<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/NCT02247375</url>
  </required_header>
  <id_info>
    <org_study_id>543.14</org_study_id>
    <nct_id>NCT02247375</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics, Safety and Efficacy of BIIL 284 BS in Patients With Rheumatoid Arthritis (RA)</brief_title>
  <official_title>A Double-blind, Randomized, Three Parallel Group Placebo-controlled Study to Investigate Pharmacokinetics, Effect on Expression of CD11b/CD18 (Mac-1), as Well as Safety and Efficacy of Two Oral Doses of BIIL 284 BS (Dosage: 25 mg Daily, 150 mg Daily) in Patients With Rheumatoid Arthritis Over Two Weeks</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Safety, pharmacokinetics, pharmacodynamics [CD11b/CD18 (Mac-1) expression] and efficacy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2000</start_date>
  <primary_completion_date type="Actual">May 2000</primary_completion_date>
  <phase>Phase 1</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>Changes from baseline in Mac-1 expression</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentrations of BIIL 284 BS, BIIL 260 BS, BIIL 315 ZW and BIIL 304 ZW</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum concentration of the analyte in plasma (Cmax)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Trough concentration of the analyte in plasma shortly before drug administration in a steady state dosing interval (Cpre,ss)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to reach the maximum concentration of the analyte in plasma (tmax)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma (AUC)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to 4 weeks</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Global assessment of tolerability by the patient on a 4-point scale</measure>
    <time_frame>Up to 14 days after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Global assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>Up to 14 days after start of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in tender joint count (TJC)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
    <description>Bilateral assessment of twenty-eight joints by e.g., pressure, joint manipulation etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in swollen joint count (SJC)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
    <description>Twenty-eight joints were bilaterally assessed whether they are swollen or not</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in patient's current pain level assessment by visual analogue scale (VAS)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in patient's global assessment of disease activity by VAS</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global assessment of disease activity by investigator on a 5-point scale</measure>
    <time_frame>Up to 14 days after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline for patient's assessment of physical function</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
    <description>Functional disability was measured using the disability section of the Health Assessment Questionnaire (HAQ)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in erythrocyte sedimentation rate (ESR)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in C-reactive protein (CRP)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in american college of rheumatology (ACR) 20 score</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in disease activity score (DAS)</measure>
    <time_frame>Pre-dose, up to day 14 after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Global efficacy assessment by the patient on a 4-point scale</measure>
    <time_frame>Up to 14 days after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of withdrawals due to adverse events</measure>
    <time_frame>Up to 4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant findings in laboratory adverse events</measure>
    <time_frame>Up to 4 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with clinically significant findings in vital signs (blood pressure, pulse rate)</measure>
    <time_frame>Up to 4 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Arthritis, Rheumatoid</condition>
  <arm_group>
    <arm_group_label>Low dose of BIIL 284 BS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose of BIIL 284 BS</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>Low dose of BIIL 284 BS tablets</intervention_name>
    <arm_group_label>Low dose of BIIL 284 BS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>High dose of BIIL 284 BS tablets</intervention_name>
    <arm_group_label>High dose of BIIL 284 BS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female from 18 to 65 years of age&#xD;
&#xD;
          -  Patients suffering from active rheumatoid arthritis as defined by the ARA criteria&#xD;
             revised 1987&#xD;
&#xD;
             --- At least 4 of the following 7 criteria must have been present:&#xD;
&#xD;
               -  morning stiffness in and around the joints lasting at least 1 hour before maximal&#xD;
                  improvement for at least 6 weeks&#xD;
&#xD;
               -  arthritis (soft tissue thickening or fluid - not bony overgrowth alone) of at&#xD;
                  least 3 joint areas for at least 6 weeks&#xD;
&#xD;
               -  arthritis of hand joints (at least one area swollen in a wrist,&#xD;
                  metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joint) for at least 6&#xD;
                  weeks&#xD;
&#xD;
               -  symmetric arthritis (observed by a physician) with simultaneous involvement of&#xD;
                  the joints on both sides of the body for at least 6 weeks&#xD;
&#xD;
               -  rheumatoid nodules (observed by a physician) over bony prominences or extensor&#xD;
                  surfaces or in juxta-articular regions&#xD;
&#xD;
               -  serum rheumatoid factor positive&#xD;
&#xD;
               -  x-ray changes typical of rheumatoid arthritis (erosions or unequivocal bony&#xD;
                  decalcification localised in or most marked adjacent to the involved joints)&#xD;
&#xD;
          -  Patient belonging to the RA functional class I, II or III&#xD;
&#xD;
          -  Patient's written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy (to be excluded by pregnancy test) or breast feeding&#xD;
&#xD;
          -  Women of childbearing potential not using adequate contraception&#xD;
&#xD;
          -  Treatment with methotrexate in the previous month or intended use during the trial&#xD;
             period&#xD;
&#xD;
          -  Treatment with slow acting antirheumatic drugs (SAARDs)/disease-modifying&#xD;
             antirheumatic drugs (DMARDs) other than parenteral gold, D-penicillamine,&#xD;
             sulfasalazine, chloroquine / hydroxychloroquine corticosteroid during the last 2&#xD;
             months prior to study entry&#xD;
&#xD;
          -  Treatment with more than one SAARD/DMARD and/or corticosteroid during the last 2&#xD;
             months prior to study entry&#xD;
&#xD;
          -  Change in treatment with SAARDs/DMARDs during the last 2 months prior to study entry&#xD;
             or intended change during the trial duration&#xD;
&#xD;
          -  Change in treatment with corticosteroids during the last month prior to study entry or&#xD;
             intended change during the trial duration&#xD;
&#xD;
          -  Systemic treatment with corticosteroids at a dose higher than 10 mg/day or 0.2&#xD;
             mg/kg/day (prednisone equivalent), respectively (whichever is lower) during the last&#xD;
             month prior to study entry or their intended use during the trial treatment period&#xD;
&#xD;
          -  Change in treatment with non-steroidal anti-inflammatory drugs (NSAIDs) during the&#xD;
             last month prior to study entry or intended change during the trial duration&#xD;
&#xD;
          -  Treatment with EnbrelTM (etanercept) or experimental therapies during the last 3&#xD;
             months prior to study entry&#xD;
&#xD;
          -  Synovectomy and/or surgical treatment for RA in the previous month or during the trial&#xD;
&#xD;
          -  Clinical evidence of known severe cardiovascular, hepatic, renal, respiratory,&#xD;
             metabolic, haematological, immunological, gastro-intestinal, hormonal or mental&#xD;
             disorders&#xD;
&#xD;
          -  Any other rheumatological or non-rheumatological disease that could interfere with the&#xD;
             evaluation of efficacy and safety&#xD;
&#xD;
          -  Patients with active malignant disease&#xD;
&#xD;
          -  Patients with chronic or acute infections during the previous month&#xD;
&#xD;
          -  Patients with abnormal, clinically relevant laboratory values not related to RA&#xD;
&#xD;
          -  Participation in another clinical trial during this study or during the previous month&#xD;
&#xD;
          -  Previous participation in this trial (i.e. having been allocated a randomized&#xD;
             treatment number)&#xD;
&#xD;
          -  Patient unable to comply with the protocol&#xD;
&#xD;
          -  Patient with known drug abuse&#xD;
&#xD;
          -  Patient with known alcohol abuse&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>September 23, 2014</last_update_submitted>
  <last_update_submitted_qc>September 23, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 25, 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/NCT02247375
org study id: 543.14
nct id: NCT02247375
lead sponsor: 
Safety, pharmacokinetics, pharmacodynamics [CD11b/CD18 (Mac-1) expression] and efficacy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Changes from baseline in Mac-1 expression
time frame: Pre-dose, up to day 14 after start of treatment
measure: Plasma concentrations of BIIL 284 BS, BIIL 260 BS, BIIL 315 ZW and BIIL 304 ZW
time frame: Pre-dose, up to day 14 after start of treatment
measure: Maximum concentration of the analyte in plasma (Cmax)
time frame: Pre-dose, up to day 14 after start of treatment
measure: Trough concentration of the analyte in plasma shortly before drug administration in a steady state dosing interval (Cpre,ss)
time frame: Pre-dose, up to day 14 after start of treatment
measure: Time to reach the maximum concentration of the analyte in plasma (tmax)
time frame: Pre-dose, up to day 14 after start of treatment
measure: Area under the concentration-time curve of the analyte in plasma (AUC)
time frame: Pre-dose, up to day 14 after start of treatment
measure: Number of patients with adverse events
time frame: Up to 4 weeks
measure: Global assessment of tolerability by the patient on a 4-point scale
time frame: Up to 14 days after start of treatment
measure: Global assessment of tolerability by investigator on a 4-point scale
time frame: Up to 14 days after start of treatment
measure: Changes from baseline in tender joint count (TJC)
time frame: Pre-dose, up to day 14 after start of treatment
description: Bilateral assessment of twenty-eight joints by e.g., pressure, joint manipulation etc.
measure: Changes from baseline in swollen joint count (SJC)
time frame: Pre-dose, up to day 14 after start of treatment
description: Twenty-eight joints were bilaterally assessed whether they are swollen or not
measure: Changes from baseline in patient's current pain level assessment by visual analogue scale (VAS)
time frame: Pre-dose, up to day 14 after start of treatment
measure: Changes from baseline in patient's global assessment of disease activity by VAS
time frame: Pre-dose, up to day 14 after start of treatment
measure: Global assessment of disease activity by investigator on a 5-point scale
time frame: Up to 14 days after start of treatment
measure: Changes from baseline for patient's assessment of physical function
time frame: Pre-dose, up to day 14 after start of treatment
description: Functional disability was measured using the disability section of the Health Assessment Questionnaire (HAQ)
measure: Changes from baseline in erythrocyte sedimentation rate (ESR)
time frame: Pre-dose, up to day 14 after start of treatment
measure: Changes from baseline in C-reactive protein (CRP)
time frame: Pre-dose, up to day 14 after start of treatment
measure: Changes from baseline in american college of rheumatology (ACR) 20 score
time frame: Pre-dose, up to day 14 after start of treatment
measure: Changes from baseline in disease activity score (DAS)
time frame: Pre-dose, up to day 14 after start of treatment
measure: Global efficacy assessment by the patient on a 4-point scale
time frame: Up to 14 days after start of treatment
measure: Number of withdrawals due to adverse events
time frame: Up to 4 weeks
measure: Number of patients with clinically significant findings in laboratory adverse events
time frame: Up to 4 weeks
measure: Number of patients with clinically significant findings in vital signs (blood pressure, pulse rate)
time frame: Up to 4 weeks
arm group label: Low dose of BIIL 284 BS
arm group type: Experimental
arm group label: High dose of BIIL 284 BS
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Low dose of BIIL 284 BS tablets
arm group label: Low dose of BIIL 284 BS
intervention type: Drug
intervention name: High dose of BIIL 284 BS tablets
arm group label: High dose of BIIL 284 BS
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid