assess the Efficacy of Duloxetine 60 mg Once Daily Compared With Placebo on the Reduction of Pain Caused by Osteoarthritis of the Knee, in a 13-week, Double-blind, Randomized Study

The primary purpose of this study is to determine if duloxetine 60 mg once daily (QD) reduces pain severity in patients with osteoarthritis (OA) knee pain compared with placebo.

Inclusion Criteria:

• Male or female outpatients with osteoarthritis knee pain for greater than or equal to 14 days of each month for 3 months prior to study entry.
• Have a rating of greater than or equal to 4 on the BPI average pain item (Question 3 of the Brief Pain Inventory [BPI] modified short form) at screening and randomization

Exclusion Criteria:

• Have had any previous exposure to duloxetine.
• Have any previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder.
• Have Major Depression Disorder as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, as assessed by the Mini International Neuropsychiatric Interview (Sheehan et al. 1998), or diagnosed within the past year.
• Have a history of substance abuse or dependence within the past year, excluding nicotine and caffeine.
• Are taking any excluded medications that cannot be discontinued at screening visit.
• Have current or pending disability compensation or litigation issues that may compromise response to treatment, in the opinion of the investigator.
• Have had treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of randomization or the potential need to use an MAOI during the study or within 5 days of discontinuation of study drug.
• Have a positive urine drug screen for any substance of abuse or excluded medication.
• Are pregnant or breast-feeding.
• Have serious cardiovascular, hepatic, renal, respiratory, or hematologic illness, or other medical or psychiatric condition that, in the opinion of the investigator, would compromise participation or be likely to lead to hospitalization during the course of the study.
• Have a history of recurrent seizures other than febrile seizures.
• Are judged by the investigator to be at suicidal risk.
• Have uncontrolled narrow-angle glaucoma.
• Have acute liver injury (such as hepatitis) or severe cirrhosis (Child- Pugh Class C).
• Have known hypersensitivity to duloxetine or any of the inactive ingredients or patients with frequent or severe allergic reactions to multiple medications.
• Have frequent falls that could result in hospitalization or could compromise response to treatment.
• Have a confounding painful condition that may interfere with assessment of the index joint, that is, knee. (Knee pain should be the predominant pain. Mild OA pain of other joints is allowed.)
• Have a diagnosis of inflammatory arthritis (that is, rheumatoid arthritis) or an autoimmune disorder (excluding inactive Hashimoto's thyroiditis).
• Have received intraarticular hyaluronate or steroids, joint lavage, or other invasive therapies to the knee in the past 3 months.
• Have had knee arthroscopy of the index knee within the past year or joint replacement of the index knee at anytime.
• Have surgery planned during the study for the index joint.
• Have a body mass index (BMI) over 40.
• Use of acupuncture, chiropractic maneuvers, transcutaneous electrical nerve stimulation (TENS), or similar procedures aimed to relieve any kind of pain.
• Patients who are anticipated by the investigator to require use of analgesic agents including but not limited to non-steroidal anti-inflammatory drugs(NSAIDs), acetaminophen/paracetamol, and opioids, or other excluded medication for the duration of the study.
• Are unwilling or unable to comply with the data collection method used to record their patient rated outcome data.