Intervention: Ketorolac
Trial phase: Phase 3
ATC code: M01AB15 | S01BC05 | S01FB51
SMILES: O=C(c1ccccc1)c1ccc2n1CCC2C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 996
Group description: Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Eligibility criteria:
Inclusion Criteria:

A diagnosis of osteoarthritis of the index hip or knee based on American College of Rheumatology criteria with Kellgren Lawrence X ray Grade of 2 as diagnosed by the Central Reader
Currently receiving a stable dose regimen of oral NSAID (naproxen, celecoxib, diclofenac, aceclofenac, loxoprofen, ibuprofen, meloxicam, nabumetone, sulindac or ketoprofen) as described in the protocol along with a history of insufficient pain relief from, inability to tolerate or contraindication to taking acetaminophen and, tramadol or opioid treatments. Subjects must also maintain a stabilized, protocol specified NSAID dose regimen for at least the final 2 or 3 weeks of the Screening period
WOMAC Pain subscale score of at least 5 in the index knee or hip at Screening
Be willing to discontinue all non study pain medications for osteoarthritis and not use prohibited pain medications throughout the duration of the study
Female subjects of childbearing potential must agree to comply with protocol specified contraceptive requirements

Exclusion Criteria:

Subjects exceeding protocol defined BMI or body weight limits
History of other diseases specified in the protocol (eg, inflammatory joint diseases, crystalline diseases such as gout or pseudogout) that may involve the index joint and that could interfere with efficacy assessments
Radiographic evidence of protocol specified bone or joint conditions in any screening radiograph as determined by the central radiology reviewer
A history of osteonecrosis or osteoporotic fracture
History of significant trauma or surgery to a knee, hip or shoulder within the previous year
Planned surgical procedure during the duration of the study
Presence of conditions (eg, fibromyaliga, radiculopathy) associated with moderate to severe pain that may confound assessments or self evaluation of osteoarthritis pain
Signs or symptoms of carpal tunnel syndrome in the year prior to Screening
Considered unfit for surgery based upon American Society of Anesthesiologists physical classification system for surgery grading, or subjects who would not be willing to undergo joint replacement surgery if required
Contraindications to magnetic resonance imaging
History of intolerance or hypersensitivity to the oral NSAID (naproxen, celecoxib or diclofenac) the subject could be randomized to receive or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of this NSAID is contraindicated
History of intolerance or hypersensitivity to acetaminophen or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of acetaminophen is contraindicated
Use of prohibited medications without the appropriate washout period prior to Screening or Initial Pain Assessment Period
History of cancer within 5 years of Screening, except for cutaneous basal cell or squamous cell cancer resolved by excision
Subjects with signs and symptoms of clinically significant cardiac disease as described in the protocol
Diagnosis of a transient ischemic attack in the 6 months prior to Screening, diagnosis of stroke with residual deficits that would preclude completion of required study activities
History, diagnosis, or signs and symptoms of clinically significant neurological disease such as but not limited to peripheral or autonomic neuropathy
History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder
History of known alcohol, analgesic or drug abuse within 2 years of Screening
Previous exposure to exogenous NGF or to an anti-NGF antibody
History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG fusion protein
Poorly controlled hypertension as defined in the protocol or taking an antihypertensive that has not been stable for at least 1 month prior to Screening
Evidence of protocol defined orthostatic hypotension at Screening
Disqualifying score on the Survey of Autonomic Symptoms questionnaire at Screening
Screening AST, ALT, serum creatinine or HbA1c values that exceed protocol defined limits
Presence of drugs of abuse in screening urine toxicology panel
Positive hepatitis B, hepatitis C or HIV test results indicative of current infection
Participation in other investigational drug studies within protocol defined time limits
Pregnant, breastfeeding or female subjects of childbearing potential who are unwilling or unable to follow protocol required contraceptive requirements
Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the investigator, would make the subject inappropriate for entry into this study