A Phase III, 12-week, Multicentre, Double-blind, Double-dummy, Randomised, Placebo- and Active Comparator-Controlled, Parallel Group study to investigate the Efficacy and Safety of GW406381 1mg, 5mg, 10mg, 25mg and 50mg administered orally once daily, in adults with Osteoarthritis of the knee

INTERVENTION: Product Name: GW406381 Product Code: GW406381X Pharmaceutical Form: Capsule, hard CAS Number: 221148‐46‐5 Current Sponsor code: GW406381 Other descriptive name: GW406381X Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: GW406381 Product Code: GW406381X Pharmaceutical Form: Capsule, hard CAS Number: 221148‐46‐5 Current Sponsor code: GW406381 Other descriptive name: GW406381X Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: GW406381 Product Code: GW406381X Pharmaceutical Form: Capsule, hard CAS Number: 221148‐46‐5 Current Sponsor code: GW406381 Other descriptive name: GW406381X Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: GW406381 Product Code: GW406381X Pharmaceutical Form: Capsule, hard CAS Number: 221148‐46‐5 Current Sponsor code: GW406381 Other descriptive name: GW406381X Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: GW406381 Product Code: GW406381X Pharmaceutical Form: Capsule, hard CAS Number: 221148‐46‐5 Current Sponsor code: GW406381 Other descriptive name: GW406381X Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Trade Name: Celebra Product Name: Celecoxib Pharmaceutical Form: Capsule, hard INN or Proposed INN: Celecoxib CAS Number: 169590‐42‐5 Current Sponsor code: Celecoxib Concentration unit: mg milligram(s) Conc CONDITION: Osteoarthritis of the Knee ; MedDRA version: 7.1 Level: LLT Classification code 10023476 PRIMARY OUTCOME: Main Objective: • To evaluate the clinical efficacy of GW406381 versus placebo in the treatment of the signs and symptoms of osteoarthritis of the knee Primary end point(s): • Change from baseline to week 12 in Western Ontario and McMasters Universities OA Index (WOMAC) pain subscale score; • Change from baseline to week 12 in WOMAC physical function subscale score; • Change from baseline to week 12 in the patient global assessment of arthritis condition.; Secondary Objective: • To evaluate the safety and tolerability of GW406381 administered orally to subjects with osteoarthritis of the knee; • To evaluate the optimal therapeutic dose(s) of GW406381 for further clinical investigations in osteoarthritis; • To explore the clinical efficacy of GW406381 versus celecoxib in the treatment of the signs and symptoms of osteoarthritis of the knee; • To evaluate health outcomes data generated from subject completed questionnaires; • To evaluate population pharmacokinetics (PK) of GW406381 in subjects with osteoarthritis of the knee.; INCLUSION CRITERIA: 1. Subject is male or female outpatient, = 40 years of age. A female is eligible to participate in this study if she is of: a Non‐childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre‐menarchal or post‐menopausal); or, b Child‐bearing potential has a negative pregnancy test and is not lactating at the Screening and Baseline/Randomisation Visits and agrees to satisfy one of the requirements listed in Appendix 2: Acceptable Methods of Contraception. 2. Subject is able and willing to give written informed consent 3. Subject is able to read, comprehend and record information required in the protocol e.g. complete assessments using an electronic device 4. Meets ACR clinical and radiographic criteria for classification of idiopathic (primary) osteoarthritis of the knee as defined by: knee pain and radiographic osteophytes and at least one of the following: i. Age > 50 years ii. Morning sti