Safety and Efficacy of Etoricoxib 30 mg Versus Celecoxib 200 mg in Korean Participants With Osteoarthritis

A Phase III, 12-Week, Randomized, Active-Comparator-Controlled, Parallel-Group, Double Blind Study in Korea to Assess the Safety and Efficacy of Etoricoxib 30 mg Versus Celecoxib 200 mg in Patients With Osteoarthritis

The main purpose of this study is to establish that etoricoxib 30 mg is safe and not inferior to celecoxib 200 mg in the treatment of the signs and symptoms of osteoarthritis in Korean patients. Given that the efficacy of etoricoxib vs. placebo in the treatment of osteoarthritis has been established, and that prescription drugs, such as celecoxib, are available for the treatment of pain associated with osteoarthritis in Korea, it would be inappropriate to subject patients with a flare of osteoarthritic pain to the placebo treatment for 12 weeks, and thus the study is designed as an active-comparator study.

Inclusion Criteria:

• Patient is at least 40 years of age
• Clinical diagnosis of osteoarthritis of the knee for greater than 6 months based on clinical and radiographic criteria
• Female patients of childbearing potential must have a negative pregnancy test prior to study enrollment and must agree to remain abstinent, and use barrier, intramuscular, or implanted contraceptives from Visit 1 until 28 days after the last dose of study medication.
• Patient is of American Rheumatism Association (ARA) functional Class I, II, or III
• Patient is willing to limit alcohol intake to 2 or less drinks per day during study and the follow-up period
• Patient is willing to avoid unaccustomed physical activity for the duration of the study and follow-up period
• With the exception of osteoarthritis, the patient is judged to be in good general health based on medical history, physical exam, and routine laboratory tests
• Patient is able to read, understand and complete study questionnaires, including questions requiring a visual analog scale (VAS) response
• Patient provides written informed consent for the trial
• For prior non-steroidal anti-inflammatory drug (NSAID) users only, the patient has a history of positive therapeutic benefit with NSAIDs and has taken an NSAID prior to study enrollment and at a therapeutic dose level prior to study enrollment (Visit 1)
• For prior NSAID users only, the patient assessment of Pain Walking on a Flat Surface (WOMAC Section A, Question1) at Visit 1 (prestudy) is less than 80 mm (100 mm VAS)
• For prior NSAID users only, prior to randomization, and following discontinuation of NSAIDs during the washout period specified patients must satisfy the following 3 flare criteria: Minimum of 40 mm on patient reported Pain Walking on a Flat Surface (WOMAC Section A, Question 1); Increase of 15 mm on patient reported Pain Walking on a Flat Surface (WOMAC Section A, Question 1) compared to prestudy baseline recorded at Visit 1; and A worsening in Investigator Global Assessment of Disease Status of at least 1 category on a 5 category scale compared to Visit 1 recording
• For prior acetaminophen/paracetamol users only, patient has taken acetaminophen/paracetamol on a regular basis prior to study enrollment (Visit 1) and does not use NSAIDs for the treatment of osteoarthritis of the knee
• For prior acetominophen/paracetamol users only, at both Visits 1 and 2, patients must satisfy all of the following 3 criteria: Minimum of 40 mm on patient reported Pain Walking on a Flat Surface (WOMAC Section A, Question 1); Investigator Global Assessment of Disease Status as fair, poor, or very poor; and Minimum of 40 mm on Patient Global Assessment of Disease Status (100 mm

VAS)

Exclusion Criteria:

• Patient has a concurrent medical/arthritic disease that could confound or interfere with evaluation of efficacy
• Patient is legally incompetent (e.g., a minor or mentally incapacitated), or has active psychosis, or significant emotional problems at the time of the study which in the view of the investigator are sufficient to interfere with the conduct of the study
• Patient has a history of gastric or biliary surgery (including gastric bypass surgery), or small intestine surgery that causes clinical malabsorption
• Patient is allergic to, or has a history of a significant clinical or laboratory adverse experience associated with etoricoxib or celecoxib or any of their constituents
• Patient is allergic to acetaminophen/paracetamol, or has hypersensitivity (e.g., bronchoconstriction in association with nasal polyps) to aspirin or NSAIDs
• Patient has an estimated glomerular filtration rate is less than or equal to 30 ml/min
• Patient has Class II-IV congestive heart failure
• Patient has established ischemic heart disease, cerebrovascular disease, or peripheral vascular disease
• Patient has uncontrolled hypertension with an diastolic exclusionary limit of > 90 mm Hg and a systolic exclusionary limit of > 140 mm Hg
• Patient has moderate or severe hepatic insufficiency defined as Child Pugh score > 6
• Patient has a history of neoplastic disease
• Patient has a history of any illness, which in the opinion of the investigator, might confound the results of the study or pose additional risk to the patient
• Patient is, at the time of signing informed consent, a user of recreational or illicit drugs or has had a recent history (within the last 5 years) of drug or alcohol abuse or dependence
• Patients considered morbidly obese with a body mass index (BMI) ≥ 35 kg/m^2
• Patient has new use (within 2 weeks of Visit 1 and during the entire duration of the study and follow-up period) of physical medicine modalities involving the study joint, including but not limited to: physical therapy, chiropractic interventions, acupuncture, Transcutaneous Electrical Nerve Stimulator (TENS), and ultrasound
• Patient is expected to undergo surgery involving the study joint during the course of the study
• Patients taking oral contraceptives
• Patients using intra-articular steroids or hyaluronic acid injections to the study knee or other immunosuppressant medication within 3 months of Visit 1
• Patients using intravenous, intramuscular, or oral corticosteroids, intra-articular steroids or hyaluronic acid injections to any joint other than the study joint within 1 month of Visit 1
• Patients using topical or systemic analgesic medications within 3 days of Visit 1 and throughout the duration of the study
• Patients using non-study NSAID or cyclooxygenase 2 (COX-2) specific inhibitor during the study treatment period, with the exception of low-dose aspirin (≤ 325 mg/day)
• Patients receiving a Chinese traditional arthritis treatment within 1 week of Visit 1
• Patients with clinically significant abnormalities on Visit 1 clinical examination or laboratory safety tests. Serum transaminases should be ≤ 150% of the upper limit of normal
• Patients currently participating in or has participated in a study with an

investigational drug or device within 4 weeks of signing informed consent

• Patients with an active peptic ulcer or a history of inflammatory bowel disease
• Patients with a personal or family history of an inherited or acquired bleeding
• Patients that are pregnant or breast-feeding, or expecting to conceive within the projected duration of the study