A Randomized, Parallel Group, Double-Blind, Placebo Controlled Study to Evaluate theClinical Efficacy and Safety of BMS-582949 Given Orally to Subjects with RheumatoidArthritis Having an Inadequate Response to Methotrexate.Pharmacogenetics Blood Sample Amendment 01 (version 1.0, dated 19-Dec-2007);Revised Protocol 01, incorporating administrative letter 01 and amendment 03 (version 1.0, dated 12-Mar-2008)
- Conditions
- subjects with rheumatoid arthritis (RA) who are on background therapy with methotrexate (MTX)MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis
- Registration Number
- EUCTR2008-000170-20-FR
- Lead Sponsor
- Bristol Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
1) Signed Written Informed Consent
a) Subjects must be able to provide informed, written consent.
2) Target Population
a) Subjects must meet the criteria of the American Rheumatism Association (1987)
for the diagnosis of RA (Arnett et al, 1988) (Appendix 3). The disease must have
been diagnosed for = 6 months prior to screening.
b) Subjects must have been taking MTX for at least 3 months at a weekly dose of 7.5
to 30 mg, inclusive, and at a stable dose for 28 days prior to treatment (Day 1).
Use of parenteral MTX is acceptable as clinically indicated if subjects cannot
tolerate or absorb oral MTX.
c) Subjects must be MTX inadequate responders defined as currently having 6 or
more swollen joints and 8 or more tender joints at the screening visit (refer to
Inclusion number 5, disease activity)
3) Age and Sex
a) Men and women at least 18 years of age. Men and women of childbearing
potential are eligible if they are practicing effective contraceptive measures.
Because subjects are taking background therapy such as methotrexate for
treatment of RA, which has potential risks associated with its use in pregnancy,
subjects will be re-advised on the use of reliable contraceptive methods and on the
potential risks to a pregnancy.
Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study and for up to 4 weeks after
the last dose of investigational product in such a manner that the risk of pregnancy
is minimized.
4) Concomitant Medication (Anti-rheumatic Treatment)
a) MTX alone: Subjects who are treated only with methotrexate will not require
washout.
b) MTX plus DMARDs other than sulfasalazine or anti-malarials (eg
hydoxychloroquine, chloroquine): Subjects who are treated with MTX in
combination with another anti-rheumatic treatment (DMARD) will require
washout of the other DMARDs.
c) Drug stabilization requirements
i) If subjects are taking sulfasalazine and/or anti-malarials, which are allowed as
concomitant therapy in this study, they must be on a stable dose for 25 out of
28 days prior to treatment (Day 1).
ii) All DMARDs (except MTX, sulfasalazine and anti-malarials) must be
discontinued at least 28 days prior to treatment (Day 1). In the case of
leflunamide, the subject can be washed out with cholestyramine according to
manufacturers recommendations.
iii) Oral corticosteroid treatment must have been reduced to = 10 mg prednisone
or equivalent per day for at least 14 days and stabilized for at least 11 out of
14 days prior treatment (Day 1).
iv) Subjects who have had previous treatment with any
biologic/immunosuppresant therapy for RA require wash-out for a period of at
least 28 days or 5 half lives whichever is longer or a minimum of 3 months for
any biologic agent with an unknown half life, prior to treatment (Day 1).
v) Subjects requiring NSAIDs must be on a stable dose for at least 14 days prior
to Day 1 dose.
d) Prior treatment with up to two anti-TNFa inhibitors will be allowed.
5) Disease Activity
a) For subjects receiving MTX alone or MTX plus sulfasalizine and/or antimalarials:
At the screening visit, subjects must have the following disease activity:
i) 6 or more swollen joints (66 joint count) and
ii) 8 or more tender joints (68 joint count) and
iii) C-reactive protein (CRP) > ULN or erythrocyte sedimentation rate (ESR)
(Westergren Method) > 28 mm/hr (Both tests are required. Results will be
used from the screening visit to qualify for the study.)
b) For subje
1) Sex and Reproductive Status
a) WOCBP who are unwilling or unable to use an acceptable method to avoid
pregnancy for the entire study period and for up to 4 weeks after the last dose of
investigational product.
b) Women who are pregnant or breastfeeding
c) Women with a positive pregnancy test on enrollment or prior to investigational
product administration.
d) Men who are unwilling or unable to use an acceptable method of birth control
for the entire study period.
2) Medical History and Concurrent Diseases
a) Any clinically significant acute or chronic illness other than RA that is severe,
progressive or uncontrolled at the time of screening. This includes any current
signs or symptoms of severe, progressive or uncontrolled renal, hepatic,
hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic,
musculoskeletal, genitourinary, or thyroid disease.
b) Any major surgery within 4 weeks of screening or planned/scheduled surgery
requiring hospitalization during the time of the study.
c) Blood transfusion within 4 weeks of screening.
d) Donation of blood or plasma to a blood bank or in a clinical study within 4 weeks of screening.
e) Any condition that could impact upon the absorption of study drug. (ie, gastric
ulcer requiring therapy, gastric stapling, duodenal surgery, malabsorption syndrome).
f) Subjects (currently or within 3 months) requiring chronic or intermittent medical
therapy or surgical intervention for gastrointestinal disease including
gastrointestinal ulceration, chronic heartburn, esophageal reflux, gastric or
duodenal ulcer and/or gastritis.
g) Any infection requiring systemic anti-microbial treatment that completed within 4
weeks of enrollment.
h) Major infection requiring hospitalization or receipt of intravenous antibiotics
within 2 months prior to enrollment.
i) Subjects at risk for tuberculosis (TB).
j) Have a history of opportunistic infection and/or evidence of active infection
including but not limited to HIV, Hepatitis B or C viruses.
k) History of lymphoproliferative disease, including lymphoma, or signs suggestive
of possible lymphoproliferative disease, such as lymphadenopathy of unusual
size, location, or clinically significant splenomegaly.
l) Any known malignancy or history of malignancy within 5 years including
carcinoma in situ prior to enrollment, with the exception of basal cell or
squamous cell carcinoma of the skin that has been excised with no evidence of
recurrence (squamous cell carcinoma of other location is exclusionary).
m) Subjects who have received treatment with any investigational drug within the
previous 30 days or 5 half-lives of the Day 1 dose, whichever is greater.
n) Subjects who have received a live vaccine within 3 months of Day 1 dosing.
3) Physical and Laboratory Test Findings
a) Subjects at screening with PT and/or aPTT and/or INR values = 1.05 X ULN.
b) Subjects at screening with ALT or AST elevations = 1.5 X ULN or with a history
of frequent or recent ALT or AST elevations are excluded.
c) Subjects at screening with CK elevations = 2 X ULN or with a history of frequent
or recent CK elevations are excluded.
d) Any clinically significant (as determined by the investigator) vital signs and/or physical examination finding.
e) Positive blood screen for hepatitis B surface Ag and hepatitis C antibody.
f) Chest radiograph at screening showing evidence of chronic infection, malignancy
or inflammation.
g) Screening ECG showing clinically significant abnormalities.
4) Proh
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