<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/NCT02240706</url>
  </required_header>
  <id_info>
    <org_study_id>1315.7</org_study_id>
    <secondary_id>2018-002177-21</secondary_id>
    <nct_id>NCT02240706</nct_id>
  </id_info>
  <brief_title>Phase I/II Trial to Investigate BI 836858 in Myelodysplastic Syndromes</brief_title>
  <official_title>A Phase I/II, Multicentre, Open-label, Dose Escalation and Randomized Trial of BI 836858 in Patients With Low or Intermediate-1 Risk Myelodysplastic Syndromes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Phase I: To investigate maximum tolerated dose (MTD), safety and tolerability,&#xD;
      pharmacokinetics, exploratory biomarker and efficacy of BI 836858 monotherapy in patients&#xD;
      with low or intermediate-1 risk myelodysplastic syndromes (MDS) with symptomatic anemia.&#xD;
      Phase II: To investigate safety and efficacy of BI 836858 plus Best Supportive Care compared&#xD;
      to Best Supportive Care alone in low or intermediate-1 risk MDS patients with symptomatic&#xD;
      anemia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">January 22, 2015</start_date>
  <completion_date type="Actual">November 18, 2019</completion_date>
  <primary_completion_date type="Actual">November 18, 2019</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD) (Phase I)</measure>
    <time_frame>From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days</time_frame>
    <description>The MTD is defined as the highest dose of BI 836858 with less than 25% risk of the true dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period. MTD determination will be based on a Bayesian logistic regression model with overdose control.&#xD;
For any dose-escalation cohort, at least 3 patients (pts) will be required. However, in the case that only 2 pts are evaluable and neither has experienced a DLT within the first cycle (2 administrations - 28 days), then dose-escalation can occur based on these 2 pts. After all pts in a cohort have either experienced a DLT or have been observed for at least one cycle (2 administrations - 28 days) without experiencing a DLT, the Bayesian model will be updated with the newly accumulated data.&#xD;
The MTD may be considered reached if either the posterior probability of the true DLT rate in the target interval (16%-33%) is above 50%, or at least 12 pts have been treated at MTD, including the two expansion cohorts.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Patients With Dose Limiting Toxicity (DLT) (Phase I)</measure>
    <time_frame>From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days</time_frame>
    <description>Dose Limiting Toxicity (DLT):&#xD;
Grade (G) ≥ 3 (CTCAE 4.0), non disease-related, non-hematologic adverse events (AE), except:&#xD;
Laboratory abnormality, not significant by investigator or resolves spontaneously or can be recovered with appropriate treatment (T) within 5 d&#xD;
Neutrophils (NP) &lt;500 /microliters (μL) at T start, febrile neutropenia with NP &lt;500 /μL or infection with NP &lt;500 /μL will not constitute a DLT if they can be recovered with appropriate T within 14 d&#xD;
Inability to deliver study drug full dose according to the assigned dose level within cycle 1 due to drug-related AEs&#xD;
Absence of hematological recovery as following:&#xD;
NPs: G 4 (if G 0/1 at baseline (BL)) OR &lt;100 /μL and decrease of &gt;75% from BL (if G ≥2 at BL) for &gt;7 d&#xD;
Platelets: G 4 (if G 0/1 at BL) OR &lt; 10000/μL for &gt;7 d and decrease of &gt;75% from BL (if G ≥2 at BL)&#xD;
T delay of ≥4 weeks of start of Cycle 2 --If Cycle 2 is not started until 57th d as a result of drug related AE, it is considered as DLT</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase II)</measure>
    <time_frame>From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days)</time_frame>
    <description>Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator.&#xD;
A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent.&#xD;
A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase I)</measure>
    <time_frame>From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days)</time_frame>
    <description>Number of patients with red blood cell (RBC) Transfusion Independency is presented.&#xD;
Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator.&#xD;
A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent.&#xD;
A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Hematologic Improvement Neutrophils (HI-N) (Phase I)</measure>
    <time_frame>From first administration of BI 836858 until HI-N, up to 168 days (6 cycles, each of 28 days)</time_frame>
    <description>Number of patients with hematologic improvement neutrophils (HI-N) is presented.&#xD;
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:&#xD;
Neutrophil response (HI-N) - Patients with a pretreatment neutrophil count &lt;1 x 10^9/liters (L) demonstrate a neutrophil response if they have an at least 100 percent increase and an absolute increase &gt;0.5 x 10^9/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Hematologic Improvement Platelets (HI-P) (Phase I)</measure>
    <time_frame>From first administration of BI 836858 until HI-P, up to 168 days (6 cycles, each of 28 days)</time_frame>
    <description>Number of patients with hematologic improvement platelets (HI-P) is presented.&#xD;
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:&#xD;
Platelet response (HI-P) - Patients with a pretreatment platelet count &lt;100 x 109/Liters (L) demonstrate a platelet response if there is an absolute platelet increase of ≥30 x 109/L for patients starting with &gt;20 x 109/L platelets. For those with an increase from 10 x 109/L to &gt;20 x 109/L must have an increase of at least 100 percent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Hematologic Improvement Erythroid (HI-E) (Phase I)</measure>
    <time_frame>From first administration of BI 836858 until HI-E, up to 168 days (6 cycles, each of 28 days)</time_frame>
    <description>Number of patients with hematologic improvement erythroid (HI-E) is presented.&#xD;
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:&#xD;
Erythroid response (HI-E): Patients with a pretreatment hemoglobin &lt;11 grams per deciliters (g/dL) demonstrate erythroid response if their hemoglobin increases by ≥1.5 g/dL for at least eight weeks, and there is a reduction in the units of red cell transfusions by an absolute number of at least four red cell transfusions per eight weeks compared with the pretreatment transfusion number in the previous eight weeks. Only red cell transfusions given for a hemoglobin ≤9 g/dL pretreatment will count in the red cell transfusion response evaluation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to HI-E Response (Phase I)</measure>
    <time_frame>From first administration of BI 836858 until HI-E response, up to 168 days (6 cycles, each of 28 days)</time_frame>
    <description>Time to HI-E response is defined only for patients who achieve a HI-E response as follows: Time to HI-E response [days] = date of first assessment indicating HI-E response - date of first administration of trial medication + 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Mean Hemoglobin Increase ≥ 1.5 g/dL (Phase I)</measure>
    <time_frame>Up to 48 weeks</time_frame>
    <description>Number of patients with mean hemoglobin increase ≥ 1.5 grams per deciliters (g/dL) is presented.&#xD;
Mean hemoglobin increase ≥ 1.5 g/dL - Proportion of subjects achieving hemoglobin (Hgb) increase from baseline ≥ 1.5 g/dL over any consecutive 56-day period in absence of Red blood cell (RBC) transfusions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (RBC Transfusion Independency, HI-N, HI-P, HI-E or Objective Response) (Phase I)</measure>
    <time_frame>From the first date of achieving a response until the date of relapse, up to 168 days (6 cycles, each of 28 days)</time_frame>
    <description>Defined only for patients who achieve complete Response (CR) or marrow complete response (mCR) or RBC Transfusion independency (TI), measured from first date of achieving response until date of relapse. Date of relapse will be earliest of dates of disease assessment (blood sample, bone marrow sample, or clinical assessment) in which relapse was observed. For patients who die or are lost to follow-up without documented relapse, response duration will be censored, respectively, on date of death, regardless of cause, or on date of last disease assessment for patients who are alive when lost to follow-up. Duration of Response [days] = date of outcome - date of first assessment indicating CR or mCR or RBC TI after first administration of trial medication + 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] (Phase I)</measure>
    <time_frame>From first administration of BI 836858 until overall objective response, up to 168 days (6 cycles, each of 28 days)</time_frame>
    <description>Number of patients with overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] is presented.&#xD;
Overall Objective Response is defined as Complete Response (CR), Partial Response (PR), HI-N, HI-P, or HI-E. A patient's &quot; Overall Objective Response &quot; = &quot;Yes&quot; if one of these responses was reported at least once throughout the trial.&#xD;
CR defined as: -Bone marrow: &lt;5 % blasts with normal maturation of all cell lines (Dysplastic changes should consider the normal range of dysplastic changes), persistent dysplasia will be noted; -Peripheral blood: Hgb &gt; 11 grams per deciliters (g/dL), Platelets &gt;100 x 109/liters (L), Neutrophils &gt; 1.0 x 109/L, Blasts 0 % PR defined as: -All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by &gt;50 % to pre-treatment but still &gt;5 %, Cellularity and morphology not relevant.&#xD;
HI Definition see other endpoints.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Myelodysplastic Syndromes</condition>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Best Supportive Care Alone</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BI 836858 plus Best Supportive Care</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Best Supportive Care</intervention_name>
    <description>At Discretion of the Investigator (Transfusions)</description>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 836858</intervention_name>
    <description>Monotherapy with BI 836858</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Documented diagnosis of Myelodysplastic Syndromes (MDS) according to World Health&#xD;
             Organization (WHO) criteria that meets International Prognostic Scoring System (IPSS)&#xD;
             classification of low or intermediate-1 risk disease at screening as determined by&#xD;
             microscopic and standard cytogenetic analyses of the bone marrow and peripheral&#xD;
             complete blood count (CBC).&#xD;
&#xD;
               -  Phase I dose escalation: patients who experienced Erythropoiesis-Stimulating&#xD;
                  Agents (ESA) treatment failure or do not qualify (serum erythropoietin level &gt;&#xD;
                  500 U) for ESA treatment, and are refractory to or not amenable or eligible for&#xD;
                  established MDS therapy (Hypomethylating Agents (HMA), lenalidomide)&#xD;
&#xD;
               -  Phase I expansion:&#xD;
&#xD;
                    -  Expansion cohort 1 (&quot;pre-treated&quot;): patients who experienced ESA treatment&#xD;
                       failure or do not qualify (serum erythropoietin level &gt; 500 U) for ESA&#xD;
                       treatment and are refractory to established MDS therapy (HMA and /or&#xD;
                       lenalidomide)&#xD;
&#xD;
                    -  Expansion cohort 2 (&quot;untreated&quot;): patients who experienced ESA treatment&#xD;
                       failure or do not qualify (serum erythropoietin level &gt; 500 U) for ESA&#xD;
                       treatment and who have not received prior HMA and/or lenalidomide (because&#xD;
                       not amenable or eligible for these treatments).&#xD;
&#xD;
               -  Phase II: patients who experienced ESA treatment failure or do not qualify (serum&#xD;
                  erythropoietin level &gt; 500 U) for ESA treatment. For definition of further&#xD;
                  details of the phase II patients to be included the protocol will be amended&#xD;
                  based on Phase I results&#xD;
&#xD;
          -  Patient is non-responsive to, refractory to, or intolerant of ESAs, or ESAs are&#xD;
             contraindicated or unavailable, or a documented serum erythropoietin level of &gt; 500&#xD;
             U/L.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status &lt;=2.&#xD;
&#xD;
          -  Age &gt;= 18 years.&#xD;
&#xD;
          -  Written informed consent which is consistent with International Conference on&#xD;
             Harmonization - Good Clinical Practice (ICH-GCP) guidelines and local legislation.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Patient with IPSS category of Int-2 or high-risk MDS.&#xD;
&#xD;
          -  Phase II only: Patients with a deletion 5q cytogenetic abnormality.&#xD;
&#xD;
          -  Treatment within 28 days prior to Cycle 1 Day 1 with: i) long acting erythropoiesis&#xD;
             stimulating agents, ii) long acting Granulocyte colony-stimulating factor (G-CSF),&#xD;
             iii) granulocyte- macrophage colony stimulating factor (GM-CSF), iv) 5-aza,&#xD;
             lenalidomide or decitabine, or v) iron chelation and within 14 days prior to Cycle 1&#xD;
             Day 1 with short acting erythropoiesis stimulating agents and short acting G-CSF.&#xD;
&#xD;
          -  Patient previously received allogeneic bone marrow or stem cell transplantation.&#xD;
&#xD;
          -  Second malignancy currently requiring active therapy (except for hormonal/antihormonal&#xD;
             treatment, e.g. in prostate or breast cancer).&#xD;
&#xD;
          -  Aspartate amino transferase (AST) or alanine amino transferase (ALT) &gt; 2.5 times the&#xD;
             upper limit of normal (ULN).&#xD;
&#xD;
          -  Bilirubin &gt;1.5 mg/dL, except for Gilbert's Syndrome or hemolysis.&#xD;
&#xD;
          -  Serum creatinine &gt;2.0 mg/dL.&#xD;
&#xD;
          -  Known human immunodeficiency virus (HIV) infection and/or active hepatitis B infection&#xD;
             (defined as presence of Hep B DNA), active hepatitis C infection (defined as presence&#xD;
             of Hep C RNA).&#xD;
&#xD;
          -  Presence of concomitant intercurrent illness, or any condition which in the opinion of&#xD;
             the Investigator, would compromise safe participation in the study, e.g. active severe&#xD;
             infection, unstable angina pectoris, new onset of exacerbation of a cardiac&#xD;
             arrhythmia.&#xD;
&#xD;
          -  Psychiatric illness or social situation which in the opinion of the Investigator would&#xD;
             limit compliance with trial requirements.&#xD;
&#xD;
          -  Patient receiving concomitant therapy, which in the opinion of the Investigator is&#xD;
             considered relevant for the evaluation of the efficacy or safety of the trial drug.&#xD;
&#xD;
          -  Female patients of childbearing potential who are sexually active and unwilling to use&#xD;
             a medically acceptable method of contraception during the trial and for 6 months after&#xD;
             the last administration of BI 836858, i.e. combination of two forms of effective&#xD;
             contraception (defined as hormonal contraception, intrauterine device, transdermal&#xD;
             patch, implantable or injectable contraceptive, bilateral tubal ligation etc.).&#xD;
&#xD;
        Women of childbearing potential are defined as females who:&#xD;
&#xD;
          -  Have experienced menarche and&#xD;
&#xD;
          -  Are not postmenopausal (12 months with no menses without an alternative medical cause)&#xD;
             and&#xD;
&#xD;
          -  Are not permanently sterilized (e.g. hysterectomy, bilateral oophorectomy or bilateral&#xD;
             salpingectomy&#xD;
&#xD;
               -  Male patients with partners of childbearing potential who are unwilling to use&#xD;
                  condoms in combination with a second effective method of contraception (defined&#xD;
                  as hormonal contraception, intrauterine device, condom with spermicide, etc.)&#xD;
                  during the trial and for 6 months after the last administration of BI 836858.&#xD;
&#xD;
               -  Pregnant or nursing female patients.&#xD;
&#xD;
               -  Treatment with another investigational agent under the following conditions:&#xD;
&#xD;
          -  Within two weeks (4 weeks for biologics) of first administration of BI 836858, or if&#xD;
             the half-life of the previous product is known, within 5 times the half-life,&#xD;
             whichever is longer.&#xD;
&#xD;
          -  Patient has persistent toxicities from prior MDS therapies which are determined to be&#xD;
             relevant by the Investigator.&#xD;
&#xD;
          -  Concomitant treatment with another investigational agent while participating this&#xD;
             trial.&#xD;
&#xD;
               -  Chronic use, as defined by &gt; 2 weeks of a corticosteroid agent that is &gt;= 20&#xD;
                  mg/day of prednisone or its equivalent, within 4 weeks prior to first&#xD;
                  administration of BI 836858.&#xD;
&#xD;
               -  Treatment with an immunomodulatory agent within 4 weeks prior to first&#xD;
                  administration of BI 836858.&#xD;
&#xD;
               -  Patient received prior treatment with a CD33 antibody.&#xD;
&#xD;
               -  In the opinion of the Investigator patient is unable or unwilling to comply with&#xD;
                  the protocol.&#xD;
&#xD;
               -  Further exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</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>Mayo Clinic Cancer Center</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center and Research Institute</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Carl Gustav Carus Dresden</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Düsseldorf</name>
      <address>
        <city>Düsseldorf</city>
        <zip>40225</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <results_first_submitted>November 16, 2020</results_first_submitted>
  <results_first_submitted_qc>December 18, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 21, 2020</results_first_posted>
  <last_update_submitted>December 18, 2020</last_update_submitted>
  <last_update_submitted_qc>December 18, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2020</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>Preleukemia</mesh_term>
    <mesh_term>Myelodysplastic Syndromes</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 7, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT02240706/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 11, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/06/NCT02240706/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This is a phase I/II, multicenter, open-label, dose escalation and randomized trial of BI 836858 in patients with low or intermediate-1 risk myelodysplastic syndromes.</recruitment_details>
      <pre_assignment_details>Subjects were screened for eligibility prior to participation. They attended a specialist site which ensured that they strictly met all eligibility criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>BI 836858 20 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="P2">
          <title>BI 836858 40 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="P3">
          <title>BI 836858 80 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="P4">
          <title>BI 836858 160 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="P5">
          <title>BI 836858 320 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="P6">
          <title>BI 836858 + Best Supportive Care (BSC) (Phase II)</title>
          <description>All patients were planned to be administered doses of BI 836858, recommended phase 2 dose (RP2D) together with best supportive care (BSC) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="P7">
          <title>Best Supportive Care (BSC) Only (Phase II)</title>
          <description>All patients were planned to be administered best supportive care (BSC) including red blood cell transfusion, platelet transfusion and iron chelation therapy.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="11"/>
                <participants group_id="P6" count="0">No patients were enrolled in the Phase II part due to strategic reasons.</participants>
                <participants group_id="P7" count="0">No patients were enrolled in the Phase II part due to strategic reasons.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="11"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="5"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Dose limiting toxicity</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Refused to continue taking medication</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Insurance billing concerns</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated set (TS): The TS included all subjects who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
      <group_list>
        <group group_id="B1">
          <title>BI 836858 20 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="B2">
          <title>BI 836858 40 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="B3">
          <title>BI 836858 80 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="B4">
          <title>BI 836858 160 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="B5">
          <title>BI 836858 320 mg (Phase I)</title>
          <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="B6">
          <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="3"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="4"/>
            <count group_id="B5" value="11"/>
            <count group_id="B6" value="27"/>
          </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="71.0" spread="5.57"/>
                    <measurement group_id="B2" value="75.0" spread="6.24"/>
                    <measurement group_id="B3" value="73.8" spread="16.41"/>
                    <measurement group_id="B4" value="68.3" spread="12.18"/>
                    <measurement group_id="B5" value="75.6" spread="5.08"/>
                    <measurement group_id="B6" value="73.6" spread="9.56"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="11"/>
                    <measurement group_id="B6" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="11"/>
                    <measurement group_id="B6" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Tolerated Dose (MTD) (Phase I)</title>
        <description>The MTD is defined as the highest dose of BI 836858 with less than 25% risk of the true dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period. MTD determination will be based on a Bayesian logistic regression model with overdose control.&#xD;
For any dose-escalation cohort, at least 3 patients (pts) will be required. However, in the case that only 2 pts are evaluable and neither has experienced a DLT within the first cycle (2 administrations - 28 days), then dose-escalation can occur based on these 2 pts. After all pts in a cohort have either experienced a DLT or have been observed for at least one cycle (2 administrations - 28 days) without experiencing a DLT, the Bayesian model will be updated with the newly accumulated data.&#xD;
The MTD may be considered reached if either the posterior probability of the true DLT rate in the target interval (16%-33%) is above 50%, or at least 12 pts have been treated at MTD, including the two expansion cohorts.</description>
        <time_frame>From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days</time_frame>
        <population>As the study was prematurely discontinued, recruitment of participants into the dose escalation part was not fully completed. No formal MTD was determined.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858</title>
            <description>Treatment group &quot;BI 836858&quot; comprises all dose cohorts during the dose escalation phase, that is, &quot;BI 836858 20 mg&quot;, &quot;BI 836858 40 mg&quot;, &quot;BI 836858 80 mg&quot;, &quot;BI 836858 160 mg&quot; and &quot;BI 836858 320 mg&quot;.&#xD;
All patients were administered doses of BI 836858, by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Tolerated Dose (MTD) (Phase I)</title>
          <description>The MTD is defined as the highest dose of BI 836858 with less than 25% risk of the true dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period. MTD determination will be based on a Bayesian logistic regression model with overdose control.&#xD;
For any dose-escalation cohort, at least 3 patients (pts) will be required. However, in the case that only 2 pts are evaluable and neither has experienced a DLT within the first cycle (2 administrations - 28 days), then dose-escalation can occur based on these 2 pts. After all pts in a cohort have either experienced a DLT or have been observed for at least one cycle (2 administrations - 28 days) without experiencing a DLT, the Bayesian model will be updated with the newly accumulated data.&#xD;
The MTD may be considered reached if either the posterior probability of the true DLT rate in the target interval (16%-33%) is above 50%, or at least 12 pts have been treated at MTD, including the two expansion cohorts.</description>
          <population>As the study was prematurely discontinued, recruitment of participants into the dose escalation part was not fully completed. No formal MTD was determined.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Dose Limiting Toxicity (DLT) (Phase I)</title>
        <description>Dose Limiting Toxicity (DLT):&#xD;
Grade (G) ≥ 3 (CTCAE 4.0), non disease-related, non-hematologic adverse events (AE), except:&#xD;
Laboratory abnormality, not significant by investigator or resolves spontaneously or can be recovered with appropriate treatment (T) within 5 d&#xD;
Neutrophils (NP) &lt;500 /microliters (μL) at T start, febrile neutropenia with NP &lt;500 /μL or infection with NP &lt;500 /μL will not constitute a DLT if they can be recovered with appropriate T within 14 d&#xD;
Inability to deliver study drug full dose according to the assigned dose level within cycle 1 due to drug-related AEs&#xD;
Absence of hematological recovery as following:&#xD;
NPs: G 4 (if G 0/1 at baseline (BL)) OR &lt;100 /μL and decrease of &gt;75% from BL (if G ≥2 at BL) for &gt;7 d&#xD;
Platelets: G 4 (if G 0/1 at BL) OR &lt; 10000/μL for &gt;7 d and decrease of &gt;75% from BL (if G ≥2 at BL)&#xD;
T delay of ≥4 weeks of start of Cycle 2 --If Cycle 2 is not started until 57th d as a result of drug related AE, it is considered as DLT</description>
        <time_frame>From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days</time_frame>
        <population>MTD evaluation set: All patients who were documented to have initiated at least one dose of BI 836858 and who have not been replaced for the MTD evaluation.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 20 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>BI 836858 40 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O3">
            <title>BI 836858 80 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O4">
            <title>BI 836858 160 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O5">
            <title>BI 836858 320 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Dose Limiting Toxicity (DLT) (Phase I)</title>
          <description>Dose Limiting Toxicity (DLT):&#xD;
Grade (G) ≥ 3 (CTCAE 4.0), non disease-related, non-hematologic adverse events (AE), except:&#xD;
Laboratory abnormality, not significant by investigator or resolves spontaneously or can be recovered with appropriate treatment (T) within 5 d&#xD;
Neutrophils (NP) &lt;500 /microliters (μL) at T start, febrile neutropenia with NP &lt;500 /μL or infection with NP &lt;500 /μL will not constitute a DLT if they can be recovered with appropriate T within 14 d&#xD;
Inability to deliver study drug full dose according to the assigned dose level within cycle 1 due to drug-related AEs&#xD;
Absence of hematological recovery as following:&#xD;
NPs: G 4 (if G 0/1 at baseline (BL)) OR &lt;100 /μL and decrease of &gt;75% from BL (if G ≥2 at BL) for &gt;7 d&#xD;
Platelets: G 4 (if G 0/1 at BL) OR &lt; 10000/μL for &gt;7 d and decrease of &gt;75% from BL (if G ≥2 at BL)&#xD;
T delay of ≥4 weeks of start of Cycle 2 --If Cycle 2 is not started until 57th d as a result of drug related AE, it is considered as DLT</description>
          <population>MTD evaluation set: All patients who were documented to have initiated at least one dose of BI 836858 and who have not been replaced for the MTD evaluation.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase I)</title>
        <description>Number of patients with red blood cell (RBC) Transfusion Independency is presented.&#xD;
Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator.&#xD;
A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent.&#xD;
A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days.</description>
        <time_frame>From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days)</time_frame>
        <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 20 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>BI 836858 40 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O3">
            <title>BI 836858 80 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O4">
            <title>BI 836858 160 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O5">
            <title>BI 836858 320 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase I)</title>
          <description>Number of patients with red blood cell (RBC) Transfusion Independency is presented.&#xD;
Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator.&#xD;
A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent.&#xD;
A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days.</description>
          <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Hematologic Improvement Neutrophils (HI-N) (Phase I)</title>
        <description>Number of patients with hematologic improvement neutrophils (HI-N) is presented.&#xD;
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:&#xD;
Neutrophil response (HI-N) - Patients with a pretreatment neutrophil count &lt;1 x 10^9/liters (L) demonstrate a neutrophil response if they have an at least 100 percent increase and an absolute increase &gt;0.5 x 10^9/L.</description>
        <time_frame>From first administration of BI 836858 until HI-N, up to 168 days (6 cycles, each of 28 days)</time_frame>
        <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 20 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>BI 836858 40 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O3">
            <title>BI 836858 80 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O4">
            <title>BI 836858 160 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O5">
            <title>BI 836858 320 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Hematologic Improvement Neutrophils (HI-N) (Phase I)</title>
          <description>Number of patients with hematologic improvement neutrophils (HI-N) is presented.&#xD;
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:&#xD;
Neutrophil response (HI-N) - Patients with a pretreatment neutrophil count &lt;1 x 10^9/liters (L) demonstrate a neutrophil response if they have an at least 100 percent increase and an absolute increase &gt;0.5 x 10^9/L.</description>
          <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Hematologic Improvement Platelets (HI-P) (Phase I)</title>
        <description>Number of patients with hematologic improvement platelets (HI-P) is presented.&#xD;
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:&#xD;
Platelet response (HI-P) - Patients with a pretreatment platelet count &lt;100 x 109/Liters (L) demonstrate a platelet response if there is an absolute platelet increase of ≥30 x 109/L for patients starting with &gt;20 x 109/L platelets. For those with an increase from 10 x 109/L to &gt;20 x 109/L must have an increase of at least 100 percent.</description>
        <time_frame>From first administration of BI 836858 until HI-P, up to 168 days (6 cycles, each of 28 days)</time_frame>
        <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 20 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>BI 836858 40 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O3">
            <title>BI 836858 80 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O4">
            <title>BI 836858 160 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O5">
            <title>BI 836858 320 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Hematologic Improvement Platelets (HI-P) (Phase I)</title>
          <description>Number of patients with hematologic improvement platelets (HI-P) is presented.&#xD;
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:&#xD;
Platelet response (HI-P) - Patients with a pretreatment platelet count &lt;100 x 109/Liters (L) demonstrate a platelet response if there is an absolute platelet increase of ≥30 x 109/L for patients starting with &gt;20 x 109/L platelets. For those with an increase from 10 x 109/L to &gt;20 x 109/L must have an increase of at least 100 percent.</description>
          <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Hematologic Improvement Erythroid (HI-E) (Phase I)</title>
        <description>Number of patients with hematologic improvement erythroid (HI-E) is presented.&#xD;
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:&#xD;
Erythroid response (HI-E): Patients with a pretreatment hemoglobin &lt;11 grams per deciliters (g/dL) demonstrate erythroid response if their hemoglobin increases by ≥1.5 g/dL for at least eight weeks, and there is a reduction in the units of red cell transfusions by an absolute number of at least four red cell transfusions per eight weeks compared with the pretreatment transfusion number in the previous eight weeks. Only red cell transfusions given for a hemoglobin ≤9 g/dL pretreatment will count in the red cell transfusion response evaluation.</description>
        <time_frame>From first administration of BI 836858 until HI-E, up to 168 days (6 cycles, each of 28 days)</time_frame>
        <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 20 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>BI 836858 40 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O3">
            <title>BI 836858 80 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O4">
            <title>BI 836858 160 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O5">
            <title>BI 836858 320 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Hematologic Improvement Erythroid (HI-E) (Phase I)</title>
          <description>Number of patients with hematologic improvement erythroid (HI-E) is presented.&#xD;
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:&#xD;
Erythroid response (HI-E): Patients with a pretreatment hemoglobin &lt;11 grams per deciliters (g/dL) demonstrate erythroid response if their hemoglobin increases by ≥1.5 g/dL for at least eight weeks, and there is a reduction in the units of red cell transfusions by an absolute number of at least four red cell transfusions per eight weeks compared with the pretreatment transfusion number in the previous eight weeks. Only red cell transfusions given for a hemoglobin ≤9 g/dL pretreatment will count in the red cell transfusion response evaluation.</description>
          <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to HI-E Response (Phase I)</title>
        <description>Time to HI-E response is defined only for patients who achieve a HI-E response as follows: Time to HI-E response [days] = date of first assessment indicating HI-E response - date of first administration of trial medication + 1.</description>
        <time_frame>From first administration of BI 836858 until HI-E response, up to 168 days (6 cycles, each of 28 days)</time_frame>
        <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. Only patients who showed a HI-E response were included.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 20 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>BI 836858 40 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O3">
            <title>BI 836858 80 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O4">
            <title>BI 836858 160 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O5">
            <title>BI 836858 320 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to HI-E Response (Phase I)</title>
          <description>Time to HI-E response is defined only for patients who achieve a HI-E response as follows: Time to HI-E response [days] = date of first assessment indicating HI-E response - date of first administration of trial medication + 1.</description>
          <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. Only patients who showed a HI-E response were included.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Mean Hemoglobin Increase ≥ 1.5 g/dL (Phase I)</title>
        <description>Number of patients with mean hemoglobin increase ≥ 1.5 grams per deciliters (g/dL) is presented.&#xD;
Mean hemoglobin increase ≥ 1.5 g/dL - Proportion of subjects achieving hemoglobin (Hgb) increase from baseline ≥ 1.5 g/dL over any consecutive 56-day period in absence of Red blood cell (RBC) transfusions.</description>
        <time_frame>Up to 48 weeks</time_frame>
        <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 20 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>BI 836858 40 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O3">
            <title>BI 836858 80 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O4">
            <title>BI 836858 160 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O5">
            <title>BI 836858 320 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Mean Hemoglobin Increase ≥ 1.5 g/dL (Phase I)</title>
          <description>Number of patients with mean hemoglobin increase ≥ 1.5 grams per deciliters (g/dL) is presented.&#xD;
Mean hemoglobin increase ≥ 1.5 g/dL - Proportion of subjects achieving hemoglobin (Hgb) increase from baseline ≥ 1.5 g/dL over any consecutive 56-day period in absence of Red blood cell (RBC) transfusions.</description>
          <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (RBC Transfusion Independency, HI-N, HI-P, HI-E or Objective Response) (Phase I)</title>
        <description>Defined only for patients who achieve complete Response (CR) or marrow complete response (mCR) or RBC Transfusion independency (TI), measured from first date of achieving response until date of relapse. Date of relapse will be earliest of dates of disease assessment (blood sample, bone marrow sample, or clinical assessment) in which relapse was observed. For patients who die or are lost to follow-up without documented relapse, response duration will be censored, respectively, on date of death, regardless of cause, or on date of last disease assessment for patients who are alive when lost to follow-up. Duration of Response [days] = date of outcome - date of first assessment indicating CR or mCR or RBC TI after first administration of trial medication + 1.</description>
        <time_frame>From the first date of achieving a response until the date of relapse, up to 168 days (6 cycles, each of 28 days)</time_frame>
        <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. Only patients who had achieved complete response (CR) or marrow complete response (mCR) or RBC Transfusion independency (TI) were included.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 20 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>BI 836858 40 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O3">
            <title>BI 836858 80 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O4">
            <title>BI 836858 160 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O5">
            <title>BI 836858 320 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (RBC Transfusion Independency, HI-N, HI-P, HI-E or Objective Response) (Phase I)</title>
          <description>Defined only for patients who achieve complete Response (CR) or marrow complete response (mCR) or RBC Transfusion independency (TI), measured from first date of achieving response until date of relapse. Date of relapse will be earliest of dates of disease assessment (blood sample, bone marrow sample, or clinical assessment) in which relapse was observed. For patients who die or are lost to follow-up without documented relapse, response duration will be censored, respectively, on date of death, regardless of cause, or on date of last disease assessment for patients who are alive when lost to follow-up. Duration of Response [days] = date of outcome - date of first assessment indicating CR or mCR or RBC TI after first administration of trial medication + 1.</description>
          <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses. Only patients who had achieved complete response (CR) or marrow complete response (mCR) or RBC Transfusion independency (TI) were included.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
                <count group_id="O5" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] (Phase I)</title>
        <description>Number of patients with overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] is presented.&#xD;
Overall Objective Response is defined as Complete Response (CR), Partial Response (PR), HI-N, HI-P, or HI-E. A patient's &quot; Overall Objective Response &quot; = &quot;Yes&quot; if one of these responses was reported at least once throughout the trial.&#xD;
CR defined as: -Bone marrow: &lt;5 % blasts with normal maturation of all cell lines (Dysplastic changes should consider the normal range of dysplastic changes), persistent dysplasia will be noted; -Peripheral blood: Hgb &gt; 11 grams per deciliters (g/dL), Platelets &gt;100 x 109/liters (L), Neutrophils &gt; 1.0 x 109/L, Blasts 0 % PR defined as: -All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by &gt;50 % to pre-treatment but still &gt;5 %, Cellularity and morphology not relevant.&#xD;
HI Definition see other endpoints.</description>
        <time_frame>From first administration of BI 836858 until overall objective response, up to 168 days (6 cycles, each of 28 days)</time_frame>
        <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 20 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>BI 836858 40 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O3">
            <title>BI 836858 80 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O4">
            <title>BI 836858 160 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O5">
            <title>BI 836858 320 mg (Phase I)</title>
            <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] (Phase I)</title>
          <description>Number of patients with overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] is presented.&#xD;
Overall Objective Response is defined as Complete Response (CR), Partial Response (PR), HI-N, HI-P, or HI-E. A patient's &quot; Overall Objective Response &quot; = &quot;Yes&quot; if one of these responses was reported at least once throughout the trial.&#xD;
CR defined as: -Bone marrow: &lt;5 % blasts with normal maturation of all cell lines (Dysplastic changes should consider the normal range of dysplastic changes), persistent dysplasia will be noted; -Peripheral blood: Hgb &gt; 11 grams per deciliters (g/dL), Platelets &gt;100 x 109/liters (L), Neutrophils &gt; 1.0 x 109/L, Blasts 0 % PR defined as: -All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by &gt;50 % to pre-treatment but still &gt;5 %, Cellularity and morphology not relevant.&#xD;
HI Definition see other endpoints.</description>
          <population>Treated set (TS): The TS included all patients who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase II)</title>
        <description>Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator.&#xD;
A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent.&#xD;
A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days.</description>
        <time_frame>From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days)</time_frame>
        <population>No patients were enrolled in the Phase II part. The company decided to stop the clinical development of BI 836858 prematurely during the Phase I expansion cohort stage for strategic reasons.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 836858 + Best Supportive Care (BSC) (Phase II)</title>
            <description>All patients were planned to be administered doses of BI 836858, recommended phase 2 dose (RP2D) together with best supportive care (BSC) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
          </group>
          <group group_id="O2">
            <title>Best Supportive Care (BSC) Only (Phase II)</title>
            <description>All patients were planned to be administered best supportive care (BSC) including red blood cell transfusion, platelet transfusion and iron chelation therapy.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase II)</title>
          <description>Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator.&#xD;
A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent.&#xD;
A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days.</description>
          <population>No patients were enrolled in the Phase II part. The company decided to stop the clinical development of BI 836858 prematurely during the Phase I expansion cohort stage for strategic reasons.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first administration of BI 836858 until end of residual effect period (REP), up to 198 days. For all-cause mortality from first administration of BI 836858 until end of follow-up, up to 198 days + 6 months follow-up.</time_frame>
      <desc>Treated set (TS): The TS included all subjects who had been enrolled and treated with at least 1 dose of study drug. The treated set was used for safety analyses.</desc>
      <group_list>
        <group group_id="E1">
          <title>BI 836858 20mg</title>
          <description>All patients were administered doses of BI 836858, 20 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="E2">
          <title>BI 836858 40mg</title>
          <description>All patients were administered doses of BI 836858, 40 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="E3">
          <title>BI 836858 80mg</title>
          <description>All patients were administered doses of BI 836858, 80 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="E4">
          <title>BI 836858 160mg</title>
          <description>All patients were administered doses of BI 836858, 160 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
        <group group_id="E5">
          <title>BI 836858 320mg</title>
          <description>All patients were administered doses of BI 836858, 320 milligrams (mg) by a rate-controlled intravenous infusion on day 1 and on day 15 of a 28-day cycle for a duration of 4 cycles. All infusions were to be started at a rate of 10 mL/h. The infusion rate was to be increased every 30 (+/-10) minutes by 10 mL/h to a maximum of 80 mL/h as long as tolerated by the patient.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Ventricular tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Enterocolitis infectious</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </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="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Subdural haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Lung infiltration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22.1</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="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Monocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Atrioventricular block first degree</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Anal incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Faeces discoloured</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hiatus hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Arthritis infective</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Diverticulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Enterococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Postoperative wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Staphylococcal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tinea cruris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Tinea pedis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Scratch</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Skin abrasion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Spinal fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Carotid bruit</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>QRS axis abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Iron overload</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </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="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary incontinence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Petechiae</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Skin burning sensation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Skin induration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hot flush</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="11"/>
              </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>Development of BI 836858 was discontinued (strategic decision) during the Phase I Expansion cohort stage. No patients were enrolled in the Phase II part.</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/NCT02240706
org study id: 1315.7
secondary id: 2018-002177-21
nct id: NCT02240706
lead sponsor: 
Phase I: To investigate maximum tolerated dose (MTD), safety and tolerability,
      pharmacokinetics, exploratory biomarker and efficacy of BI 836858 monotherapy in patients
      with low or intermediate-1 risk myelodysplastic syndromes (MDS) with symptomatic anemia.
      Phase II: To investigate safety and efficacy of BI 836858 plus Best Supportive Care compared
      to Best Supportive Care alone in low or intermediate-1 risk MDS patients with symptomatic
      anemia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) (Phase I)
time frame: From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days
description: The MTD is defined as the highest dose of BI 836858 with less than 25% risk of the true dose-limiting toxicity (DLT) rate being above 33% during the MTD evaluation period. MTD determination will be based on a Bayesian logistic regression model with overdose control.
For any dose-escalation cohort, at least 3 patients (pts) will be required. However, in the case that only 2 pts are evaluable and neither has experienced a DLT within the first cycle (2 administrations - 28 days), then dose-escalation can occur based on these 2 pts. After all pts in a cohort have either experienced a DLT or have been observed for at least one cycle (2 administrations - 28 days) without experiencing a DLT, the Bayesian model will be updated with the newly accumulated data.
The MTD may be considered reached if either the posterior probability of the true DLT rate in the target interval (16%-33%) is above 50%, or at least 12 pts have been treated at MTD, including the two expansion cohorts.
measure: Number of Patients With Dose Limiting Toxicity (DLT) (Phase I)
time frame: From the first administration of BI 836858 to start of the third administration of BI 836858, excluding the day of the third administration of BI 836858, up to 28 days
description: Dose Limiting Toxicity (DLT):
Grade (G) ≥ 3 (CTCAE 4.0), non disease-related, non-hematologic adverse events (AE), except:
Laboratory abnormality, not significant by investigator or resolves spontaneously or can be recovered with appropriate treatment (T) within 5 d
Neutrophils (NP) <500 /microliters (μL) at T start, febrile neutropenia with NP <500 /μL or infection with NP <500 /μL will not constitute a DLT if they can be recovered with appropriate T within 14 d
Inability to deliver study drug full dose according to the assigned dose level within cycle 1 due to drug-related AEs
Absence of hematological recovery as following:
NPs: G 4 (if G 0/1 at baseline (BL)) OR <100 /μL and decrease of >75% from BL (if G ≥2 at BL) for >7 d
Platelets: G 4 (if G 0/1 at BL) OR < 10000/μL for >7 d and decrease of >75% from BL (if G ≥2 at BL)
T delay of ≥4 weeks of start of Cycle 2 --If Cycle 2 is not started until 57th d as a result of drug related AE, it is considered as DLT
measure: Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase II)
time frame: From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days)
description: Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator.
A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent.
A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days.
measure: Number of Patients With Red Blood Cell (RBC) Transfusion Independency (Phase I)
time frame: From first administration of BI 836858 until discontinuation of the treatment. Up to 168 days (6 cycles, each of 28 days)
description: Number of patients with red blood cell (RBC) Transfusion Independency is presented.
Red blood cell (RBC) transfusion independence and platelet transfusion independence will be evaluated in patients who are transfusion dependent at baseline. Percentages will be calculated using all treated patients as the denominator.
A patient is considered transfusion independent at baseline if the patient has had no transfusions during the 56 days prior to and including the first day of treatment. Otherwise, the patient is considered to be transfusion dependent.
A patient is considered transfusion independent if the patient has had no transfusions over the course of ≥ 56 consecutive days.
measure: Number of Patients With Hematologic Improvement Neutrophils (HI-N) (Phase I)
time frame: From first administration of BI 836858 until HI-N, up to 168 days (6 cycles, each of 28 days)
description: Number of patients with hematologic improvement neutrophils (HI-N) is presented.
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:
Neutrophil response (HI-N) - Patients with a pretreatment neutrophil count <1 x 10^9/liters (L) demonstrate a neutrophil response if they have an at least 100 percent increase and an absolute increase >0.5 x 10^9/L.
measure: Number of Patients With Hematologic Improvement Platelets (HI-P) (Phase I)
time frame: From first administration of BI 836858 until HI-P, up to 168 days (6 cycles, each of 28 days)
description: Number of patients with hematologic improvement platelets (HI-P) is presented.
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:
Platelet response (HI-P) - Patients with a pretreatment platelet count <100 x 109/Liters (L) demonstrate a platelet response if there is an absolute platelet increase of ≥30 x 109/L for patients starting with >20 x 109/L platelets. For those with an increase from 10 x 109/L to >20 x 109/L must have an increase of at least 100 percent.
measure: Number of Patients With Hematologic Improvement Erythroid (HI-E) (Phase I)
time frame: From first administration of BI 836858 until HI-E, up to 168 days (6 cycles, each of 28 days)
description: Number of patients with hematologic improvement erythroid (HI-E) is presented.
The HI will be evaluated in patients with abnormal pretreatment values defined as follows:
Erythroid response (HI-E): Patients with a pretreatment hemoglobin <11 grams per deciliters (g/dL) demonstrate erythroid response if their hemoglobin increases by ≥1.5 g/dL for at least eight weeks, and there is a reduction in the units of red cell transfusions by an absolute number of at least four red cell transfusions per eight weeks compared with the pretreatment transfusion number in the previous eight weeks. Only red cell transfusions given for a hemoglobin ≤9 g/dL pretreatment will count in the red cell transfusion response evaluation.
measure: Time to HI-E Response (Phase I)
time frame: From first administration of BI 836858 until HI-E response, up to 168 days (6 cycles, each of 28 days)
description: Time to HI-E response is defined only for patients who achieve a HI-E response as follows: Time to HI-E response [days] = date of first assessment indicating HI-E response - date of first administration of trial medication + 1.
measure: Number of Patients With Mean Hemoglobin Increase ≥ 1.5 g/dL (Phase I)
time frame: Up to 48 weeks
description: Number of patients with mean hemoglobin increase ≥ 1.5 grams per deciliters (g/dL) is presented.
Mean hemoglobin increase ≥ 1.5 g/dL - Proportion of subjects achieving hemoglobin (Hgb) increase from baseline ≥ 1.5 g/dL over any consecutive 56-day period in absence of Red blood cell (RBC) transfusions.
measure: Duration of Response (RBC Transfusion Independency, HI-N, HI-P, HI-E or Objective Response) (Phase I)
time frame: From the first date of achieving a response until the date of relapse, up to 168 days (6 cycles, each of 28 days)
description: Defined only for patients who achieve complete Response (CR) or marrow complete response (mCR) or RBC Transfusion independency (TI), measured from first date of achieving response until date of relapse. Date of relapse will be earliest of dates of disease assessment (blood sample, bone marrow sample, or clinical assessment) in which relapse was observed. For patients who die or are lost to follow-up without documented relapse, response duration will be censored, respectively, on date of death, regardless of cause, or on date of last disease assessment for patients who are alive when lost to follow-up. Duration of Response [days] = date of outcome - date of first assessment indicating CR or mCR or RBC TI after first administration of trial medication + 1.
measure: Number of Patients With Overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] (Phase I)
time frame: From first administration of BI 836858 until overall objective response, up to 168 days (6 cycles, each of 28 days)
description: Number of patients with overall Objective Response (OR) [Complete Response (CR), Partial Response (PR), and Hematologic Improvement (HI)] is presented.
Overall Objective Response is defined as Complete Response (CR), Partial Response (PR), HI-N, HI-P, or HI-E. A patient's " Overall Objective Response " = "Yes" if one of these responses was reported at least once throughout the trial.
CR defined as: -Bone marrow: <5 % blasts with normal maturation of all cell lines (Dysplastic changes should consider the normal range of dysplastic changes), persistent dysplasia will be noted; -Peripheral blood: Hgb > 11 grams per deciliters (g/dL), Platelets >100 x 109/liters (L), Neutrophils > 1.0 x 109/L, Blasts 0 % PR defined as: -All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by >50 % to pre-treatment but still >5 %, Cellularity and morphology not relevant.
HI Definition see other endpoints.
arm group label: Arm B
arm group type: Active Comparator
description: Best Supportive Care Alone
arm group label: Arm A
arm group type: Experimental
description: BI 836858 plus Best Supportive Care
intervention type: Procedure
intervention name: Best Supportive Care
description: At Discretion of the Investigator (Transfusions)
arm group label: Arm A
arm group label: Arm B
intervention type: Drug
intervention name: BI 836858
description: Monotherapy with BI 836858
arm group label: Arm A
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: United States
url: https://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Preleukemia
mesh term: Myelodysplastic Syndromes
mesh term: Syndrome
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Development of BI 836858 was discontinued (strategic decision) during the Phase I Expansion cohort stage. No patients were enrolled in the Phase II part.
point of contact: 