<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01682512</url>
  </required_header>
  <id_info>
    <org_study_id>1301.1</org_study_id>
    <secondary_id>2011-002894-48</secondary_id>
    <nct_id>NCT01682512</nct_id>
  </id_info>
  <brief_title>Efficacy, Pharmacokinetics, and Safety of BI 695500 in Patients With Rheumatoid Arthritis</brief_title>
  <official_title>Efficacy, Pharmacokinetics, and Safety of BI 695500 Versus Rituximab in Patients With Moderately to Severely Active Rheumatoid Arthritis: a Randomized, Double-blind, Parallel Arm, Multiple Dose, Active Comparator Trial.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The primary objectives of this trial are (1) To show PK (Pharmacokinetic) similarity of BI&#xD;
      695500 to rituximab. (2)To establish statistical equivalence of efficacy of BI 695500 and&#xD;
      rituximab, in patients with moderately to severely active RA (Rheumatoid Arthritis), based on&#xD;
      the change in Disease Activity Score 28 (DAS28) score measured at 24 weeks compared to&#xD;
      Baseline and the American College of Rheumatology 20% (ACR20) response rate at Week 24.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    substance discontinued&#xD;
  </why_stopped>
  <start_date type="Actual">September 5, 2012</start_date>
  <completion_date type="Actual">October 12, 2016</completion_date>
  <primary_completion_date type="Actual">November 17, 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I</measure>
    <time_frame>Baseline and Week 24</time_frame>
    <description>The DAS28 score was derived using the formula: DAS28 (ESR) = 0.56*√(TJC28) + 0.28*√(SJC28) + 0.70*ln(ESR) + 0.014*(GH), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the General Health component of the DAS [score on a visual analogue scale (VAS) ranging from 0 (very well) to 100 (very poor)].&#xD;
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. Low disease activity is defined as a DAS28 score of ≤ 3.2 and DAS28 remission is defined as a DAS28 score of &lt; 2.6. A clinically important change in DAS28 score is defined as an improvement in DAS28 score of at least 1.2.&#xD;
The full analysis set (FAS) contained all randomized subjects who received at least one dose of trial medication, had at least one assessment of primary efficacy endpoint at Baseline and at post-baseline visit prior or at Week 24 visit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK (Part I Only): AUC0-tz (Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration, Determined Over Both Dosages)</measure>
    <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
    <description>Pharmacokinetic (PK) (Part I only): AUC0-tz (area under the plasma concentration versus time curve from time zero to the last measurable concentration, determined over both dosages). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. As per protocol all the following criteria had to be fulfilled for a patient to be defined as PK evaluable for the Pharmacokinetic analysis set (PKS):&#xD;
Full first and second dose given. Pre-dose concentration available prior to the second dose. Ability to estimate AUC during the infusion phases. Ability to estimate the AUC for the distribution phase after the second dose. Ability to estimate the terminal half-life (t1/2) after the second dose.&#xD;
gMean - Geometric Mean</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Determined Over Both Dosages)</measure>
    <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
    <description>PK (Part I only): AUC0-inf pred (area under the plasma concentration versus time curve from time zero to infinity, determined over both dosages, and extrapolated to infinity using predicted last observed quantifiable concentration). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours)</measure>
    <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
    <description>PK (Part I only): AUC0-336 (area under the plasma concentration versus time curve from time zero to 336 hours after the first dose). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>PK (Part I Only): Observed Cmax (Maximum Plasma Concentration, Determined After the Second Dose)</measure>
    <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
    <description>PK (Part I only): observed Cmax (observed maximum plasma concentration, determined after the second dose). Only subjects randomized in part I of this study are included.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II</measure>
    <time_frame>Week 24</time_frame>
    <description>A subject has an ACR20 response if all of the following occur:&#xD;
a &gt; 20% improvement in the swollen joint count (66 joints)&#xD;
a &gt; 20% improvement in the tender joint count (68 joints)&#xD;
a &gt; 20% improvement in at least 3 of the following assessments: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index, or Acute phase reactant (C-reactive protein).&#xD;
The percentage of subjects meeting the ACR20 response criteria at Week 24 (part-I and II) is presented for subjects randomised to receive BI 695500, Rituxan and MabThera.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK (Part I Only): AUC0-inf, Ppk (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Based on Individual Predicted Concentrations for Missing Data Derived From a Population PK Model, Determined Over Both Dosages)</measure>
    <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
    <description>PK (Part I only): AUC0-inf, ppk. Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. A modeling approach was used to impute missing values as well as impute missing concentrations after the first dose with a sampling schedule identical to the first 2 weeks after the second dose. A unit dose of 1000 mg was used in calculating the imputed values. The resulting dataset thus consisted of PK evaluable and PK non-evaluable patients with both measured as well as imputed concentration values. The prediction of these concentrations was based on a mixed effect modeling approach and included significant covariates as identified during the PK model development (including age, body surface area [BSA], body mass index [BMI], weight, gender, race, and formulation).</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">294</enrollment>
  <condition>Arthritis, Rheumatoid</condition>
  <arm_group>
    <arm_group_label>Part I BI 695500 group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BI 695500, Two infusions separated by 2 weeks, Intravenous infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part I Rituxan®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>rituximab, Two infusions separated by 2 weeks, Intravenous infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part I MabThera®</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>rituximab, Two infusions separated by 2 weeks, Intravenous infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part II BI 695500 group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BI 695500, Two infusions separated by 2 weeks, Intravenous infusion</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part II rituximab group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>rituximab, Two infusions separated by 2 weeks, Intravenous infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 695500</intervention_name>
    <arm_group_label>Part II BI 695500 group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 695500</intervention_name>
    <arm_group_label>Part I BI 695500 group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituxan®</intervention_name>
    <arm_group_label>Part I Rituxan®</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rituxan®</intervention_name>
    <arm_group_label>Part II rituximab group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MabThera®</intervention_name>
    <arm_group_label>Part I MabThera®</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Must give written informed consent and be willing to follow the protocol.&#xD;
&#xD;
          2. Male or female participants, between 18 and 80 years of age, who have a diagnosis of&#xD;
             moderately to severely active RA for at least 6 months as defined by at least six&#xD;
             swollen joints (66 joint count) and at least eight tender joints (68 joint count) at&#xD;
             Screening and Baseline (Day 1), and either an erythrocyte sedimentation rate (ESR) of&#xD;
             &gt; 28 mm/hour OR a C-reactive protein (CRP) level &gt; 1.0 mg/dL (normal: &lt; 0.4 mg/dL) at&#xD;
             Screening. Patients must have had an inadequate response or intolerance to&#xD;
             conventional DMARD therapy including at least one tumor necrosis factor (TNF)&#xD;
             inhibitor.&#xD;
&#xD;
          3. Positive for Radio Frequency and/or anti-CCP (Anti-cyclic citrullinated peptide)&#xD;
             antibodies.&#xD;
&#xD;
          4. Current treatment for RA on an outpatient basis:&#xD;
&#xD;
               1. Must be currently receiving and tolerating oral or parenteral MTX therapy at a&#xD;
                  dose of 15-25 mg per week (dose may be as low as 10 mg per week if the patient is&#xD;
                  unable to tolerate a higher dose) for at least 12 weeks immediately prior to Day&#xD;
                  1. The dose should be stable for at least 4 weeks prior to Day 1 until Week 24.&#xD;
                  After Week 24 the administration route can be changed at the investigator's&#xD;
                  discretion.&#xD;
&#xD;
               2. Patients must be willing to receive oral folic acid (at least 5 mg/week or as per&#xD;
                  local practice) or equivalent during the entire study (mandatory co-medication&#xD;
                  for MTX treatment).&#xD;
&#xD;
               3. Biologic agents and DMARDs (other than MTX) must be withdrawn at least 2 weeks&#xD;
                  prior to Day 1, except azathioprine and etanercept which must be withdrawn at&#xD;
                  least 4 weeks prior to Day 1; abatacept, adalimumab, anakinra, certolizumab,&#xD;
                  infliximab, and golimumab at least 8 weeks prior to Day 1; tocilizumab at least&#xD;
                  10 weeks prior to Day 1.&#xD;
&#xD;
               4. Leflunomide must be withdrawn at least 8 weeks prior to Day 1 or a minimum of 2&#xD;
                  weeks prior to Day 1 if after 11 days of standard cholestyramine washout.&#xD;
&#xD;
               5. If receiving current treatment with oral corticosteroids (other than&#xD;
                  intra-articular or parenteral), the dose must not exceed 10 mg/day prednisolone&#xD;
                  or equivalent. During the 4 weeks prior to Baseline (Day 1) the dose must remain&#xD;
                  stable.&#xD;
&#xD;
               6. Intra-articular and parenteral corticosteroids are not permitted within 6 weeks&#xD;
                  prior to Baseline Day 1 or throughout the trial, with the exception of IV&#xD;
                  administration of 100 mg methylprednisolone 30 to 60 minutes prior to each&#xD;
                  infusion as this is part of the trial procedures.&#xD;
&#xD;
               7. Any concomitant non-steroidal anti-inflammatory drugs (NSAIDs) must be stable for&#xD;
                  at least 2 weeks prior to Day 1.&#xD;
&#xD;
               8. Patients may be taking oral hydroxychloroquine provided that the dose is not&#xD;
                  greater than 400 mg/day or chloroquine provided that the dose is not greater than&#xD;
                  250 mg/day. These doses must have been stable for a minimum of 12 weeks prior to&#xD;
                  Day 1. The hydroxychloroquine or chloroquine treatment will need to be continued&#xD;
                  at a stable dose with the same formulation until the end of the trial.&#xD;
&#xD;
          5. For participants of reproductive potential (males and females), use of a reliable&#xD;
             means of contraception (e.g., hormonal contraceptive, patch, intrauterine device,&#xD;
             physical barrier) has to be used throughout trial participation. Females of&#xD;
             child-bearing potential must also agree to use an acceptable method of contraception&#xD;
             for 12 months following completion or discontinuation from the trial.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. ACR functional Class IV or wheelchair/bed bound.&#xD;
&#xD;
          2. Primary or secondary immunodeficiency (history of, or currently active), including&#xD;
             known history of human immunodeficiency virus infection.&#xD;
&#xD;
          3. History of positive purified protein derivative test (positive tuberculosis [TB] test)&#xD;
             without treatment for TB infection or chemoprophylaxis for TB exposure.&#xD;
&#xD;
          4. Positive HIV or TB at screening.&#xD;
&#xD;
          5. Known coronary artery disease or significant cardiac arrhythmias or severe congestive&#xD;
             heart failure (New York Heart Association classes III or IV), or interstitial lung&#xD;
             disease observed on chest X-ray.&#xD;
&#xD;
          6. History of IgE-mediated (immunoglobulin E) or non-IgE-mediated hypersensitivity or&#xD;
             known anaphylaxis to mouse proteins or a history of hypersensitivity to antibody&#xD;
             therapy.&#xD;
&#xD;
          7. History of cancer including solid tumors, hematologic malignancies, and carcinoma in&#xD;
             situ (except participants with previous resected and cured basal or squamous cell&#xD;
             carcinoma, treated cervical dysplasia, or treated in situ Grade I cervical cancer&#xD;
             within 5 years prior to the Screening Visit).&#xD;
&#xD;
          8. History of pancreatitis or current peptic ulcer disease.&#xD;
&#xD;
          9. Receipt of a live/attenuated vaccine within 12 weeks prior to the Screening Visit.&#xD;
&#xD;
         10. Any condition or treatment (including biologic therapies) that, in the opinion of the&#xD;
             investigator, may place the patient at unacceptable risk during the trial.&#xD;
&#xD;
         11. Pregnancy or breast feeding.&#xD;
&#xD;
         12. History of, or current, inflammatory joint disease other than RA (e.g., gout, reactive&#xD;
             arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease) or&#xD;
             other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory&#xD;
             bowel disease, pulmonary fibrosis, or Feltys syndrome, scleroderma, inflammatory&#xD;
             myopathy, mixed connective tissue disease, or any overlap syndrome).&#xD;
&#xD;
         13. Diagnosis of juvenile idiopathic arthritis, also known as juvenile RA, and/or RA&#xD;
             before age 16.&#xD;
&#xD;
         14. Any surgical procedure, including bone/joint surgery/synovectomy (including joint&#xD;
             fusion or replacement) within 12 weeks prior to the Screening Visit or planned within&#xD;
             24 weeks of the Screening Visit.&#xD;
&#xD;
         15. Lack of peripheral venous access.&#xD;
&#xD;
         16. Evidence of significant uncontrolled concomitant disease such as, but not limited to,&#xD;
             nervous system, renal, hepatic, endocrine, or gastrointestinal disorders which, in the&#xD;
             investigator's opinion, would preclude patient participation.&#xD;
&#xD;
         17. Known concurrent viral hepatitis or known positivity to HBe-ag, HBV DNA, HBV DNA&#xD;
             polymerase, HCVRNA, anti HCV antibodies.&#xD;
&#xD;
         18. Known active infection of any kind (excluding fungal infections of nail beds), or any&#xD;
             major episode of infection requiring hospitalization or treatment with IV&#xD;
             anti-infectives within 4 weeks of the Screening Visit or completion of oral&#xD;
             anti-infectives within 2 weeks of the Screening Visit.&#xD;
&#xD;
         19. History of deep space/tissue infection (e.g., fasciitis, abscess, osteomyelitis)&#xD;
             within 52 weeks of the Screening Visit.&#xD;
&#xD;
         20. History of serious infection or opportunistic infection in the last 2 years.&#xD;
&#xD;
         21. Any neurological (congenital or acquired), vascular or systemic disorder that might&#xD;
             affect any of the efficacy assessments, in particular, joint pain and swelling (e.g.,&#xD;
             Parkinson's disease, cerebral palsy, diabetic neuropathy).&#xD;
&#xD;
         22. Currently active alcohol or drug abuse or history of alcohol or drug abuse (as&#xD;
             determined by the investigator) within 52 weeks of the Screening Visit.&#xD;
&#xD;
         23. Treatment with IV Gamma Globulin or the Prosorba® Column within 6 months of the&#xD;
             Screening Visit.&#xD;
&#xD;
         24. Treatment with IV or intramuscular corticosteroids.&#xD;
&#xD;
         25. Previous treatment with a B cell modulating or cell depleting therapy.&#xD;
&#xD;
         26. Intolerance or contraindications to IV glucocorticoids.&#xD;
&#xD;
         27. AST (aspartate aminotransferase) or ALT (alanine aminotransferase)&gt; 3 times ULN (Upper&#xD;
             Limit of Normal)&#xD;
&#xD;
         28. Hemoglobin &lt; 8.0 g/dL.&#xD;
&#xD;
         29. Levels of IgG &lt; 5.0 g/L.&#xD;
&#xD;
         30. Absolute neutrophil count &lt; 1500/µL.&#xD;
&#xD;
         31. Platelet count &lt; 75000/µL.&#xD;
&#xD;
         32. Participation in any previous clinical trial within 12 weeks of Screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rheumatology Associates</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Achieve Clinical Research, LLC</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Arthritis &amp;amp;amp; Rheumatology Associates, P.C.</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <zip>85304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Arthritis and Rheumatology Research, PLLC</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Arthritis and Rheumatology Research, PLLC</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Arthritis and Rheumatology Research, PLLC</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85307</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Little Rock Diagnostic Clinic</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medvin Clinical Research</name>
      <address>
        <city>Covina</city>
        <state>California</state>
        <zip>91723</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TriWest Research Associates, LLC</name>
      <address>
        <city>El Cajon</city>
        <state>California</state>
        <zip>92020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Medical Research, LLC</name>
      <address>
        <city>Lakewood</city>
        <state>California</state>
        <zip>90712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Premiere Clinical Research, LLC</name>
      <address>
        <city>Lakewood</city>
        <state>California</state>
        <zip>90712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ProHealth Partners</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90808</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Diego Arthritis Medical Clinic</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arthritis Center Medical Group</name>
      <address>
        <city>Santa Maria</city>
        <state>California</state>
        <zip>93454</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westlake Medical Research</name>
      <address>
        <city>Thousand Oaks</city>
        <state>California</state>
        <zip>91360</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inland Rheumatology Clinical Trials, Inc.</name>
      <address>
        <city>Upland</city>
        <state>California</state>
        <zip>91786</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nascimento, Joao (Private Practice)</name>
      <address>
        <city>Bridgeport</city>
        <state>Connecticut</state>
        <zip>06606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Avail Clinical Research, LLC</name>
      <address>
        <city>DeLand</city>
        <state>Florida</state>
        <zip>32720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Horizon Research Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33175</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arthritis Associates, Inc.</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Family Clinical Trials, Incorporated</name>
      <address>
        <city>Pembroke Pines</city>
        <state>Florida</state>
        <zip>33026</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arthritis &amp;amp;amp; Rheumatology Associates of Palm Beach</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lovelace Scientific Resources, Incorporated</name>
      <address>
        <city>Venice</city>
        <state>Florida</state>
        <zip>34292</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coeur d'Alene Arthritis Clinical Trials</name>
      <address>
        <city>Coeur d'Alene</city>
        <state>Idaho</state>
        <zip>83814</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Arthritis Research</name>
      <address>
        <city>Idaho Falls</city>
        <state>Idaho</state>
        <zip>83404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Apex Medical Research</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>International Clinical Research</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia Medical Practice, PC</name>
      <address>
        <city>Columbia</city>
        <state>Maryland</state>
        <zip>21045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klein and Associates, M.D., P.A.</name>
      <address>
        <city>Cumberland</city>
        <state>Maryland</state>
        <zip>21502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Center for Rheumatology and Bone Research</name>
      <address>
        <city>Wheaton</city>
        <state>Maryland</state>
        <zip>20902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Pharmacology Study Group</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Michigan Rheumatology, PLLC</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arthritis Consultants, Inc</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Westroads Clinical Research</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Summit Medical Group</name>
      <address>
        <city>Clifton</city>
        <state>New Jersey</state>
        <zip>07012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlantic Coast Research</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albuquerque Center For Rheumatology</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arthritis and Osteoporosis Medical Associates, PLLC</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Box Arthritis &amp;amp;amp; Rheumatology of the Carolinas</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medication Management, LLC</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>STAT Research, Incorporated</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45417</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lynn Health Science Institute</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Altoona Center for Clinical Research, P.C.</name>
      <address>
        <city>Duncansville</city>
        <state>Pennsylvania</state>
        <zip>16635</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Office of Dr. Ramesh C. Gupta</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Inflammatory Disease</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ClinRX Research LLC</name>
      <address>
        <city>Carrollton</city>
        <state>Texas</state>
        <zip>75007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adriana Pop Moody Clinic PA</name>
      <address>
        <city>Corpus Christi</city>
        <state>Texas</state>
        <zip>78404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heartland Research Associates, LLC</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ClinRx Research LLC</name>
      <address>
        <city>McKinney</city>
        <state>Texas</state>
        <zip>75069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heartland Research Associates, LLC</name>
      <address>
        <city>Webster</city>
        <state>Texas</state>
        <zip>77598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Seattle Arthritis Clinic, PS</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98133</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tacoma Center for Arthritis Research, PS</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405-2395</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rheumatology and Pulmonary Clinic</name>
      <address>
        <city>Beckley</city>
        <state>West Virginia</state>
        <zip>25801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mountain State Clinical Research</name>
      <address>
        <city>Clarksburg</city>
        <state>West Virginia</state>
        <zip>26301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Médico CER</name>
      <address>
        <city>Buenos Aires</city>
        <zip>B1878DVB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Britanico de Buenos Aires</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1289AEB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Organización Médica de Investigación</name>
      <address>
        <city>Ciudad Autonoma Buenos Aires</city>
        <zip>C1015ABO</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APRILLUS</name>
      <address>
        <city>Ciudad Autonoma Buenos Aires</city>
        <zip>C1194AAN</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto CAICI</name>
      <address>
        <city>Rosario</city>
        <zip>S2000PBJ</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigaciones Reumatológicas</name>
      <address>
        <city>San Miguel de Tucuman</city>
        <zip>4000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Medico Privado de Reumatologia</name>
      <address>
        <city>San Miguel de Tucuman</city>
        <zip>T4000AXL</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Groeninge - Campus Vercruysselaan</name>
      <address>
        <city>Kortrijk</city>
        <zip>8500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MHAT - Kaspela, EOOD</name>
      <address>
        <city>Plovdiv</city>
        <zip>4002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MHAT-Plovdiv AD</name>
      <address>
        <city>Plovdiv</city>
        <zip>4002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MHAT Lyulin</name>
      <address>
        <city>Sofia</city>
        <zip>1336</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT, Clinic of Cardiology, Stara Zagora</name>
      <address>
        <city>Stara Zagora</city>
        <zip>6000</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aviva Medical Clinical Trials Group</name>
      <address>
        <city>Burlington</city>
        <state>Ontario</state>
        <zip>L7R 2H7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Interin</name>
      <address>
        <city>Santiago</city>
        <zip>7500010</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Medico Prosalud</name>
      <address>
        <city>Santiago</city>
        <zip>7510047</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico Pontificia Universidad Católica de Chile</name>
      <address>
        <city>Santiago</city>
        <zip>8330033</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinische Forschung Berlin-Buch GmbH, Berlin</name>
      <address>
        <city>Berlin</city>
        <zip>13125</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Carl Gustav Carus Dresden</name>
      <address>
        <city>Dresden</city>
        <zip>1307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SMO.MD GmbH, Magdeburg</name>
      <address>
        <city>Magdeburg</city>
        <zip>39112</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ZeFOR GmbH</name>
      <address>
        <city>Zerbst</city>
        <zip>39261</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Euroclinic of Athens</name>
      <address>
        <city>Athens</city>
        <zip>15121</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>&amp;quot;Attikon&amp;quot; University General Hospital of Attica</name>
      <address>
        <city>Haidari</city>
        <zip>12462</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Budai Irgalmasrendi Korhaz KHT.</name>
      <address>
        <city>Budapest</city>
        <zip>1027</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's University Hospital</name>
      <address>
        <city>Dublin</city>
        <zip>4</zip>
        <country>Ireland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Jesus</name>
      <address>
        <city>Cuauhtemoc</city>
        <zip>6090</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Saltillo</name>
      <address>
        <city>Saltillo</city>
        <zip>25000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigación del Noroeste</name>
      <address>
        <city>Tijuana</city>
        <zip>22010</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Institute</name>
      <address>
        <city>Tlanepantla</city>
        <zip>54055</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antonius Ziekenhuis</name>
      <address>
        <city>Sneek</city>
        <zip>8601 ZK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gabinet Internistyczno-Reumatologiczny Piotr Adrian Klimiuk</name>
      <address>
        <city>Bialystok</city>
        <zip>15-099</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Uniwersytecki nr 2 im.dr J. Biziela</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-168</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewodzki Szpital Zespolony w Elblagu</name>
      <address>
        <city>Elblag</city>
        <zip>82-300</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Specjalistyczny Osrodek Alergologiczno-Intern. ALL-MED</name>
      <address>
        <city>Krakow</city>
        <zip>31-023</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Linea Corporis Chirurgia Plastyczna Sp. z o. o.</name>
      <address>
        <city>Warszawa</city>
        <zip>02-653</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojewodzki Szpital Specjalistyczny we Wroclawiu</name>
      <address>
        <city>Wroclaw</city>
        <zip>52-224</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Garcia de Orta, EPE</name>
      <address>
        <city>Almada</city>
        <zip>2801-951</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Fernando Fonseca, EPE</name>
      <address>
        <city>Amadora</city>
        <zip>2720-276</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar do Baixo Vouga, E.P.E. Unidade de Aveiro</name>
      <address>
        <city>Aveiro</city>
        <zip>3814-501</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Português de Reumatologia</name>
      <address>
        <city>Lisboa</city>
        <zip>1050-034</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Hospitalar do Porto, EPE</name>
      <address>
        <city>Porto</city>
        <zip>4099-001</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Sao Teotónio</name>
      <address>
        <city>Viseu</city>
        <zip>3504-509</zip>
        <country>Portugal</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Ferran de Reumatologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital A Coruña</name>
      <address>
        <city>La Coruña</city>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Virgen Macarena</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Nuestra Señora de Valme</name>
      <address>
        <city>Sevilla</city>
        <zip>41014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI of Healthcare Kharkiv CCH #8, Kharkiv</name>
      <address>
        <city>Kharkiv</city>
        <zip>61176</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oleksandrivska Clinical Hospital</name>
      <address>
        <city>Kyiv</city>
        <zip>01601</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Scientific Center Academician M.D. Strazhesko</name>
      <address>
        <city>Kyiv</city>
        <zip>3680</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Volyn Reg. Center of Cardiovascular Path. and Thrombolysis</name>
      <address>
        <city>Lutsk</city>
        <zip>43024</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lviv Regional Clinical Hospital, Lviv</name>
      <address>
        <city>Lviv</city>
        <zip>79010</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M.V. Sklifosovskyi Poltava RCH, Poltava</name>
      <address>
        <city>Poltava</city>
        <zip>36011</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M.I. Pyrogov VRCH, Vinnytsia</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21018</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MCIC MC LLC Health Clinic, Vinnytsia</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21029</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vinnytsia M.I. Pyrogov NMU Ch of internal medicine #3</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21029</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia</name>
      <address>
        <city>Zaporizhzhia</city>
        <zip>69600</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Whipps Cross University Hospital</name>
      <address>
        <city>London</city>
        <zip>E11 1NR</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Belgium</country>
    <country>Bulgaria</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Hungary</country>
    <country>Ireland</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Portugal</country>
    <country>Spain</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Brazil</country>
    <country>Estonia</country>
    <country>France</country>
    <country>Guatemala</country>
    <country>Italy</country>
    <country>New Zealand</country>
    <country>Norway</country>
    <country>Peru</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>South Africa</country>
    <country>Sweden</country>
  </removed_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/</url>
    <description>Synopsis Link</description>
  </link>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>August 10, 2012</study_first_submitted>
  <study_first_submitted_qc>September 10, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <results_first_submitted>October 24, 2017</results_first_submitted>
  <results_first_submitted_qc>January 4, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">January 30, 2018</results_first_posted>
  <last_update_submitted>January 4, 2018</last_update_submitted>
  <last_update_submitted_qc>January 4, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Rituximab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were enrolled into this multi-center, randomized, double-blind, parallel arm, multiple dose, active comparator 2 part trial from 27 September 2017. Trial was terminated on 3 September 2015 and last subject completed 28 October 2016.</recruitment_details>
      <pre_assignment_details>509 subjects were screened for eligibility to participate in the trial. 293 subjects met all inclusion and exclusion criteria and were randomised to receive treatment. 6 subjects were included in an open-label safety run-in prior to randomisation in Part-I.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>BI 695500</title>
          <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
        </group>
        <group group_id="P2">
          <title>Rituxan®</title>
          <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
        </group>
        <group group_id="P3">
          <title>MabThera®</title>
          <description>Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="116"/>
                <participants group_id="P2" count="111"/>
                <participants group_id="P3" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Randomized in Part-I</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="65"/>
                <participants group_id="P3" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Randomized in Part-II</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="46"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="40"/>
                <participants group_id="P3" count="48"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="72"/>
                <participants group_id="P2" count="71"/>
                <participants group_id="P3" count="18"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study terminated by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="43"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Primary lack of efficacy</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Secondary lack of efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other than stated above</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety randomized analysis set (SAFR) contained all randomized subjects who received at least one dose of trial medication and subjects were classified according to treatment received.</population>
      <group_list>
        <group group_id="B1">
          <title>BI 695500</title>
          <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
        </group>
        <group group_id="B2">
          <title>Rituxan®</title>
          <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
        </group>
        <group group_id="B3">
          <title>MabThera®</title>
          <description>Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="116"/>
            <count group_id="B2" value="110"/>
            <count group_id="B3" value="65"/>
            <count group_id="B4" value="291"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.7" spread="10.46"/>
                    <measurement group_id="B2" value="54.0" spread="11.10"/>
                    <measurement group_id="B3" value="54.8" spread="12.22"/>
                    <measurement group_id="B4" value="54.5" spread="11.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="94"/>
                    <measurement group_id="B2" value="96"/>
                    <measurement group_id="B3" value="52"/>
                    <measurement group_id="B4" value="242"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I</title>
        <description>The DAS28 score was derived using the formula: DAS28 (ESR) = 0.56*√(TJC28) + 0.28*√(SJC28) + 0.70*ln(ESR) + 0.014*(GH), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the General Health component of the DAS [score on a visual analogue scale (VAS) ranging from 0 (very well) to 100 (very poor)].&#xD;
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. Low disease activity is defined as a DAS28 score of ≤ 3.2 and DAS28 remission is defined as a DAS28 score of &lt; 2.6. A clinically important change in DAS28 score is defined as an improvement in DAS28 score of at least 1.2.&#xD;
The full analysis set (FAS) contained all randomized subjects who received at least one dose of trial medication, had at least one assessment of primary efficacy endpoint at Baseline and at post-baseline visit prior or at Week 24 visit.</description>
        <time_frame>Baseline and Week 24</time_frame>
        <population>FAS. Since this endpoint was designed to establish statistical equivalence of efficacy of BI 695500 and Rituxan®, only subjects randomized to BI 695500 and Rituxan® in part-I of study are included.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 695500</title>
            <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O2">
            <title>Rituxan®</title>
            <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
        </group_list>
        <measure>
          <title>Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I</title>
          <description>The DAS28 score was derived using the formula: DAS28 (ESR) = 0.56*√(TJC28) + 0.28*√(SJC28) + 0.70*ln(ESR) + 0.014*(GH), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the General Health component of the DAS [score on a visual analogue scale (VAS) ranging from 0 (very well) to 100 (very poor)].&#xD;
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. Low disease activity is defined as a DAS28 score of ≤ 3.2 and DAS28 remission is defined as a DAS28 score of &lt; 2.6. A clinically important change in DAS28 score is defined as an improvement in DAS28 score of at least 1.2.&#xD;
The full analysis set (FAS) contained all randomized subjects who received at least one dose of trial medication, had at least one assessment of primary efficacy endpoint at Baseline and at post-baseline visit prior or at Week 24 visit.</description>
          <population>FAS. Since this endpoint was designed to establish statistical equivalence of efficacy of BI 695500 and Rituxan®, only subjects randomized to BI 695500 and Rituxan® in part-I of study are included.</population>
          <units>Unit on scale</units>
          <param>Least Squares Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.8" lower_limit="-2.08" upper_limit="-1.50"/>
                    <measurement group_id="O2" value="-1.4" lower_limit="-1.64" upper_limit="-1.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Equivalence for the change in DAS28 (ESR) was evaluated based on the two-sided 90% Confidence Interval (CI) for the treatment difference with respect to the mean change in the DAS28(ESR) score compared to baseline. Null hypothesis of non-equivalence was to be rejected if the 90% CI is fully contained within the interval of [-0.5, 0.5].</non_inferiority_desc>
            <param_type>Adjusted mean difference</param_type>
            <param_value>-0.4</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.83</ci_lower_limit>
            <ci_upper_limit>-0.03</ci_upper_limit>
            <estimate_desc>Adjusted mean difference was calculated as: BI 695500 - Rituxan®</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PK (Part I Only): AUC0-tz (Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration, Determined Over Both Dosages)</title>
        <description>Pharmacokinetic (PK) (Part I only): AUC0-tz (area under the plasma concentration versus time curve from time zero to the last measurable concentration, determined over both dosages). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. As per protocol all the following criteria had to be fulfilled for a patient to be defined as PK evaluable for the Pharmacokinetic analysis set (PKS):&#xD;
Full first and second dose given. Pre-dose concentration available prior to the second dose. Ability to estimate AUC during the infusion phases. Ability to estimate the AUC for the distribution phase after the second dose. Ability to estimate the terminal half-life (t1/2) after the second dose.&#xD;
gMean - Geometric Mean</description>
        <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
        <population>Pharmacokinetic analysis set (PKS) consisted of all randomized subjects who were PK evaluable based on protocol defined criteria.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 695500</title>
            <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O2">
            <title>Rituxan®</title>
            <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O3">
            <title>MabThera®</title>
            <description>Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
        </group_list>
        <measure>
          <title>PK (Part I Only): AUC0-tz (Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration, Determined Over Both Dosages)</title>
          <description>Pharmacokinetic (PK) (Part I only): AUC0-tz (area under the plasma concentration versus time curve from time zero to the last measurable concentration, determined over both dosages). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. As per protocol all the following criteria had to be fulfilled for a patient to be defined as PK evaluable for the Pharmacokinetic analysis set (PKS):&#xD;
Full first and second dose given. Pre-dose concentration available prior to the second dose. Ability to estimate AUC during the infusion phases. Ability to estimate the AUC for the distribution phase after the second dose. Ability to estimate the terminal half-life (t1/2) after the second dose.&#xD;
gMean - Geometric Mean</description>
          <population>Pharmacokinetic analysis set (PKS) consisted of all randomized subjects who were PK evaluable based on protocol defined criteria.</population>
          <units>Hour(h)*Microgram(ug)/Milliliter (mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="56"/>
                <count group_id="O3" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="171000" spread="41.1"/>
                    <measurement group_id="O2" value="167000" spread="40.5"/>
                    <measurement group_id="O3" value="193000" spread="37.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(o- tz) was compared between treatment groups BI 695500 and Rituxan.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>102.35</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>107.700</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>90.50</ci_lower_limit>
            <ci_upper_limit>115.76</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus Rituxan®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(o- tz) was compared between treatment groups BI 695500 and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>88.21</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>107.500</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>78.24</ci_lower_limit>
            <ci_upper_limit>99.46</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(o- tz) was compared between treatment groups Rituxan and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>86.18</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>107.449</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>76.50</ci_lower_limit>
            <ci_upper_limit>97.09</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: Rituxan® versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Determined Over Both Dosages)</title>
        <description>PK (Part I only): AUC0-inf pred (area under the plasma concentration versus time curve from time zero to infinity, determined over both dosages, and extrapolated to infinity using predicted last observed quantifiable concentration). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.</description>
        <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>BI 695500</title>
            <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O2">
            <title>Rituxan®</title>
            <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O3">
            <title>MabThera®</title>
            <description>Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
        </group_list>
        <measure>
          <title>PK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Determined Over Both Dosages)</title>
          <description>PK (Part I only): AUC0-inf pred (area under the plasma concentration versus time curve from time zero to infinity, determined over both dosages, and extrapolated to infinity using predicted last observed quantifiable concentration). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.</description>
          <population>PKS</population>
          <units>h*ug/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="56"/>
                <count group_id="O3" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="174000" spread="42.2"/>
                    <measurement group_id="O2" value="169000" spread="42.0"/>
                    <measurement group_id="O3" value="202000" spread="35.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(o-inf pred) was compared between treatment groups BI 695500 and Rituxan.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>102.46</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>107.939</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>90.26</ci_lower_limit>
            <ci_upper_limit>116.30</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus Rituxan®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(o-inf pred) was compared between treatment groups BI 695500 and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>86.00</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>107.404</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>76.38</ci_lower_limit>
            <ci_upper_limit>96.82</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(o-inf pred) was compared between treatment groups Rituxan and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>83.93</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>107.386</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>74.57</ci_lower_limit>
            <ci_upper_limit>94.47</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: Rituxan® versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours)</title>
        <description>PK (Part I only): AUC0-336 (area under the plasma concentration versus time curve from time zero to 336 hours after the first dose). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.</description>
        <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>BI 695500</title>
            <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O2">
            <title>Rituxan®</title>
            <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O3">
            <title>MabThera®</title>
            <description>Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
        </group_list>
        <measure>
          <title>PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours)</title>
          <description>PK (Part I only): AUC0-336 (area under the plasma concentration versus time curve from time zero to 336 hours after the first dose). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.</description>
          <population>PKS</population>
          <units>h*ug/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="56"/>
                <count group_id="O3" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49800" spread="40.1"/>
                    <measurement group_id="O2" value="51900" spread="28.9"/>
                    <measurement group_id="O3" value="55600" spread="30.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(0-336) was compared between treatment groups BI 695500 and Rituxan.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>95.87</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>106.608</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>86.21</ci_lower_limit>
            <ci_upper_limit>106.62</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus Rituxan®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(0-336) was compared between treatment groups BI 695500 and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>89.46</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>106.775</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>80.23</ci_lower_limit>
            <ci_upper_limit>99.74</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(0-336) was compared between treatment groups Rituxan and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>93.31</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>105.700</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>85.11</ci_lower_limit>
            <ci_upper_limit>102.29</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: Rituxan® versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>PK (Part I Only): Observed Cmax (Maximum Plasma Concentration, Determined After the Second Dose)</title>
        <description>PK (Part I only): observed Cmax (observed maximum plasma concentration, determined after the second dose). Only subjects randomized in part I of this study are included.</description>
        <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>BI 695500</title>
            <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O2">
            <title>Rituxan®</title>
            <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O3">
            <title>MabThera®</title>
            <description>Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
        </group_list>
        <measure>
          <title>PK (Part I Only): Observed Cmax (Maximum Plasma Concentration, Determined After the Second Dose)</title>
          <description>PK (Part I only): observed Cmax (observed maximum plasma concentration, determined after the second dose). Only subjects randomized in part I of this study are included.</description>
          <population>PKS</population>
          <units>microgram per milliliter (ug/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="56"/>
                <count group_id="O3" value="55"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="434" spread="31.1"/>
                    <measurement group_id="O2" value="462" spread="32.0"/>
                    <measurement group_id="O3" value="486" spread="28.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The similarity of observed Cmax was compared between treatment groups BI 695500 and Rituxan.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>93.97</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>105.995</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>85.32</ci_lower_limit>
            <ci_upper_limit>103.50</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus Rituxan®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of observed Cmax was compared between treatment groups BI 695500 and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>89.30</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>105.657</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>81.51</ci_lower_limit>
            <ci_upper_limit>97.83</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of observed Cmax was compared between treatment groups Rituxan and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>95.02</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>105.744</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>86.62</ci_lower_limit>
            <ci_upper_limit>104.25</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: Rituxan® versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II</title>
        <description>A subject has an ACR20 response if all of the following occur:&#xD;
a &gt; 20% improvement in the swollen joint count (66 joints)&#xD;
a &gt; 20% improvement in the tender joint count (68 joints)&#xD;
a &gt; 20% improvement in at least 3 of the following assessments: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index, or Acute phase reactant (C-reactive protein).&#xD;
The percentage of subjects meeting the ACR20 response criteria at Week 24 (part-I and II) is presented for subjects randomised to receive BI 695500, Rituxan and MabThera.</description>
        <time_frame>Week 24</time_frame>
        <population>FAS. Missing data have been imputed according to LOCF (last observation carried forward) and/or NRI (Non Responder Imputation).</population>
        <group_list>
          <group group_id="O1">
            <title>BI 695500</title>
            <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O2">
            <title>Rituxan®</title>
            <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O3">
            <title>MabThera®</title>
            <description>Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II</title>
          <description>A subject has an ACR20 response if all of the following occur:&#xD;
a &gt; 20% improvement in the swollen joint count (66 joints)&#xD;
a &gt; 20% improvement in the tender joint count (68 joints)&#xD;
a &gt; 20% improvement in at least 3 of the following assessments: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index, or Acute phase reactant (C-reactive protein).&#xD;
The percentage of subjects meeting the ACR20 response criteria at Week 24 (part-I and II) is presented for subjects randomised to receive BI 695500, Rituxan and MabThera.</description>
          <population>FAS. Missing data have been imputed according to LOCF (last observation carried forward) and/or NRI (Non Responder Imputation).</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="94"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="64"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.6"/>
                    <measurement group_id="O2" value="23.3"/>
                    <measurement group_id="O3" value="56.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK (Part I Only): AUC0-inf, Ppk (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Based on Individual Predicted Concentrations for Missing Data Derived From a Population PK Model, Determined Over Both Dosages)</title>
        <description>PK (Part I only): AUC0-inf, ppk. Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. A modeling approach was used to impute missing values as well as impute missing concentrations after the first dose with a sampling schedule identical to the first 2 weeks after the second dose. A unit dose of 1000 mg was used in calculating the imputed values. The resulting dataset thus consisted of PK evaluable and PK non-evaluable patients with both measured as well as imputed concentration values. The prediction of these concentrations was based on a mixed effect modeling approach and included significant covariates as identified during the PK model development (including age, body surface area [BSA], body mass index [BMI], weight, gender, race, and formulation).</description>
        <time_frame>Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.</time_frame>
        <population>Pharmacokinetic full analysis set (PKFS) included all randomized subjects with at least one valid PK concentration measurement. A valid PK concentration measurement is a value greater than lower limit of quantification as provided by Charles River.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 695500</title>
            <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O2">
            <title>Rituxan®</title>
            <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
          <group group_id="O3">
            <title>MabThera®</title>
            <description>Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
          </group>
        </group_list>
        <measure>
          <title>PK (Part I Only): AUC0-inf, Ppk (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Based on Individual Predicted Concentrations for Missing Data Derived From a Population PK Model, Determined Over Both Dosages)</title>
          <description>PK (Part I only): AUC0-inf, ppk. Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. A modeling approach was used to impute missing values as well as impute missing concentrations after the first dose with a sampling schedule identical to the first 2 weeks after the second dose. A unit dose of 1000 mg was used in calculating the imputed values. The resulting dataset thus consisted of PK evaluable and PK non-evaluable patients with both measured as well as imputed concentration values. The prediction of these concentrations was based on a mixed effect modeling approach and included significant covariates as identified during the PK model development (including age, body surface area [BSA], body mass index [BMI], weight, gender, race, and formulation).</description>
          <population>Pharmacokinetic full analysis set (PKFS) included all randomized subjects with at least one valid PK concentration measurement. A valid PK concentration measurement is a value greater than lower limit of quantification as provided by Charles River.</population>
          <units>h*ug/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="66"/>
                <count group_id="O2" value="65"/>
                <count group_id="O3" value="65"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="165000" spread="42.9"/>
                    <measurement group_id="O2" value="158000" spread="50.0"/>
                    <measurement group_id="O3" value="180000" spread="40.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(0-inf, ppk) was compared between treatment groups BI 695500 and Rituxan.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>104.49</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>108.044</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>91.92</ci_lower_limit>
            <ci_upper_limit>118.78</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus Rituxan®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(0-inf, ppk) was compared between treatment groups BI 695500 and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>91.39</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>107.253</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>81.38</ci_lower_limit>
            <ci_upper_limit>102.64</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: BI 695500 versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The similarity of AUC(0-inf, ppk) was compared between treatment groups Rituxan and MabThera.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Adjusted ratio of gMeans (%)</param_type>
            <param_value>87.47</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>107.896</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>77.12</ci_lower_limit>
            <ci_upper_limit>99.21</ci_upper_limit>
            <estimate_desc>Adjusted ratio of gMeans: Rituxan® versus MabThera®; standard error is geometric standard error</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first dose of study medication and prior to the last date of study medication plus 6 months (180 days); up to 48 weeks</time_frame>
      <desc>The safety randomized analysis set (SAFR) contained all randomized subjects who received at least one dose of trial medication and subjects were classified according to treatment received.</desc>
      <group_list>
        <group group_id="E1">
          <title>BI 695500</title>
          <description>Patients administered 1000 milligram per 100 milliliter (1000 mg per 100 mL) of BI 695500 concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
        </group>
        <group group_id="E2">
          <title>Rituxan®</title>
          <description>Patients administered 1000 mg per 100 mL of Rituxan® injection for intravenous (IV) use each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
        </group>
        <group group_id="E3">
          <title>MabThera®</title>
          <description>Patients administered 1000 mg per 100 mL of MabThera® concentrate for solution for intravenous (IV) infusion each at Day 1 and 15. Patients with response to treatment were administered additional infusions at Week 24 and 26.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Ischaemic cardiomyopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Anaphylactoid reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Abscess neck</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Gastroenteritis viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Pseudomonal sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Staphylococcal bacteraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Fibula fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Joint injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Multiple fractures</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Tibia fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc degeneration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="24" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="65"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="116"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="110"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study program was terminated and this study was discontinued on 3 September 2015. As a result no patients receiving study treatment in Part II of the study reached Week 24, and no conclusions regarding the efficacy of BI 695500 can be made.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim, Call Center</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01682512
org study id: 1301.1
secondary id: 2011-002894-48
nct id: NCT01682512
lead sponsor: 
The primary objectives of this trial are (1) To show PK (Pharmacokinetic) similarity of BI
      695500 to rituximab. (2)To establish statistical equivalence of efficacy of BI 695500 and
      rituximab, in patients with moderately to severely active RA (Rheumatoid Arthritis), based on
      the change in Disease Activity Score 28 (DAS28) score measured at 24 weeks compared to
      Baseline and the American College of Rheumatology 20% (ACR20) response rate at Week 24.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Change of Disease Activity Score 28 Erythrocyte Sedimentation Rate (DAS28 [ESR]) From Baseline to Week 24 (BI 695500 Versus Rituxan®) - Part I
time frame: Baseline and Week 24
description: The DAS28 score was derived using the formula: DAS28 (ESR) = 0.56*√(TJC28) + 0.28*√(SJC28) + 0.70*ln(ESR) + 0.014*(GH), where, TJC28 = 28 joint count for tenderness, SJC28 = 28 joint count for swelling, Ln(ESR) = natural logarithm of ESR, GH = the General Health component of the DAS [score on a visual analogue scale (VAS) ranging from 0 (very well) to 100 (very poor)].
DAS28 values range from 2.0 to 10.0 while higher values mean a higher disease activity. Low disease activity is defined as a DAS28 score of ≤ 3.2 and DAS28 remission is defined as a DAS28 score of < 2.6. A clinically important change in DAS28 score is defined as an improvement in DAS28 score of at least 1.2.
The full analysis set (FAS) contained all randomized subjects who received at least one dose of trial medication, had at least one assessment of primary efficacy endpoint at Baseline and at post-baseline visit prior or at Week 24 visit.
measure: PK (Part I Only): AUC0-tz (Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration, Determined Over Both Dosages)
time frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
description: Pharmacokinetic (PK) (Part I only): AUC0-tz (area under the plasma concentration versus time curve from time zero to the last measurable concentration, determined over both dosages). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. As per protocol all the following criteria had to be fulfilled for a patient to be defined as PK evaluable for the Pharmacokinetic analysis set (PKS):
Full first and second dose given. Pre-dose concentration available prior to the second dose. Ability to estimate AUC during the infusion phases. Ability to estimate the AUC for the distribution phase after the second dose. Ability to estimate the terminal half-life (t1/2) after the second dose.
gMean - Geometric Mean
measure: PK (Part I Only): AUC0-inf Pred (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Determined Over Both Dosages)
time frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
description: PK (Part I only): AUC0-inf pred (area under the plasma concentration versus time curve from time zero to infinity, determined over both dosages, and extrapolated to infinity using predicted last observed quantifiable concentration). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.
measure: PK (Part I Only): AUC0-336 (Area Under the Plasma Concentration Versus Time Curve From Time Zero to 336 Hours)
time frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
description: PK (Part I only): AUC0-336 (area under the plasma concentration versus time curve from time zero to 336 hours after the first dose). Time zero was the time the first dose started. Only subjects randomized in part I of this study are included.
measure: PK (Part I Only): Observed Cmax (Maximum Plasma Concentration, Determined After the Second Dose)
time frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
description: PK (Part I only): observed Cmax (observed maximum plasma concentration, determined after the second dose). Only subjects randomized in part I of this study are included.
measure: Percentage of Patients Meeting the ACR20 (American College of Rheumatology 20% Response Criteria) at Week 24 in Both Part-I and II
time frame: Week 24
description: A subject has an ACR20 response if all of the following occur:
a > 20% improvement in the swollen joint count (66 joints)
a > 20% improvement in the tender joint count (68 joints)
a > 20% improvement in at least 3 of the following assessments: patient's assessment of pain, patient's global assessment of disease activity, physician's global assessment of disease activity, patient's assessment of physical function, as measured by the Health Assessment Questionnaire - Disability Index, or Acute phase reactant (C-reactive protein).
The percentage of subjects meeting the ACR20 response criteria at Week 24 (part-I and II) is presented for subjects randomised to receive BI 695500, Rituxan and MabThera.
measure: PK (Part I Only): AUC0-inf, Ppk (Area Under the Plasma Concentration Versus Time Curve From Time Zero to Infinity, Based on Individual Predicted Concentrations for Missing Data Derived From a Population PK Model, Determined Over Both Dosages)
time frame: Blood PK samples were collected at -00:05 (hours: min) prior to first infusion and 03:55, 24:00, 335:55, 338:00, 339:55, 342:00, 344:00, 360:00, 432:00, 504:00, 672:00, 1176:00, 1512:00, 2352:00 and 2688:00 after first infusion.
description: PK (Part I only): AUC0-inf, ppk. Time zero was the time the first dose started. Only subjects randomized in part I of this study are included. A modeling approach was used to impute missing values as well as impute missing concentrations after the first dose with a sampling schedule identical to the first 2 weeks after the second dose. A unit dose of 1000 mg was used in calculating the imputed values. The resulting dataset thus consisted of PK evaluable and PK non-evaluable patients with both measured as well as imputed concentration values. The prediction of these concentrations was based on a mixed effect modeling approach and included significant covariates as identified during the PK model development (including age, body surface area [BSA], body mass index [BMI], weight, gender, race, and formulation).
arm group label: Part I BI 695500 group
arm group type: Experimental
description: BI 695500, Two infusions separated by 2 weeks, Intravenous infusion
arm group label: Part I Rituxan®
arm group type: Active Comparator
description: rituximab, Two infusions separated by 2 weeks, Intravenous infusion
arm group label: Part I MabThera®
arm group type: Active Comparator
description: rituximab, Two infusions separated by 2 weeks, Intravenous infusion
arm group label: Part II BI 695500 group
arm group type: Experimental
description: BI 695500, Two infusions separated by 2 weeks, Intravenous infusion
arm group label: Part II rituximab group
arm group type: Active Comparator
description: rituximab, Two infusions separated by 2 weeks, Intravenous infusion
intervention type: Drug
intervention name: BI 695500
arm group label: Part II BI 695500 group
intervention type: Drug
intervention name: BI 695500
arm group label: Part I BI 695500 group
intervention type: Drug
intervention name: Rituxan®
arm group label: Part I Rituxan®
intervention type: Drug
intervention name: Rituxan®
arm group label: Part II rituximab group
intervention type: Drug
intervention name: MabThera®
arm group label: Part I MabThera®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
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country: Argentina
country: Belgium
country: Bulgaria
country: Canada
country: Chile
country: Germany
country: Greece
country: Hungary
country: Ireland
country: Mexico
country: Netherlands
country: Poland
country: Portugal
country: Spain
country: Ukraine
country: United Kingdom
country: United States
country: Brazil
country: Estonia
country: France
country: Guatemala
country: Italy
country: New Zealand
country: Norway
country: Peru
country: Russian Federation
country: Serbia
country: South Africa
country: Sweden
url: http://trials.boehringer-ingelheim.com/
description: Synopsis Link
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Rituximab
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study program was terminated and this study was discontinued on 3 September 2015. As a result no patients receiving study treatment in Part II of the study reached Week 24, and no conclusions regarding the efficacy of BI 695500 can be made.
point of contact: 