<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/NCT01677858</url>
  </required_header>
  <id_info>
    <org_study_id>2012-002</org_study_id>
    <secondary_id>20130403</secondary_id>
    <nct_id>NCT01677858</nct_id>
  </id_info>
  <brief_title>A Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma</brief_title>
  <acronym>CHAMPION 1</acronym>
  <official_title>A Phase 1/2 Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Amgen</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Amgen</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study had the following primary objectives:&#xD;
&#xD;
        -  Phase 1: to determine the maximum tolerated dose (MTD) of once-weekly (QW) carfilzomib&#xD;
           and dexamethasone for patients with relapsed or refractory multiple myeloma who have&#xD;
           received 1 to 3 prior therapies&#xD;
&#xD;
        -  Phase 2: to estimate the overall response rate (ORR) for patients with relapsed or&#xD;
           refractory multiple myeloma who received 1 to 3 prior therapies treated with carfilzomib&#xD;
           and dexamethasone QW at the MTD established in phase 1.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1/2, multicenter, single-arm, nonrandomized, open-label and dose-escalation&#xD;
      study of weekly carfilzomib and dexamethasone for patients with progressive multiple myeloma.&#xD;
      The Phase 1 dose escalation portion will enroll patients into sequential dose-escalating&#xD;
      cohorts consisting of 3 patients each to establish the maximum tolerated dose (MTD) of&#xD;
      carfilzomib administered weekly as a 30 minute intravenous (IV) infusion with dexamethasone.&#xD;
      The Phase 2 portion will enroll patients using the MTD established for carfilzomib from the&#xD;
      Phase 1 portion of the study. Dexamethasone will be administered IV or orally at the same&#xD;
      dose and schedule as used in the Phase 1 portion of the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 4, 2012</start_date>
  <completion_date type="Actual">October 31, 2018</completion_date>
  <primary_completion_date type="Actual">July 22, 2016</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)</measure>
    <time_frame>28 days</time_frame>
    <description>The MTD was defined as the highest carfilzomib dose at which &lt; 33% of participants had a treatment-related DLT during the first 28-day cycle. A DLT was categorized as nonhematologic or hematologic and defined as follows:&#xD;
Nonhematologic:&#xD;
≥ grade 3 nonhematological toxicity (excluding nausea, vomiting, diarrhea, fatigue lasting &lt; 14 days, increased serum creatinine or electrolyte abnormalities not clinically significant or requiring treatment)&#xD;
≥ grade 3 acute kidney injury (creatinine &gt; 3 x baseline or &gt; 4.0 mg/dL) lasting &gt; 72 hours&#xD;
≥ grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy&#xD;
Hematologic:&#xD;
grade 4 neutropenia (absolute neutrophil count [ANC] &lt; 500/mm³) for &gt; 7 days&#xD;
febrile neutropenia (ANC &lt; 1000/mm³ with a fever ≥ 38.3ºC) of any duration&#xD;
grade 4 thrombocytopenia (&lt; 25 000/mm³) for &gt; 14 days, despite holding treatment&#xD;
grade 3 or 4 thrombocytopenia (&lt; lower limit of normal) associated with &gt; grade 1 bleeding</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.</time_frame>
    <description>Disease response was evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). ORR was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).&#xD;
sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).&#xD;
CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and &lt; 5% plasma cells in BM.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein &lt;100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.&#xD;
PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to &lt; 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Response Rate</measure>
    <time_frame>Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.</time_frame>
    <description>Clinical benefit rate was defined as the percentage of participants whose best response was sCR, CR, VGPR, PR, or minimal response (MR), where MR is defined by the European Group for Blood and Marrow Transplant (EBMT) criteria as a 25% to 49% reduction in the level of serum M-protein or a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour, maintained for a minimum of 8 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>From randomization until the data cut-off date of 22 July 2016; median follow-up time for PFS was 13.8 months</time_frame>
    <description>Progression-free survival (PFS) was defined as the time from first dose to the earlier of disease progression or death due to any cause. The duration of PFS was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.&#xD;
Participants were evaluated for disease response and progression by the investigator according to the IMWG-URC.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time To Progression</measure>
    <time_frame>From randomization until the data cut-off date of 22 July 2016; median follow-up time for TTP was 13.4 months</time_frame>
    <description>Time to progression (TTP) was defined as the time from first dose to disease progression evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). TTP was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>From randomization until the data cut-off date of 22 July 2016; median follow-up time for DOR was 14.3 months</time_frame>
    <description>Duration of response (DOR) was defined as the time from first evidence of PR or better to disease progression or death due to any cause. DOR was calculated using Kaplan-Meier methods; Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>From the first day of study treatment and within 30 days of the last day of study treatment; median duration of treatment was 33.6 weeks.</time_frame>
    <description>Adverse events were graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (version 4.03).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Plasma Concentration of Carfilzomib</measure>
    <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration of Carfilzomib</measure>
    <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Carfilzomib</measure>
    <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) fo Carfilzomib</measure>
    <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve During the Dosing Interval (0-168 Hours) for Carfilzomib</measure>
    <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution Observed at Steady State (Vss) for Carfilzomib</measure>
    <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-life (T1/2,z) for Carfilzomib</measure>
    <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance of Carfilzomib After IV Infusion</measure>
    <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Residence Time Observed From Time Zero to Infinity (MRT0-∞) for Carfilzomib</measure>
    <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">116</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Carfilzomib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In phase 1 participants were assigned to one of four sequential dose-escalating cohorts to receive 45, 56, 70 or 88 mg/m² carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.&#xD;
In phase 2 participants received carfilzomib at the maximum tolerated dose (MTD) established in the Phase 1 portion of the study on days 1, 8 and 15 plus 40 mg dexamethasone IV or orally at the same schedule as used in the Phase 1 portion of the study.&#xD;
Participants were treated until confirmed progressive disease, unacceptable toxicity, withdrew consent for further treatment, were lost to follow-up, died, or the sponsor closed the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carfilzomib</intervention_name>
    <description>Carfilzomib was administered as a 30-minute IV infusion on days 1, 8, and 15 of each 28-day treatment cycle.</description>
    <arm_group_label>Carfilzomib</arm_group_label>
    <other_name>Krypolis</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexamethasone</intervention_name>
    <description>Dexamethasone was administered at a dose of 40 mg IV or orally (PO) on days 1, 8, 15, and 22 for the first 8 cycles; starting with cycle 9 dexamethasone was administered on days 1, 8, and 15.</description>
    <arm_group_label>Carfilzomib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Multiple myeloma with relapsing or progressive disease at study entry&#xD;
&#xD;
          2. Measurable disease, as defined by 1 or more of the following (assessed within 21 days&#xD;
             prior to enrollment):&#xD;
&#xD;
               1. Serum M-protein ≥ 0.5 g/dL, or&#xD;
&#xD;
               2. Urine M-protein ≥ 200 mg/24 hours, or&#xD;
&#xD;
               3. Only in patients who do not meet a or b, then use serum free light chain (SFLC) &gt;&#xD;
                  100 mg/L (involved light chain) and an abnormal kappa/lambda ratio&#xD;
&#xD;
          3. Prior treatment with 1 to 3 prior regimens for multiple myeloma for Phase 1 and Phase&#xD;
             2 (induction therapy followed by stem cell transplant and consolidation/maintenance&#xD;
             therapy will be considered as 1 line of therapy&#xD;
&#xD;
          4. Age ≥ 18 years&#xD;
&#xD;
          5. Life expectancy ≥ 6 months&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
&#xD;
          7. Adequate hepatic function within 21 days prior to enrollment, with bilirubin &lt; 1.5 ×&#xD;
             the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine&#xD;
             aminotransferase (ALT) &lt; 3 × ULN&#xD;
&#xD;
          8. Left ventricular ejection fraction (LVEF) ≥ 40%. 2-D transthoracic echocardiogram&#xD;
             (ECHO) is the preferred method of evaluation. Multigated acquisition scan (MUGA) is&#xD;
             acceptable if ECHO is not available&#xD;
&#xD;
          9. Absolute neutrophil count (ANC) ≥ 1000/mm³ within 21 days prior to enrollment.&#xD;
             Screening ANC is to be independent of growth factor support for ≥ 1 week&#xD;
&#xD;
         10. Hemoglobin ≥ 8.0 g/dL within 21 days prior to enrollment. Use of erythropoietic&#xD;
             stimulating factors and red blood cell (RBC) transfusions per institutional guidelines&#xD;
             is allowed; however, most recent RBC transfusion must have been at least 7 days prior&#xD;
             to obtaining screening hemoglobin&#xD;
&#xD;
         11. Platelet count ≥ 50,000/mm³ (≥ 30,000/mm³ if myeloma involvement in the bone marrow is&#xD;
             &gt; 50%) within 21 days prior to enrollment. Patients must not have received platelet&#xD;
             transfusions for at least 7 days prior to obtaining the screening platelet count&#xD;
&#xD;
         12. Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min within 21 days prior&#xD;
             to enrollment. Calculation based on standard formula, such as the Cockcroft and Gault:&#xD;
             [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female&#xD;
&#xD;
         13. Written informed consent in accordance with federal, local, and institutional&#xD;
             guidelines&#xD;
&#xD;
         14. Female patients of childbearing potential (FCBP) must have a negative serum pregnancy&#xD;
             test within 21 days prior to enrollment and agree to use an effective method of&#xD;
             contraception during and for 3 months following last dose of drug (more frequent&#xD;
             pregnancy tests may be conducted if required per local regulations). Postmenopausal&#xD;
             females (&gt; 45 years old and without menses for &gt; 1 year) and surgically sterilized&#xD;
             females are exempt from a pregnancy test&#xD;
&#xD;
         15. Male patients must agree to use an effective barrier method of contraception during&#xD;
             study and for 3 months following the last dose if sexually active with an FCBP&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Multiple myeloma of Immunoglobulin M (IgM) subtype&#xD;
&#xD;
          2. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and&#xD;
             skin changes)&#xD;
&#xD;
          3. Plasma cell leukemia (&gt; 2.0 × 10^9/L circulating plasma cells by standard&#xD;
             differential)&#xD;
&#xD;
          4. Waldenström's macroglobulinemia&#xD;
&#xD;
          5. Amyloidosis&#xD;
&#xD;
          6. Glucocorticoid therapy (prednisone &gt; 30 mg/day or equivalent) within 7 days prior to&#xD;
             enrollment&#xD;
&#xD;
          7. Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within&#xD;
             28 days prior to enrollment&#xD;
&#xD;
          8. Treatment with bortezomib (Velcade®), thalidomide (Thalomid®) or lenalidomide&#xD;
             (Revlimid®) within 21 days prior to enrollment&#xD;
&#xD;
          9. Focal radiation therapy within 7 days prior to enrollment. Radiation therapy to an&#xD;
             extended field involving a significant volume of bone marrow within 21 days prior to&#xD;
             enrollment (ie, prior radiation must have been to &lt; 30% of the bone marrow)&#xD;
&#xD;
         10. Immunotherapy within 21 days prior to enrollment&#xD;
&#xD;
         11. Major surgery within 21 days prior to enrollment&#xD;
&#xD;
         12. Active congestive heart failure (New York Heart Association [NYHA] Classes III to IV),&#xD;
             symptomatic ischemia, or conduction abnormalities uncontrolled by conventional&#xD;
             intervention. Myocardial infarction within 6 months prior to enrollment&#xD;
&#xD;
         13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral&#xD;
             therapy directed at hepatitis B virus [HBV]), or antifungal agents within 14 days&#xD;
             prior to enrollment&#xD;
&#xD;
         14. Known human immunodeficiency virus (HIV) seropositivity&#xD;
&#xD;
         15. Known hepatitis B or C virus infection (except for patients with HBV who are receiving&#xD;
             and responding to HBV antiviral therapy: these patients are allowed)&#xD;
&#xD;
         16. Patients with known cirrhosis&#xD;
&#xD;
         17. Second malignancy within the past 3 years, except:&#xD;
&#xD;
               1. Adequately treated basal cell or squamous cell skin cancer&#xD;
&#xD;
               2. Carcinoma in situ of the cervix&#xD;
&#xD;
               3. Prostate cancer &lt; Gleason score 6 with stable prostate-specific antigen (PSA)&#xD;
                  over 12 months&#xD;
&#xD;
               4. Breast carcinoma in situ with full surgical resection&#xD;
&#xD;
               5. Treated medullary or papillary thyroid cancer&#xD;
&#xD;
         18. Patients with myelodysplastic syndrome&#xD;
&#xD;
         19. Significant neuropathy (Grades 3 to 4) within 14 days prior to enrollment&#xD;
&#xD;
         20. Female patients who are pregnant or lactating&#xD;
&#xD;
         21. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize&#xD;
             carfilzomib)&#xD;
&#xD;
         22. Prior carfilzomib treatment&#xD;
&#xD;
         23. Prior participation in any Onyx-sponsored Phase 3 trial&#xD;
&#xD;
         24. Patients with contraindication to dexamethasone&#xD;
&#xD;
         25. Contraindication to any of the required concomitant drugs or supportive treatments,&#xD;
             including hypersensitivity to antiviral drugs, or intolerance to hydration due to&#xD;
             preexisting pulmonary or cardiac impairment&#xD;
&#xD;
         26. Ongoing graft-versus-host disease&#xD;
&#xD;
         27. Patients with pleural effusions requiring thoracentesis or ascites requiring&#xD;
             paracentesis within 14 days prior to enrollment&#xD;
&#xD;
         28. Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment&#xD;
&#xD;
         29. Any other clinically significant medical disease or psychiatric condition that, in the&#xD;
             Investigator's opinion, may interfere with protocol adherence or a patient's ability&#xD;
             to give informed consent&#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>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arizona Oncology Associates</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Blood and Cancer Center (CCBC)</name>
      <address>
        <city>Bakersfield</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Cancer Associates for Research and Excellence</name>
      <address>
        <city>Encinitas</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert A. Moss, M.D., FACP, Inc.</name>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Cancer Associates for Research and Excellence</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monterey Bay Oncology</name>
      <address>
        <city>Salinas</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sansum Clinic</name>
      <address>
        <city>Santa Barbara</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Coast Medical Oncology Corporation</name>
      <address>
        <city>Santa Maria</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James R. Berenson M.D. Inc.</name>
      <address>
        <city>West Hollywood</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Oncology Insititute of Hope and Innovation</name>
      <address>
        <city>Whittier</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - South</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - North</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Care</name>
      <address>
        <city>Galesburg</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Specialists</name>
      <address>
        <city>Hinsdale</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Illinois Cancer Specialists</name>
      <address>
        <city>Niles</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fort Wayne Oncology &amp; Hematology</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Horizon Oncology Research, Inc.</name>
      <address>
        <city>Lafayette</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Cancer and Blood Disorders (CCBD)</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematology-Oncology Associates of Northern NJ, PA</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Mexico Cancer Care Alliance</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Alliance</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hudson Valley Hematology Oncology Associates</name>
      <address>
        <city>Poughkeepsie</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Willamette Valley Cancer Institute and Research Center</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology, PLLC</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Joseph Regional Cancer Center</name>
      <address>
        <city>Bryan</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Millennium Oncology</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Waldron Medical Research and Development Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Care Centers of South Texas</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center at Cancer Therapy &amp; Research Center at The University of Texas Health Science Center at San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Blood and Cancer Center of East Texas</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shenandoah Oncology, PC</name>
      <address>
        <city>Winchester</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists</name>
      <address>
        <city>Vancouver</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yakima Valley Memorial Hospital/ North Star Lodge</name>
      <address>
        <city>Yakima</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Moreau P, Stewart KA, Dimopoulos M, Siegel D, Facon T, Berenson J, Raje N, Berdeja JG, Orlowski RZ, Yang H, Ma H, Klippel Z, Zahlten-Kumeli A, Mezzi K, Iskander K, Mateos MV. Once-weekly (70 mg/m2 ) vs twice-weekly (56 mg/m2 ) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.</citation>
    <PMID>32108443</PMID>
  </reference>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 31, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 3, 2012</study_first_posted>
  <results_first_submitted>July 11, 2017</results_first_submitted>
  <results_first_submitted_qc>July 11, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 9, 2017</results_first_posted>
  <last_update_submitted>September 12, 2022</last_update_submitted>
  <last_update_submitted_qc>September 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 23, 2022</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>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexamethasone</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at 32 centers in the United States. Participants were enrolled from September 2012 to September 2014.</recruitment_details>
      <pre_assignment_details>In phase 1 participants were enrolled into 1 of 4 sequential dose-escalating cohorts to establish the maximum tolerated dose (MTD) of carfilzomib plus dexamethasone. In phase 2 participants were enrolled to evaluate the efficacy and safety of carfilzomib plus dexamethasone at the MTD established in phase 1.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Phase 1: Carfilzomib 45 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="P2">
          <title>Phase 1: Carfilzomib 56 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="P3">
          <title>Phase 1: Carfilzomib 70 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="P4">
          <title>Phase 1: Carfilzomib 88 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="P5">
          <title>Phase 2: Carfilzomib 70 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</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="15"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="89"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0">Completed indicates participants ongoing in study</participants>
                <participants group_id="P2" count="1">Completed indicates participants ongoing in study</participants>
                <participants group_id="P3" count="1">Completed indicates participants ongoing in study</participants>
                <participants group_id="P4" count="0">Completed indicates participants ongoing in study</participants>
                <participants group_id="P5" count="4">Completed indicates participants ongoing in study</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="14"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="85"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="43"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="15"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</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_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Phase 1: Carfilzomib 45 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="B2">
          <title>Phase 1: Carfilzomib 56 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="B3">
          <title>Phase 1: Carfilzomib 70 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="B4">
          <title>Phase 1: Carfilzomib 88 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="B5">
          <title>Phase 2: Carfilzomib 70 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</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="15"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="89"/>
            <count group_id="B6" value="116"/>
          </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="69.3" spread="15.6"/>
                    <measurement group_id="B2" value="73.7" spread="2.1"/>
                    <measurement group_id="B3" value="62.4" spread="10.4"/>
                    <measurement group_id="B4" value="58.2" spread="8.8"/>
                    <measurement group_id="B5" value="68.7" spread="9.6"/>
                    <measurement group_id="B6" value="67.5" spread="10.1"/>
                  </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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="40"/>
                    <measurement group_id="B6" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="49"/>
                    <measurement group_id="B6" value="64"/>
                  </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="1"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="11"/>
                  </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="15"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="79"/>
                    <measurement group_id="B6" value="105"/>
                  </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/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="11"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="79"/>
                    <measurement group_id="B6" value="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="6"/>
                    <measurement group_id="B6" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <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="1"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaskan Native</title>
              <category_list>
                <category>
                  <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>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <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="1"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown</title>
              <category_list>
                <category>
                  <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="1"/>
                    <measurement group_id="B6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status</title>
          <description>Eastern Cooperative Oncology Group (ECOG) Performance Status is used by doctors and researchers to assess how a participants disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. 0 = Fully Active; 1 = Restricted activity but ambulatory; 2 = Ambulatory but unable to carry out work activities; 3 = Limited Self-Care; 4 = Completely Disabled, no self-care, confined to bed or chair; 5 = Dead.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0 (Fully active)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="39"/>
                    <measurement group_id="B6" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1 (Restrictive but ambulatory)</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="50"/>
                    <measurement group_id="B6" value="65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)</title>
        <description>The MTD was defined as the highest carfilzomib dose at which &lt; 33% of participants had a treatment-related DLT during the first 28-day cycle. A DLT was categorized as nonhematologic or hematologic and defined as follows:&#xD;
Nonhematologic:&#xD;
≥ grade 3 nonhematological toxicity (excluding nausea, vomiting, diarrhea, fatigue lasting &lt; 14 days, increased serum creatinine or electrolyte abnormalities not clinically significant or requiring treatment)&#xD;
≥ grade 3 acute kidney injury (creatinine &gt; 3 x baseline or &gt; 4.0 mg/dL) lasting &gt; 72 hours&#xD;
≥ grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy&#xD;
Hematologic:&#xD;
grade 4 neutropenia (absolute neutrophil count [ANC] &lt; 500/mm³) for &gt; 7 days&#xD;
febrile neutropenia (ANC &lt; 1000/mm³ with a fever ≥ 38.3ºC) of any duration&#xD;
grade 4 thrombocytopenia (&lt; 25 000/mm³) for &gt; 14 days, despite holding treatment&#xD;
grade 3 or 4 thrombocytopenia (&lt; lower limit of normal) associated with &gt; grade 1 bleeding</description>
        <time_frame>28 days</time_frame>
        <population>Participants in phase 1 who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1 Carfilzomib 45 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Carfilzomib 56 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Carfilzomib 88 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)</title>
          <description>The MTD was defined as the highest carfilzomib dose at which &lt; 33% of participants had a treatment-related DLT during the first 28-day cycle. A DLT was categorized as nonhematologic or hematologic and defined as follows:&#xD;
Nonhematologic:&#xD;
≥ grade 3 nonhematological toxicity (excluding nausea, vomiting, diarrhea, fatigue lasting &lt; 14 days, increased serum creatinine or electrolyte abnormalities not clinically significant or requiring treatment)&#xD;
≥ grade 3 acute kidney injury (creatinine &gt; 3 x baseline or &gt; 4.0 mg/dL) lasting &gt; 72 hours&#xD;
≥ grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy&#xD;
Hematologic:&#xD;
grade 4 neutropenia (absolute neutrophil count [ANC] &lt; 500/mm³) for &gt; 7 days&#xD;
febrile neutropenia (ANC &lt; 1000/mm³ with a fever ≥ 38.3ºC) of any duration&#xD;
grade 4 thrombocytopenia (&lt; 25 000/mm³) for &gt; 14 days, despite holding treatment&#xD;
grade 3 or 4 thrombocytopenia (&lt; lower limit of normal) associated with &gt; grade 1 bleeding</description>
          <population>Participants in phase 1 who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
          <units>participants</units>
          <param>Number</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="15"/>
                <count group_id="O4" value="6"/>
              </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="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Maximum Tolerated Dose (mg/m²)</param_type>
            <param_value>70</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Overall Response Rate (ORR)</title>
        <description>Disease response was evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). ORR was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).&#xD;
sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).&#xD;
CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and &lt; 5% plasma cells in BM.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein &lt;100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.&#xD;
PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to &lt; 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.</description>
        <time_frame>Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.</time_frame>
        <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Carfilzomib 45 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Carfilzomib 56 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Carfilzomib 88 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O5">
            <title>Phase 2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O6">
            <title>Phase 1+2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Response Rate (ORR)</title>
          <description>Disease response was evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). ORR was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).&#xD;
sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).&#xD;
CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and &lt; 5% plasma cells in BM.&#xD;
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein &lt;100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.&#xD;
PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to &lt; 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.</description>
          <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <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="15"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="89"/>
                <count group_id="O6" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3" lower_limit="0.8" upper_limit="90.6"/>
                    <measurement group_id="O2" value="100" lower_limit="29.2" upper_limit="100.0"/>
                    <measurement group_id="O3" value="93.3" lower_limit="68.1" upper_limit="99.8"/>
                    <measurement group_id="O4" value="66.7" lower_limit="22.3" upper_limit="95.7"/>
                    <measurement group_id="O5" value="74.2" lower_limit="63.8" upper_limit="82.9"/>
                    <measurement group_id="O6" value="76.9" lower_limit="67.6" upper_limit="84.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Response Rate</title>
        <description>Clinical benefit rate was defined as the percentage of participants whose best response was sCR, CR, VGPR, PR, or minimal response (MR), where MR is defined by the European Group for Blood and Marrow Transplant (EBMT) criteria as a 25% to 49% reduction in the level of serum M-protein or a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour, maintained for a minimum of 8 weeks.</description>
        <time_frame>Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.</time_frame>
        <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Carfilzomib 45 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Carfilzomib 56 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Carfilzomib 88 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O5">
            <title>Phase 2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O6">
            <title>Phase 1+2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Response Rate</title>
          <description>Clinical benefit rate was defined as the percentage of participants whose best response was sCR, CR, VGPR, PR, or minimal response (MR), where MR is defined by the European Group for Blood and Marrow Transplant (EBMT) criteria as a 25% to 49% reduction in the level of serum M-protein or a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour, maintained for a minimum of 8 weeks.</description>
          <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <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="15"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="89"/>
                <count group_id="O6" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.7" lower_limit="9.4" upper_limit="99.2"/>
                    <measurement group_id="O2" value="100.0" lower_limit="29.2" upper_limit="100.0"/>
                    <measurement group_id="O3" value="100.0" lower_limit="78.2" upper_limit="100.0"/>
                    <measurement group_id="O4" value="83.3" lower_limit="35.9" upper_limit="99.6"/>
                    <measurement group_id="O5" value="80.9" lower_limit="71.2" upper_limit="88.5"/>
                    <measurement group_id="O6" value="83.7" lower_limit="75.1" upper_limit="90.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival</title>
        <description>Progression-free survival (PFS) was defined as the time from first dose to the earlier of disease progression or death due to any cause. The duration of PFS was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.&#xD;
Participants were evaluated for disease response and progression by the investigator according to the IMWG-URC.</description>
        <time_frame>From randomization until the data cut-off date of 22 July 2016; median follow-up time for PFS was 13.8 months</time_frame>
        <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Carfilzomib 45 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Carfilzomib 56 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Carfilzomib 88 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O5">
            <title>Phase 2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O6">
            <title>Phase 1+2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival</title>
          <description>Progression-free survival (PFS) was defined as the time from first dose to the earlier of disease progression or death due to any cause. The duration of PFS was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.&#xD;
Participants were evaluated for disease response and progression by the investigator according to the IMWG-URC.</description>
          <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <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="15"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="89"/>
                <count group_id="O6" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.6" lower_limit="6.4" upper_limit="20.7"/>
                    <measurement group_id="O2" value="NA" lower_limit="41.7" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                    <measurement group_id="O3" value="21.0" lower_limit="4.2" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                    <measurement group_id="O4" value="12.9" lower_limit="3.9" upper_limit="20.0"/>
                    <measurement group_id="O5" value="15.3" lower_limit="10.0" upper_limit="20.2"/>
                    <measurement group_id="O6" value="16.2" lower_limit="10.2" upper_limit="21.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time To Progression</title>
        <description>Time to progression (TTP) was defined as the time from first dose to disease progression evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). TTP was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.</description>
        <time_frame>From randomization until the data cut-off date of 22 July 2016; median follow-up time for TTP was 13.4 months</time_frame>
        <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Carfilzomib 45 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Carfilzomib 56 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Carfilzomib 88 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O5">
            <title>Phase 2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O6">
            <title>Phase 1+2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Time To Progression</title>
          <description>Time to progression (TTP) was defined as the time from first dose to disease progression evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). TTP was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.</description>
          <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <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="15"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="89"/>
                <count group_id="O6" value="104"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.6" lower_limit="6.4" upper_limit="20.7"/>
                    <measurement group_id="O2" value="NA" lower_limit="41.7" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                    <measurement group_id="O3" value="21.0" lower_limit="4.2" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                    <measurement group_id="O4" value="12.9" lower_limit="3.9" upper_limit="20.0"/>
                    <measurement group_id="O5" value="16.2" lower_limit="10.2" upper_limit="20.2"/>
                    <measurement group_id="O6" value="17.2" lower_limit="10.6" upper_limit="21.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response</title>
        <description>Duration of response (DOR) was defined as the time from first evidence of PR or better to disease progression or death due to any cause. DOR was calculated using Kaplan-Meier methods; Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.</description>
        <time_frame>From randomization until the data cut-off date of 22 July 2016; median follow-up time for DOR was 14.3 months</time_frame>
        <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone) with a best overall response of sCR, CR, VGPR, or PR.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Carfilzomib 45 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Carfilzomib 56 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Carfilzomib 88 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O5">
            <title>Phase 2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O6">
            <title>Phase 1+2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response</title>
          <description>Duration of response (DOR) was defined as the time from first evidence of PR or better to disease progression or death due to any cause. DOR was calculated using Kaplan-Meier methods; Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.</description>
          <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone) with a best overall response of sCR, CR, VGPR, or PR.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="14"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="66"/>
                <count group_id="O6" value="80"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.9" lower_limit="NA" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="39.9" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                    <measurement group_id="O3" value="16.3" lower_limit="3.3" upper_limit="NA">Could not be estimated due to the low number of events</measurement>
                    <measurement group_id="O4" value="11.9" lower_limit="11.1" upper_limit="18.9"/>
                    <measurement group_id="O5" value="18.0" lower_limit="13.7" upper_limit="21.9"/>
                    <measurement group_id="O6" value="18.0" lower_limit="14.5" upper_limit="21.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Adverse events were graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (version 4.03).</description>
        <time_frame>From the first day of study treatment and within 30 days of the last day of study treatment; median duration of treatment was 33.6 weeks.</time_frame>
        <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 1: Carfilzomib 45 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O2">
            <title>Phase 1: Carfilzomib 56 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O3">
            <title>Phase 1: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O4">
            <title>Phase 1: Carfilzomib 88 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
          <group group_id="O5">
            <title>Phase 2: Carfilzomib 70 mg/m²</title>
            <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Adverse events were graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (version 4.03).</description>
          <population>Participants who received at least 1 dose of any investigational product (carfilzomib or dexamethasone).</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="15"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="89"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>All adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="15"/>
                    <measurement group_id="O4" value="6"/>
                    <measurement group_id="O5" value="89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adverse events ≥ grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="9"/>
                    <measurement group_id="O4" value="5"/>
                    <measurement group_id="O5" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="4"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE leading to discontinuation of carfilzomib &amp; dex</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AE leading to discontinuation of carfilzomib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Fatal adverse events</title>
              <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="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Plasma Concentration of Carfilzomib</title>
        <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib 20 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Carfilzomib 70 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
          <group group_id="O3">
            <title>Carfilzomib 88 mg/m²</title>
            <description>Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma Concentration of Carfilzomib</title>
          <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.25" lower_limit="0.17" upper_limit="0.75"/>
                    <measurement group_id="O2" value="0.25" lower_limit="0.08" upper_limit="0.58"/>
                    <measurement group_id="O3" value="0.25" lower_limit="0.25" upper_limit="0.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration of Carfilzomib</title>
        <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib 20 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Carfilzomib 70 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
          <group group_id="O3">
            <title>Carfilzomib 88 mg/m²</title>
            <description>Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration of Carfilzomib</title>
          <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="789" spread="65.5"/>
                    <measurement group_id="O2" value="2390" spread="30.7"/>
                    <measurement group_id="O3" value="3090" spread="27.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Carfilzomib</title>
        <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib 20 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Carfilzomib 70 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
          <group group_id="O3">
            <title>Carfilzomib 88 mg/m²</title>
            <description>Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Carfilzomib</title>
          <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
          <units>hr*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="281" spread="52.7"/>
                    <measurement group_id="O2" value="1040" spread="21.7"/>
                    <measurement group_id="O3" value="1210" spread="31.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) fo Carfilzomib</title>
        <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib 20 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Carfilzomib 70 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
          <group group_id="O3">
            <title>Carfilzomib 88 mg/m²</title>
            <description>Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) fo Carfilzomib</title>
          <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
          <units>hr*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="259" spread="28.0"/>
                    <measurement group_id="O2" value="1040" spread="21.6"/>
                    <measurement group_id="O3" value="1160" spread="34.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve During the Dosing Interval (0-168 Hours) for Carfilzomib</title>
        <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib 20 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Carfilzomib 70 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
          <group group_id="O3">
            <title>Carfilzomib 88 mg/m²</title>
            <description>Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve During the Dosing Interval (0-168 Hours) for Carfilzomib</title>
          <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
          <units>hr*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="259" spread="28.0"/>
                    <measurement group_id="O2" value="1040" spread="21.6"/>
                    <measurement group_id="O3" value="1160" spread="34.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Volume of Distribution Observed at Steady State (Vss) for Carfilzomib</title>
        <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib 20 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Carfilzomib 70 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
          <group group_id="O3">
            <title>Carfilzomib 88 mg/m²</title>
            <description>Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of Distribution Observed at Steady State (Vss) for Carfilzomib</title>
          <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
          <units>liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.0" spread="133.3"/>
                    <measurement group_id="O2" value="14.2" spread="54.2"/>
                    <measurement group_id="O3" value="7.87" spread="78.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-life (T1/2,z) for Carfilzomib</title>
        <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib 20 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Carfilzomib 70 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
          <group group_id="O3">
            <title>Carfilzomib 88 mg/m²</title>
            <description>Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-life (T1/2,z) for Carfilzomib</title>
          <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.648" spread="49"/>
                    <measurement group_id="O2" value="0.883" spread="24.6"/>
                    <measurement group_id="O3" value="0.816" spread="17.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clearance of Carfilzomib After IV Infusion</title>
        <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib 20 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Carfilzomib 70 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
          <group group_id="O3">
            <title>Carfilzomib 88 mg/m²</title>
            <description>Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
        </group_list>
        <measure>
          <title>Clearance of Carfilzomib After IV Infusion</title>
          <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
          <units>liters/hour</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="147" spread="31.0"/>
                    <measurement group_id="O2" value="131" spread="29.6"/>
                    <measurement group_id="O3" value="138" spread="35.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Residence Time Observed From Time Zero to Infinity (MRT0-∞) for Carfilzomib</title>
        <time_frame>Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.</time_frame>
        <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
        <group_list>
          <group group_id="O1">
            <title>Carfilzomib 20 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on day 1 cycle 1.</description>
          </group>
          <group group_id="O2">
            <title>Carfilzomib 70 mg/m²</title>
            <description>Participants in phase 1 and phase 2 received carfilzomib 70 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
          <group group_id="O3">
            <title>Carfilzomib 88 mg/m²</title>
            <description>Participants in phase 1 received carfilzomib 88 mg/m² administered by intravenous (IV) infusion from day 8 cycle 1 onwards.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Residence Time Observed From Time Zero to Infinity (MRT0-∞) for Carfilzomib</title>
          <population>Pharmacokinetic (PK) analyses were conducted for participants assigned to cohorts 3 and 4 in phase 1 (70 and 88 mg/m² carfilzomib) and a subset of participants in phase 2; only participants for whom PK parameters could be calculated were included in the analyses.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.118" spread="130.5"/>
                    <measurement group_id="O2" value="0.108" spread="55.4"/>
                    <measurement group_id="O3" value="0.0571" spread="110.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first day of study treatment and within 30 days of the last day of study treatment; median duration of treatment was 33.6 weeks.</time_frame>
      <desc>Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.</desc>
      <group_list>
        <group group_id="E1">
          <title>Phase 1: Carfilzomib 45 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 45 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="E2">
          <title>Phase 1: Carfilzomib 56 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 56 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="E3">
          <title>Phase 1: Carfilzomib 70 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="E4">
          <title>Phase 1: Carfilzomib 88 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 88 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
        <group group_id="E5">
          <title>Phase 2: Carfilzomib 70 mg/m²</title>
          <description>Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. The carfilzomib dose was 20 mg/m² on day 1 of cycle 1; thereafter, subsequent carfilzomib dosing was 70 mg/m². Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="35" subjects_at_risk="89"/>
              </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="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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Febrile 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Sinus 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Disease progression</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Pyrexia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Influenza</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Lung 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Pneumocystis jirovecii 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Pneumonia influenzal</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Septic shock</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Urinary tract 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Haematuria traumatic</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hip 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Lumbar vertebral 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcaemia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Metabolic acidosis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Musculoskeletal 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Acute lymphocytic leukaemia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Prostate cancer</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Aphasia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Encephalopathy</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hypertensive encephalopathy</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Syncope</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory distress syndrome</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary 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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hypoxia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Pneumonitis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Respiratory failure</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic dissection</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Deep vein thrombosis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="87" subjects_at_risk="89"/>
              </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="5" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="25" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="22" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Thrombocytosis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Arrhythmia</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>Porokeratosis</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Amblyopia</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Blindness</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Cataract</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Conjunctival 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dry eye</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Eye discharge</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Eye irritation</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Eye pruritus</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Glaucoma</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Periorbital 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Photophobia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Vision blurred</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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Visual acuity reduced</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Visual 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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Abdominal distension</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Abdominal 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Constipation</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="6" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="11" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Diarrhoea</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="9" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="26" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dyspepsia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Epigastric 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Flatulence</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Gastrointestinal tract irritation</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Gingival 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia oral</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Loose tooth</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="7" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="36" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Sensitivity of teeth</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Tooth loss</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Toothache</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="4" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="13" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</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="4" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Chest 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </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="4" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Cyst</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="47" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Feeling hot</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Influenza like illness</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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Malaise</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="4" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="4" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="20" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Peripheral 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Pyrexia</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="7" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="22" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Sluggishness</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Submandibular mass</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Cellulitis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Clostridium difficile 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Fungal skin 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Herpes zoster</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Influenza</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Joint abscess</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Localised 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Lung 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Mycobacterium avium complex 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</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="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Oral herpes</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Paronychia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Sinusitis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Tinea versicolour</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Tooth abscess</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Tooth 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</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="12" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="25" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Facial bones 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Foot 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>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="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Ligament sprain</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="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Post procedural complication</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase 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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase 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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="13" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Blood glucose 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Blood magnesium 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Blood potassium 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Blood sodium decreased</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Blood testosterone 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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Blood urea 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Cardiac murmur</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Haematocrit 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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Heart rate 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Neutrophil count 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="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Protein total 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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Urine output 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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Weight 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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>White blood cell count 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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="13" subjects_at_risk="89"/>
              </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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Fluid retention</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Iron deficiency</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Vitamin D deficiency</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="2" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="15" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Arthritis</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Back pain</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="5" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="18" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Groin 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="10" subjects_at_risk="89"/>
              </event>
              <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="5" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="12" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Musculoskeletal 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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="9" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Musculoskeletal discomfort</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Musculoskeletal 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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Myalgia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Myopathy</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Neck 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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Osteonecrosis of jaw</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="14" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Pain in jaw</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Benign neoplasm 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Melanocytic naevus</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Squamous 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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dizziness</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="5" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="14" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dizziness postural</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dysgeusia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Facial paralysis</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Headache</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="6" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="26" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Migraine</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Neuropathy 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="4" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Psychomotor hyperactivity</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Spinal cord compression</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Visual field defect</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Affective disorder</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Anger</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Anxiety</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="11" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Depression</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Insomnia</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="5" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="29" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Irritability</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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Mood altered</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Testicular 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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bradypnoea</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Cough</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="5" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="25" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dry throat</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dysphonia</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dyspnoea</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="5" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="25" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Epistaxis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Haemoptysis</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hiccups</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hypoxia</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </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="3" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Productive cough</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="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Pulmonary congestion</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Rhonchi</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Sinus congestion</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Sputum discoloured</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Throat irritation</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="89"/>
              </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="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </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="1" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Actinic keratosis</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Dermatitis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Ecchymosis</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Erythema</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hyperkeratosis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Night sweats</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Pruritus</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Pruritus generalised</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Rash</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="13" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Rash pruritic</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Skin lesion</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Swelling face</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Urticaria</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="15"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="89"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</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="2" subjects_at_risk="15"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="16" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Hypotension</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="89"/>
              </event>
              <event>
                <sub_title>Phlebitis</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="15"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="89"/>
              </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>The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Amgen Inc.</organization>
      <phone>866-572-6436</phone>
    </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/NCT01677858
org study id: 2012-002
secondary id: 20130403
nct id: NCT01677858
lead sponsor: 
has dmc: Yes
The study had the following primary objectives:

        -  Phase 1: to determine the maximum tolerated dose (MTD) of once-weekly (QW) carfilzomib
           and dexamethasone for patients with relapsed or refractory multiple myeloma who have
           received 1 to 3 prior therapies

        -  Phase 2: to estimate the overall response rate (ORR) for patients with relapsed or
           refractory multiple myeloma who received 1 to 3 prior therapies treated with carfilzomib
           and dexamethasone QW at the MTD established in phase 1.
This is a Phase 1/2, multicenter, single-arm, nonrandomized, open-label and dose-escalation
      study of weekly carfilzomib and dexamethasone for patients with progressive multiple myeloma.
      The Phase 1 dose escalation portion will enroll patients into sequential dose-escalating
      cohorts consisting of 3 patients each to establish the maximum tolerated dose (MTD) of
      carfilzomib administered weekly as a 30 minute intravenous (IV) infusion with dexamethasone.
      The Phase 2 portion will enroll patients using the MTD established for carfilzomib from the
      Phase 1 portion of the study. Dexamethasone will be administered IV or orally at the same
      dose and schedule as used in the Phase 1 portion of the study.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
time frame: 28 days
description: The MTD was defined as the highest carfilzomib dose at which < 33% of participants had a treatment-related DLT during the first 28-day cycle. A DLT was categorized as nonhematologic or hematologic and defined as follows:
Nonhematologic:
≥ grade 3 nonhematological toxicity (excluding nausea, vomiting, diarrhea, fatigue lasting < 14 days, increased serum creatinine or electrolyte abnormalities not clinically significant or requiring treatment)
≥ grade 3 acute kidney injury (creatinine > 3 x baseline or > 4.0 mg/dL) lasting > 72 hours
≥ grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy
Hematologic:
grade 4 neutropenia (absolute neutrophil count [ANC] < 500/mm³) for > 7 days
febrile neutropenia (ANC < 1000/mm³ with a fever ≥ 38.3ºC) of any duration
grade 4 thrombocytopenia (< 25 000/mm³) for > 14 days, despite holding treatment
grade 3 or 4 thrombocytopenia (< lower limit of normal) associated with > grade 1 bleeding
measure: Overall Response Rate (ORR)
time frame: Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.
description: Disease response was evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). ORR was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).
sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).
CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in BM.
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein <100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to < 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
measure: Clinical Benefit Response Rate
time frame: Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.
description: Clinical benefit rate was defined as the percentage of participants whose best response was sCR, CR, VGPR, PR, or minimal response (MR), where MR is defined by the European Group for Blood and Marrow Transplant (EBMT) criteria as a 25% to 49% reduction in the level of serum M-protein or a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour, maintained for a minimum of 8 weeks.
measure: Progression-free Survival
time frame: From randomization until the data cut-off date of 22 July 2016; median follow-up time for PFS was 13.8 months
description: Progression-free survival (PFS) was defined as the time from first dose to the earlier of disease progression or death due to any cause. The duration of PFS was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.
Participants were evaluated for disease response and progression by the investigator according to the IMWG-URC.
measure: Time To Progression
time frame: From randomization until the data cut-off date of 22 July 2016; median follow-up time for TTP was 13.4 months
description: Time to progression (TTP) was defined as the time from first dose to disease progression evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). TTP was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.
measure: Duration of Response
time frame: From randomization until the data cut-off date of 22 July 2016; median follow-up time for DOR was 14.3 months
description: Duration of response (DOR) was defined as the time from first evidence of PR or better to disease progression or death due to any cause. DOR was calculated using Kaplan-Meier methods; Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.
measure: Number of Participants With Adverse Events
time frame: From the first day of study treatment and within 30 days of the last day of study treatment; median duration of treatment was 33.6 weeks.
description: Adverse events were graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (version 4.03).
measure: Time to Maximum Plasma Concentration of Carfilzomib
time frame: Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
measure: Maximum Plasma Concentration of Carfilzomib
time frame: Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
measure: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Carfilzomib
time frame: Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
measure: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) fo Carfilzomib
time frame: Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
measure: Area Under the Plasma Concentration-time Curve During the Dosing Interval (0-168 Hours) for Carfilzomib
time frame: Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
measure: Volume of Distribution Observed at Steady State (Vss) for Carfilzomib
time frame: Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
measure: Terminal Half-life (T1/2,z) for Carfilzomib
time frame: Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
measure: Clearance of Carfilzomib After IV Infusion
time frame: Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
measure: Mean Residence Time Observed From Time Zero to Infinity (MRT0-∞) for Carfilzomib
time frame: Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
arm group label: Carfilzomib
arm group type: Experimental
description: In phase 1 participants were assigned to one of four sequential dose-escalating cohorts to receive 45, 56, 70 or 88 mg/m² carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
In phase 2 participants received carfilzomib at the maximum tolerated dose (MTD) established in the Phase 1 portion of the study on days 1, 8 and 15 plus 40 mg dexamethasone IV or orally at the same schedule as used in the Phase 1 portion of the study.
Participants were treated until confirmed progressive disease, unacceptable toxicity, withdrew consent for further treatment, were lost to follow-up, died, or the sponsor closed the study.
intervention type: Drug
intervention name: Carfilzomib
description: Carfilzomib was administered as a 30-minute IV infusion on days 1, 8, and 15 of each 28-day treatment cycle.
arm group label: Carfilzomib
other name: Krypolis
intervention type: Drug
intervention name: Dexamethasone
description: Dexamethasone was administered at a dose of 40 mg IV or orally (PO) on days 1, 8, 15, and 22 for the first 8 cycles; starting with cycle 9 dexamethasone was administered on days 1, 8, and 15.
arm group label: Carfilzomib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: MD
role: Study Director
affiliation: Amgen
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country: United States
citation: Moreau P, Stewart KA, Dimopoulos M, Siegel D, Facon T, Berenson J, Raje N, Berdeja JG, Orlowski RZ, Yang H, Ma H, Klippel Z, Zahlten-Kumeli A, Mezzi K, Iskander K, Mateos MV. Once-weekly (70 mg/m2 ) vs twice-weekly (56 mg/m2 ) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.
PMID: 32108443
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Dexamethasone
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 