A Phase III, 12-Week, Multicentre, Double-Blind, Randomised, Placebo- and Active Comparator-Controlled, Parallel Group Study to Investigate the Efficacy and Safety of GW406381, 5mg, 10mg, 25mg, and 50mg administered orally once daily, in Adults with Rheumatoid Arthritis

• Conditions: Rheumatoid Arthritis; MedDRA version: 7.1Level: LLTClassification code 10039073

• Registration Number: EUCTR2005-000158-61-DE
• Lead Sponsor: GlaxoSmithKline Research & Development Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-05-16
• Last Update Posted: 9 October 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 2210

Inclusion Criteria

1.Subject is a male or female outpatient, at least 18 years of age.
A female is eligible to enter and participate in the 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.Childbearing potential, has a negative pregnancy test and is not lactating at the Screening Visit and Baseline Visit, and agrees to satisfying one of the requirements listed Appendix 3: 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.Onset of RA at >16 years of age and symptom duration for >12 months.
5.Diagnosis of RA as defined by the American Rheumatism Association (ARA) 1987 criteria..
6.ARA Functional Class I, II or III.
7.Required a NSAID or COX-2 inhibitor for the treatment of their RA for at least 5 out of 7 days of each week for the 4 weeks prior to screen.
8.Satisfies all the following definitions of active disease and baseline criteria defined by:
•a minimum of six tender/painful joints with an increase of at least two tender/painful joints (or 20% increase, whichever is greater) at baseline compared to screen,plus
•a minimum of three swollen joints at baseline with an increase of at least two swollen joints (or 20% increase, whichever is greater) at baseline compared to screen,plus
•a patient’s assessment of pain (VAS) of at least 40mm at baseline with an increase of at least 10mm (or 20% increase, whichever is greater) at baseline as compared to 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

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 one 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.
3.History of gastroduodenal perforations and/or obstructions.
4.History of any gastric or duodenal surgery.
5.Active gastrointestinal 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 hemorrhoids) within the past year.
7.History of inflammatory bowel disease.
8.Use of proton pump inhibitors 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 and 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 hypertension (treated or untreated) at screen (sitting systolic blood pressure >160mmHg and/or sitting diastolic blood pressure >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.
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 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.
20.Demonstrated allergic-type reactions to sulphonamides (including celecoxib or valdecoxib).
21.Participation in another investigational drug or device study during the 3 months prior to the Baseline/Randomisation Visit or participation in a study of a marketed NSAID or COX-2 inhibitor, given in accordance with the dosage and administration section of the approved product labelling, during the month prior to the Baseline/Randomisation Visit.
22.Previous participation in an investigational study of GW406381.
23.Initiation or change of dose of a standard disease modifying anti-rheumatic drug (DMARD) within 12 weeks prior to baseline, e.g., penicillami

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified