Osteoarthritis of the Knee MedDRA version: 7.1 Level: LLT Classification code 10023476
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
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 stiffness =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Known history of hypersensitivity or intolerance to NSAIDs, aspirin, COX-2 inhibitors, unless subject has subsequently taken at least two separate NSAIDs/COX-2 inhibitors for at least 1 month without reaction. Intolerance of paracetamol/acetominophen. History of aspirin-sensitive asthma or nasal polyps 2. Any clinical or biological abnormality found at screen (other than those related to the disease under investigation) which, in the opinion of the investigator, is clinically significant and would preclude safe participation in this study (i.e. current malignancy, human immunodeficiency virus (HIV) infection, significant mental illness) 3. History of gastroduodenal perforations and/or obstructions 4. History of any gastric or duodenal surgery 5. Active gastrointestinal (GI) ulceration of the upper GI tract within the previous 6 months, bleeding of the upper GI tract within the previous year (including hematemesis) 6. History of lower GI bleeding (excluding haemorrhoids) within the past year 7. History of inflammatory bowel disease 8. Use of proton pump inhibitors (e.g., omeprazole, lansoprazole) at any dose for any period longer than 4 consecutive days during the month prior to study start or during the study unless the subject has a history of GI ulceration (> 6 months prior to study start) 9. Use of sucralfate or misoprostol 10. Use of potent CYP3A4 inhibitors i.e. ritonavir, ketoconazole, itraconazole, saquinavir, nelfinavir, troleandomycin, azithromycin and erythromycin. Other CYP3A4 inhibitors are permitted 11. History of coronary artery disease (angina [stable or unstable], myocardial infarction or any coronary artery surgery) 12. History of congestive heart failure or renal artery stenosis 13. History of stroke or transient ischemic attack 14. Uncontrolled (treated or untreated) hypertension at screen (sitting systolic blood pressure [SBP] >160mmHg and/or sitting diastolic blood pressure [DBP] >90mmHg) 15. Subjects taking aspirin (including low dose [ 1.5 times the upper limit of normal (ULN) at screen are excluded. Subjects with two or more of bilirubin, ALT or AST above the ULN are excluded 19. A history of clinically significant drug or alcohol abuse, as defined by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria [American Psychiatric Association, 1994] 20. Demonstrated allergic-type reactions to sulphonamides (including celecoxib or valdecoxib)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the clinical efficacy of GW406381 versus placebo in the treatment of the signs and symptoms of osteoarthritis of the knee;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. ;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. | — |
Countries
Denmark, Germany, Hungary, Sweden
Outcome results
None listed