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
- MedDRA version: 7.1Level: LLTClassification code 10039073Rheumatoid Arthritis
- Registration Number
- EUCTR2005-000158-61-DK
- Lead Sponsor
- GlaxoSmithKline Research & Development Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 2210
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 in the protocol : 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 at baseline 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
Listed below are the principal exclusion criteria with numbers corresponding to those used in the protocol. Please refer to protocol for full list of criteria.
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).
8. Use of proton pump inhibitors (e.g., omeprazole, lansoprazole) at a dose outside those specified in the label.
11. History of coronary artery disease (angina [stable or unstable], myocardial infarction or any coronary artery surgery). Note myocardial infarction includes history of clinical event or age-indeterminate event on ECG. Subjects with a screening ECG indicating a previous myocardial infarction, as reported by the central ECG reader, are excluded.
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 [SBP] >160mmHg and/or sitting diastolic blood pressure [DBP] >90mmHg).
15. Subjects taking aspirin regularly as an analgesic and are unable to washout 5x’s the half-life prior to base line are excluded; low dose [=325mg per day] for cardiovascular prophylaxis is permitted during the study.
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. Agents covered by this criteria are listed in (Appendix 6).
17. Use of anticoagulants (warfarin, heparin) or anti-platelet aggregation agents (excluding low-dose aspirin) or a condition associated with decreased haemostasis.
21. Participation in another investigational drug or device study during the 3 months prior to the Baseline/Randomisation Visit, 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, or will participate simultaneously in another clinical study.
23. Initiation or change of dose of a standard disease modifying anti-rheumatic drug (DMARD) within 12 weeks prior to baseline, e.g., penicillamine, sulfasalazine, oral or intramuscular gold salts, azathioprine, antimalarials and leflunomide (Arava).
24. Use of methotrexate at doses of >20mg/week or initiation or change to the dose of methotrexate within 8 weeks prior to baseline.
25. Use at doses outside those specified in the label of biological anticytokine directed therapeutics (e.g., anti-tumor necrosis factor [TNF]) or given at a dose interval other than the following: at least weekly, every 2 weeks, or every 4 weeks. These agents, at allowed dose intervals, may be used if stable for 6 months prior to baseline.
26. Use of B-cell targeted therapy (e.g., rituximab) if not stable for 6 months prior to Screen or at doses/schedules outside the label. Appropriate monitoring must have been performed.
27. Use of oral corticosteroids at doses greater than the equivalent of 10 mg/day of prednisolone/prednisone (average daily dose for patients on alternating doses) or initiation of treatment within 4 weeks prior to commencing study drug. Corticosteroid doses should remain stable throughout the study.
28. Intra-articular injections within 4 weeks prior to commencing study drug or during the study period (or anti
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