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
- Conditions
- Osteoarthritis of the KneeMedDRA version: 7.1Level: LLTClassification code 10023476
- Registration Number
- EUCTR2005-000149-12-DK
- Lead Sponsor
- GlaxoSmithKline Research & Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1120
1.Subject is male or female outpatient, = 40 years of age.
A female is eligible to participate in this study if she is of:
aNon-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is pre-menarchal or post-menopausal); or,
bChild-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 < 30 minutes in duration
iii.Crepitus on active motion of the weight-bearing knee
5.A diagnosis of primary osteoarthritis of the knee for at least 3 months in symptom duration prior to screen
6.Documented anteroposterior radiographic evidence of tibio-femoral osteoarthritis within past 12 months (grade 2 or 3 according to the Kellgren & Lawrence scale)
7.American Rheumatism Association (ARA) functional class I, II or III (Appendix 3)
8.Has =80 mm for the WOMAC pain subscale question 1 score at screen
9.Has =50 mm for the WOMAC pain subscale question 1 score at baseline
10.Has a minimum worsening between screen and baseline of 15mm for the WOMAC pain subscale question 1 score
11.Has a minimum worsening between screen and baseline of 1 point for the patient global assessment of arthritis condition
12.Subject has taken NSAIDs/COX-2 inhibitors for the treatment of their knee OA for at least 5 out of 7 days in each of the 4 weeks preceding screen.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
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 [<325mg per day] for cardiovascular prophylaxis) are excluded; subjects may not discontinue low dose aspirin for the purpose of study participation
16.Use of a combination of a diuretic with either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB). Note that subjects taking only a diuretic, or only an ACE/ARB drug, are not excluded. Examples of agents covered by this criterion are listed in Appendix 4
17.Use of anticoagulants (warfarin, heparin) or anti-platelet aggregation agents (including low-dose aspirin) or a condition associated with decreased haemostasis
18.Subjects with any one of creatinine, bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method