Long-Term Analgesic Efficacy And Safety Of Tanezumab Alone Or In Combination With Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Versus NSAIDs Alone In Patients With Osteoarthritis Of The Knee Or Hip

• Osteoarthritis
• Arthritis

• Drug: NSAID
  
  IV doses of placebo (to match tanezumab) every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
• Biological: tanezumab
  
  IV tanezumab 5 mg every 8 weeks (through Week 48) and oral placebo for NSAID BID from Weeks 2 through 56
• Biological: tanezumab
  
  IV tanezumab 10 mg every 8 weeks (through Week 56) and oral placebo for NSAID BID from Weeks 2 through 56
• Biological: tanezumab
  
  IV tanezumab 5 mg every 8 weeks (through Week 48)
• Drug: NSAID
  
  Oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
• Biological: tanezumab
  
  IV tanezumab 10 mg every 8 weeks (through Week 48)

• Active Comparator: IV Placebo + NSAID
  
  Oral NSAID
  Intervention: Drug: NSAID
• Experimental: Tanezumab 5 mg
  
  IV tanezumab 5 mg every 8 weeks (through Week 48)
  Intervention: Biological: tanezumab
• Experimental: Tanezumab 10 mg
  
  IV tanezumab 10 mg every 8 weeks (through Week 48)
  Intervention: Biological: tanezumab
• Experimental: Tanezumab 5 mg + NSAID
  
  IV doses of tanezumab 5 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
  Interventions:
  

  • Biological: tanezumab
  • Drug: NSAID
• Experimental: Tanezumab 10 mg + NSAID
  
  IV doses of tanezumab 10 mg every 8 weeks (through Week 48) plus oral naproxen 500 mg BID for 56 weeks or oral celecoxib 100 mg BID for 56 weeks
  Interventions:
  

  • Biological: tanezumab
  • Drug: NSAID

• Hochberg MC, Tive LA, Abramson SB, Vignon E, Verburg KM, West CR, Smith MD, Hungerford DS. When Is Osteonecrosis Not Osteonecrosis?: Adjudication of Reported Serious Adverse Joint Events in the Tanezumab Clinical Development Program. Arthritis Rheumatol. 2016 Feb;68(2):382-91. doi: 10.1002/art.39492.
• Schnitzer TJ, Ekman EF, Spierings EL, Greenberg HS, Smith MD, Brown MT, West CR, Verburg KM. Efficacy and safety of tanezumab monotherapy or combined with non-steroidal anti-inflammatory drugs in the treatment of knee or hip osteoarthritis pain. Ann Rheum Dis. 2015 Jun;74(6):1202-11. doi: 10.1136/annrheumdis-2013-204905. Epub 2014 Mar 13.

Inclusion Criteria:

• Osteoarthritis of the knee or hip according to ACR criteria with Kellgren-Lawrence x-ray grade equal to, or greater than, 2.
• Patients must be experiencing some benefit from their current stable dose regimen of oral NSAID therapy of either naproxen 500-1000 mg/day or celecoxib 200 mg/day (either 100 mg BID or 200 mg QD) and be tolerating their NSAID regimen.
• Pain level and function levels as required by the protocol at Screening and Baseline.
• Willing to discontinue all non-study pain medications for osteoarthritis except rescue medication (acetaminophen) and not use prohibited pain medications throughout the duration of the study except as permitted per protocol.
• Willing and able to comply with lifestyle guidelines, scheduled visits, treatment plan, laboratory tests and other study procedures.

Exclusion Criteria:

• Pregnant women.
• BMI greater than 39.
• Fibromyalgia, regional pain caused by lumbar or cervical compression with radiculopathy or other moderate to sever pain that may confound assessments or self-evaluation of the pain associated with OA.
• Signs and symptoms of clinically significant cardiac disease with 6 months prior to screening.
• Diagnosis of TIA within 6 months prior to screening or diagnosis of stroke with residual deficits that would preclude completion of required study activities.
• History, diagnosis, signs or symptoms of clinically significant neurological and/or psychiatric disease/disorder.
• At Screening: uncontrolled hypertension, hemoglobin A1c greater than or equal to 10%, ALT or AST greater than or equal to 3X upper limit of normal, creatinine exceeding 1.7 mg/dL (men) or 1.5 mg/dL (women).
• Patients on warfarin or other coumadin anticoagulant therapy and/or lithium therapy within 30 days prior to screening.
• Known hypersensitivity to NSAIDs or cyclooxygenase inhibitors.