Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 1, Randomized, Placebo-Controlled, Two-Period, Fixed Sequence Study To Evaluate The Effect Of CP-690,550 On Measured Glomerular Filtration Rate In Patients With Active Rheumatoid Arthritis
Brief Summary: The purpose of study is to explore the effect of CP-690,550 (Tofacitinib) on measures of kidney function in patients with active rheumatoid arthritis (RA).


Options:
A: Inclusion Criteria:

* The patient has a diagnosis of Rheumatoid Arthritis based on the American College of Rheumatology (ACR) 1987 Revised Criteria.
* The patient has active disease as defined by both \>=4 tender or painful joints on motion and \>= 4 joints swollen; and either an erythrocyte sedimentation rate (ESR) \> 28 mm or a C-reactive protein (CRP) concentration \> 7 mg/dL.
* Patient had an inadequate response to at least one disease modifying antirheumatic drug (traditional or biologic) due to lack of efficacy or toxicity.
* Patient must remain on at least one background traditional disease modifying antirheumatic drug.
* No evidence of inadequately treated latent or active infection with Mycobacterium tuberculosis.

Exclusion Criteria:

* Blood dyscrasias including confirmed: Hemoglobin \<9 g/dL or Hematocrit \<30%; White blood cell count \<3.0 x 109/L; Absolute neutrophil count \<1.2 x 109/L; Platelet count \<100 x 109/L.
* History of any other rheumatic autoimmune disease other than Sjogren's syndrome.
* No malignancy or history of malignancy.
* History of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator, within the 6 months prior to the first dose of study drug.
B: Inclusion Criteria:

* The patient must meet the American College of Rheumatology (ACR) classification criteria for the diagnosis of rheumatoid arthritis by satisfying at least four of the seven criteria.
* The patient must have active disease at both Screening and predose on Day 1 of Period 1.
* Patient must have had an inadequate response to at least one disease-modifying antirheumatic drug (DMARD), non-biologic or biologic, due to ineffectiveness or intolerance.

Exclusion Criteria:

* Pregnant or lactating women
* Serious medical conditions that would make treatment with CP-690,550 potentially unsafe.
* A patient who has a history of asthma, multiple allergies or severe allergy (eg, anaphylaxis) to any substance. In particular, a history of allergy to iodine, povidone-iodine, iohexol or other iodinated contrast media.
C: Inclusion Criteria:

* Diagnosis of RA according to the revised 1987 criteria of the American Rheumatism Association (Arnett et al, 1988). The disease should have been diagnosed at least 6 months prior to screening.
* Active disease at the time of screening and pre-infusion as defined by:

  * \>=6 swollen joints
  * \>=6 tender joints and 2 of the following:

    * morning stiffness \>=45 min
    * ESR \>=28 mm/h
    * CRP \>=20 mg/L
* Men and women, \>=18 to \<=75 years of age
* Men and women of childbearing potential must be using adequate birth control measures (abstinence, oral contraceptives, IUD, barrier method with spermicide or, surgical sterilization) and should continue such precautions for 6 months after receiving the last infusion.
* Patients must have been using oral or parenteral MTX for at least 3 months with no break(s) in treatment of more than 2 weeks total during this period. Patients must have been on a stable dose of \>=12.5 mg/wk (maximum 20mg/wk) for at least 4 weeks prior to screening.
* Patients must be on a stable dose of folic acid prophylaxis for at least 4 weeks prior to screening.
* Patients using oral corticosteroids, must have been on a stable dose of \<=10 mg/day for at least 4 weeks prior to screening. If currently not using corticosteroids the patient must have not received corticosteroids for at least 4 weeks prior to screening.
* If using NSAIDs, patients should have been on a stable dose for at least 4 weeks prior to screening. If currently not using NSAIDs the patient must have been off for at least 4 weeks prior to screening.
* The screening laboratory tests must meet the following criteria:

  * Hemoglobin \>=5.3 mmol/L (\>=8.5 g/dL), providing a low hemoglobin level is not due to nutritional deficiencies or due to diseases other than chronic RA
  * WBC \>=3.5 x 10\^9/L
  * Neutrophils \>=1.5 x 10\^9/L
  * Platelets \>=100 x 10\^9/L
  * Serum transaminase \<=2 times the upper limit of normal
  * Alkaline phosphatase levels \<=2 times the upper limit of normal
  * Serum creatinine \<=150 µmol/L (\<=1.7 mg/dL)
* Patient must be able to adhere to the study visit schedule and other protocol requirements.
* Patient must be capable of giving informed consent and the consent must have been obtained prior to any study procedures including wash-out period.

Exclusion Criteria:

* Pregnant women, nursing mothers or a planned pregnancy within 1.5 years of enrollment.
* Patients who are incapacitated, largely or wholly bedridden or confined to a wheelchair, and who have little or no ability for self-care.
* Patients who have any current systemic inflammatory condition with signs and symptoms that might confound the evaluations of benefit from the Infliximab therapy, eg Lyme disease, or a rheumatic disease other than RA.
* Use of DMARDs other than MTX within 4 weeks prior to screening. (If a patient had prior exposure to leflunomide within the past 6 months, cholestyramine 8 g should be given 3 times daily for 11 days to rapidly lower the plasma level of leflunomide.)
* Use of intra-articular, i.m. or i.v. corticosteroids (including i.m. ACTH) within 4 weeks prior to screening.
* Have been previously treated with infliximab or genetic recombinant therapy with RA (e.g. etanercept, adalimumab).
* Treatment with any other therapeutic agent targeted at reducing TNF (eg, pentoxifylline or thalidomide) within the previous 3 months.
* Treatment with any investigational drug within the previous 3 months.
* Prior use of cyclophosphamide, nitrogen mustard, chlorambucil, or other alkylating agents.
* Have a history of any clinically significant adverse reaction to murine or chimeric proteins, including but not limited to allergic reactions.
* History of infected joint prosthesis within previous 5 years.
* Serious infections, such as hepatitis, pneumonia, pyelonephritis in the previous 3 months.
* Chronic infectious disease such as chronic renal infection, chronic chest infection with bronchiectasis or sinusitis.
* Have active TB. Also excluded are patients who have evidence of latent TB (positive PPD skin test or a history of latent TB) without adequate therapy for TB initiated prior to first infusion of study drug. Also excluded are patients with evidence of an old or latent TB infection without documented adequate therapy, if they will not be treated with antitubercular therapy during the trial. Patients with a current close contact with an individual with active TB will also be excluded. Additionally, patients who have completed treatment for active TB within the previous 2 years are now explicitly excluded from the trial. Patients with a household member who has a history of active pulmonary TB should have had a thorough evaluation for TB prior to study enrollment as recommended by a local infectious disease specialist or published local guidelines of TB control agencies. Also excluded are patients with opportunistic infections, including but not limited to evidence of active cytomegalovirus, active Pneumocystis carinii, aspergillosis, or atypical mycobacterial infection, etc, within the previous 6 months.
* Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic or cerebral disease.
* History of lymphoproliferative disease including lymphoma or signs suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic areas), or splenomegaly.
* Any current known malignancy or history of malignancy within the previous 5 years, except for squamous or basal cell carcinoma of the skin that have been treated with no evidence of recurrence.
* Patients with moderate or severe heart failure (NYHA class III/IV)
* Patients with pre-existing or recent onset of central nervous system demyelinating disorders
* Known recent substance abuse (drug or alcohol).
* Patients in whom multiple venipunctures are not feasible due to poor tolerability or lack of easy access.
* Have a known infection with HIV or known active hepatitis B/C infection (including associated chronic active hepatitis).
D: Inclusion Criteria:

* patients at least 18 years of age with moderate to severe active RA for at least 6 months;
* inadequate response to current anti-rheumatic therapies, including 1 or more traditional DMARDs;
* stable DMARD therapy for at least 8 weeks before entering study;
* patients of reproductive potential must be using reliable methods of contraception.

Exclusion Criteria:

* major surgery (including joint surgery) within 8 weeks before entering study, or planned surgery within 6 months after entering study;
* patients who have previously failed treatment with an anti-tumor necrosis factor agent;
* women who are pregnant or breast-feeding.

Answer: B