<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/NCT02214888</url>
  </required_header>
  <id_info>
    <org_study_id>1175.18</org_study_id>
    <nct_id>NCT02214888</nct_id>
  </id_info>
  <brief_title>Efficacy, Safety and Pharmacokinetics of BIRB 796 BS Tablets in Patients With Active Rheumatoid Arthritis</brief_title>
  <official_title>A 12 Week Double-blind, Randomized, Placebo-controlled Trial to Investigate Efficacy, Safety and Pharmacokinetics of BIRB 796 BS Tablets at Doses of 50 and 70 mg Administered Twice a Day in Patients With Active Rheumatoid Arthritis Who Have Failed at Least One DMARD</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Study to determine the efficacy (including American College of Rheumatology (ACR) 20 response&#xD;
      rate), safety, and pharmacokinetics of BIRB 796 BS as monotherapy in patients with moderate&#xD;
      to severe rheumatoid arthritis who have failed at least one disease modifying antirheumatic&#xD;
      drug (DMARD)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>May 2003</start_date>
  <primary_completion_date type="Actual">January 2004</primary_completion_date>
  <phase>Phase 2</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>Number of responders according to the American College of Rheumatology (ACR) 20 criteria</measure>
    <time_frame>after 12 weeks of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Absolute differences to baseline in tender joint count (TJC, 68 joint count)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute differences to baseline swollen joint count (SJC, 66 joint count)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute differences to baseline in patients assessment of pain on a visual analogue scale (VAS)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute differences to baseline in patients global assessment of disease activity (PADA) on a VAS</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute differences to baseline in physicians global assessment of disease activity on a VAS</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute differences to baseline in patient's assessment of physical function measured by a standardised Health Assessment Questionnaire (HAQ)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute differences to baseline in concentration of C-reactive protein (CRP)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute differences to baseline in erythrocyte sedimentation rate (ESR)</measure>
    <time_frame>up to 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of responders to ACR 50</measure>
    <time_frame>after 12 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of responders to ACR 70</measure>
    <time_frame>after 12 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of responders to European League against Rheumatism (EULAR) response criteria</measure>
    <time_frame>after 12 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of drop-outs due to lack of efficacy, according to final assessment of investigator</measure>
    <time_frame>after 12 weeks of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse Events (AE)</measure>
    <time_frame>up to 12 weeks after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in laboratory tests</measure>
    <time_frame>up to 12 weeks after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in electrocardiogram (ECG)</measure>
    <time_frame>up to 12 weeks after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically relevant changes in vital signs</measure>
    <time_frame>up to 12 weeks after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of withdrawals due to AEs</measure>
    <time_frame>up to 12 weeks after first drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax,ss (Maximum measured concentration of the analyte in plasma at steady state)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-t,ss (area under the drug plasma concentration-time curve over a dosing interval (t) at steady state</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cpre (predose concentration of the analyte in Plasma)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin,ss (Minimum measured concentration of the analyte in plasma at steady state)</measure>
    <time_frame>up to 24 hours after last drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">170</enrollment>
  <condition>Arthritis, Rheumatoid</condition>
  <arm_group>
    <arm_group_label>BIRB 796 BS, low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BIRB 796 BS, high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIRB 796 BS, low dose</intervention_name>
    <arm_group_label>BIRB 796 BS, low dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIRB 796 BS, high dose</intervention_name>
    <arm_group_label>BIRB 796 BS, high dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>BIRB 796 BS, low dose</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female from 18 to 75 years of age&#xD;
&#xD;
          -  Diagnosis of rheumatoid arthritis (RA) established according to ACR criteria and date&#xD;
             of diagnosis &gt; 6 months&#xD;
&#xD;
          -  Patient belonging to functional class I, II, or III&#xD;
&#xD;
          -  Failure of at least one DMARD due to lack of efficacy or tolerability&#xD;
&#xD;
          -  2 out of the 3 following RA activity criteria: If this criterion is not met at visit&#xD;
             1, the whole set of RA activity criteria can be repeated at visit 2 (Repeated&#xD;
             screening)&#xD;
&#xD;
               -  documentation of ≥ 9 swollen joints in a 66 joint count&#xD;
&#xD;
               -  documentation of ≥ 9 tender joints in a 68 joint count&#xD;
&#xD;
               -  C-reactive protein (CRP) ≥ 1.5 mg/dl or erythrocyte sedimentation rate (ESR) ≥ 28&#xD;
                  mm/hr (or equivalent of ≥ 24mm/hr according to Panchenkov method)&#xD;
&#xD;
          -  Written informed consent in accordance with Good Clinical Practice (GCP) and local&#xD;
             legislation given prior to any study procedures, including washout of prohibited&#xD;
             medications&#xD;
&#xD;
          -  Only for centres participating in the pharmacokinetic (PK) substudy: Written informed&#xD;
             consent in accordance with GCP and local legislation for participation in the PK&#xD;
             substudy. Refusal to participate in the PK substudy is not an exclusion criterion for&#xD;
             participation in the trial&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inflammatory rheumatic disease other than RA&#xD;
&#xD;
          -  Treatment failure to a tumor necrosis factor (TNF)-blocking agent. Treatment failure&#xD;
             is defined as not achieving at least an ACR 20 response (e.g. in a clinical trial) or&#xD;
             - in clinical practice - having the TNF-blocking agent discontinued due to&#xD;
             ineffectiveness&#xD;
&#xD;
          -  History of vasculitis (characterised by e.g. nail bed hemorrhages or infarcts,&#xD;
             vasculitic purpura, ulcers or gangrene, multisensory neuropathy, vasculitic&#xD;
             retinopathy or scleritis of eyes). Isolated rheumatoid nodules of the skin are not a&#xD;
             criterion for exclusion&#xD;
&#xD;
          -  Serologic evidence of active hepatitis B and/or C&#xD;
&#xD;
          -  Known HIV-infection&#xD;
&#xD;
          -  History of prior tuberculosis infection or suspicion of active infection at screening&#xD;
             based on results of chest x-ray not older than 6 months&#xD;
&#xD;
          -  History of cardiovascular, renal, neurologic, psychiatric, liver, gastrointestinal,&#xD;
             immunologic or endocrine dysfunction if they are clinically significant. A clinically&#xD;
             significant disease is defined as one which in the opinion of the investigator may&#xD;
             either put the patient at risk because of participation in the study or a disease&#xD;
             which may influence the results of the study or the patient's ability to participate&#xD;
             in the study&#xD;
&#xD;
          -  Recent history of heart failure (i.e. three years or less) or myocardial infarction&#xD;
             (i.e. one year or less) or patients with any cardiac arrhythmia requiring drug therapy&#xD;
&#xD;
          -  History of malignant disease in the last 5 years or suspicion of active malignant&#xD;
             disease except successfully treated squamous or basal cell carcinoma of the skin&#xD;
&#xD;
          -  Screening ECG results outside of the reference range of clinical relevance including,&#xD;
             but not limited to QTcB &gt; 480 msec, PR interval &gt; 240 msec, QRS interval &gt; 110 msec&#xD;
             according to central ECG evaluation&#xD;
&#xD;
          -  Clinically significant abnormal baseline hematology, blood chemistry or urinalysis if&#xD;
             the abnormality defines a disease listed as an exclusion criterion or any of the&#xD;
             following specific laboratory abnormalities: If this criterion is not met at visit 1,&#xD;
             the laboratory assessments can be selectively repeated at visit 2 (Repeated screening)&#xD;
&#xD;
               -  alanine aminotransferase (ALT), aspartate aminotransferase (AST), or total&#xD;
                  bilirubin greater than upper limit of normal (ULN)&#xD;
&#xD;
               -  alkaline phosphatase, creatinine or white blood cell count greater than 1.5 x ULN&#xD;
&#xD;
          -  History of drug or alcohol abuse within the past two years or active drug or alcohol&#xD;
             abuse, present alcohol intake more than three drinks per day&#xD;
&#xD;
          -  Female of childbearing potential (not 6 months post- menopausal or surgically&#xD;
             sterilized) not using an approved form of birth control (hormonal contraceptives, oral&#xD;
             or injectable/implantable, intra-uterine device (IUD))&#xD;
&#xD;
          -  Inability to comply with the protocol&#xD;
&#xD;
          -  Previous enrolment in this trial or previous exposure to BIRB 796 BS in another trial&#xD;
&#xD;
          -  Hypersensitivity to trial drug&#xD;
&#xD;
        To be assessed at visit 3 (Baseline):&#xD;
&#xD;
          -  Pregnancy (to be excluded by serum and urine beta human chorion-gonadotropin&#xD;
             (βHCG)-test in women of childbearing potential) or breast feeding&#xD;
&#xD;
          -  Active vasculitis&#xD;
&#xD;
          -  Active infection or serious infectious diseases resulting in hospitalisation or&#xD;
             requiring systemic anti-infective therapy within the last 4 weeks&#xD;
&#xD;
          -  DMARD treatment within the last 4 weeks&#xD;
&#xD;
          -  Last dose given within the specified time period for one of the following compounds or&#xD;
             drugs:&#xD;
&#xD;
               -  Infliximab (Remicade®): 3 months&#xD;
&#xD;
               -  Adalimumab (D2E7): 3 months&#xD;
&#xD;
               -  Leflunomide: 3 months. If cholestyramine has been given for 10 days : 4 weeks&#xD;
&#xD;
               -  Investigational agent: 5- fold of the respective plasma half life or 4 weeks,&#xD;
                  whichever is longer&#xD;
&#xD;
          -  Treatment with systemic corticosteroids in a dose higher than 10 mg/day prednisone&#xD;
             equivalent&#xD;
&#xD;
          -  Change in treatment with nonsteroidal antiinflammatory drugs (NSAIDs) or systemic&#xD;
             corticosteroids within the last 4 weeks&#xD;
&#xD;
          -  Synovectomy, joint surgery, radio-/chemo synoviorthesis, adrenocorticotropic hormone&#xD;
             (ACTH) or any steroid injections (intraarticular, intravenous or intramuscular) within&#xD;
             the last 4 weeks&#xD;
&#xD;
          -  Participation in another clinical trial within the last 4 weeks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 12, 2014</study_first_submitted>
  <study_first_submitted_qc>August 12, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2014</study_first_posted>
  <last_update_submitted>August 12, 2014</last_update_submitted>
  <last_update_submitted_qc>August 12, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 13, 2014</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>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02214888
org study id: 1175.18
nct id: NCT02214888
lead sponsor: 
Study to determine the efficacy (including American College of Rheumatology (ACR) 20 response
      rate), safety, and pharmacokinetics of BIRB 796 BS as monotherapy in patients with moderate
      to severe rheumatoid arthritis who have failed at least one disease modifying antirheumatic
      drug (DMARD)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of responders according to the American College of Rheumatology (ACR) 20 criteria
time frame: after 12 weeks of treatment
measure: Absolute differences to baseline in tender joint count (TJC, 68 joint count)
time frame: up to 12 weeks
measure: Absolute differences to baseline swollen joint count (SJC, 66 joint count)
time frame: up to 12 weeks
measure: Absolute differences to baseline in patients assessment of pain on a visual analogue scale (VAS)
time frame: up to 12 weeks
measure: Absolute differences to baseline in patients global assessment of disease activity (PADA) on a VAS
time frame: up to 12 weeks
measure: Absolute differences to baseline in physicians global assessment of disease activity on a VAS
time frame: up to 12 weeks
measure: Absolute differences to baseline in patient's assessment of physical function measured by a standardised Health Assessment Questionnaire (HAQ)
time frame: up to 12 weeks
measure: Absolute differences to baseline in concentration of C-reactive protein (CRP)
time frame: up to 12 weeks
measure: Absolute differences to baseline in erythrocyte sedimentation rate (ESR)
time frame: up to 12 weeks
measure: Number of responders to ACR 50
time frame: after 12 weeks of treatment
measure: Number of responders to ACR 70
time frame: after 12 weeks of treatment
measure: Number of responders to European League against Rheumatism (EULAR) response criteria
time frame: after 12 weeks of treatment
measure: Number of drop-outs due to lack of efficacy, according to final assessment of investigator
time frame: after 12 weeks of treatment
measure: Number of patients with adverse Events (AE)
time frame: up to 12 weeks after first drug administration
measure: Number of patients with clinically relevant changes in laboratory tests
time frame: up to 12 weeks after first drug administration
measure: Number of patients with clinically relevant changes in electrocardiogram (ECG)
time frame: up to 12 weeks after first drug administration
measure: Number of patients with clinically relevant changes in vital signs
time frame: up to 12 weeks after first drug administration
measure: Number of withdrawals due to AEs
time frame: up to 12 weeks after first drug administration
measure: Cmax,ss (Maximum measured concentration of the analyte in plasma at steady state)
time frame: up to 24 hours after last drug administration
measure: AUC0-t,ss (area under the drug plasma concentration-time curve over a dosing interval (t) at steady state
time frame: up to 24 hours after last drug administration
measure: Cpre (predose concentration of the analyte in Plasma)
time frame: up to 24 hours after last drug administration
measure: Cmin,ss (Minimum measured concentration of the analyte in plasma at steady state)
time frame: up to 24 hours after last drug administration
arm group label: BIRB 796 BS, low dose
arm group type: Experimental
arm group label: BIRB 796 BS, high dose
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BIRB 796 BS, low dose
arm group label: BIRB 796 BS, low dose
intervention type: Drug
intervention name: BIRB 796 BS, high dose
arm group label: BIRB 796 BS, high dose
intervention type: Drug
intervention name: Placebo
arm group label: BIRB 796 BS, low dose
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid