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Phase 1/2 Safety and Efficacy of PLX3397 in Adults With Relapsed or Refractory Acute Myeloid Leukemia (AML)

Sponsor
Daiichi Sankyo, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01349049
Collaborator
Plexxikon (Industry)
90
Enrollment
9
Locations
9
Arms
73.6
Actual Duration (Months)
10
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety of study drug PLX3397 at 3 dose levels (800 mg/day, 1000 mg/day, and 1200 mg/day) and explore the efficacy in patients with relapsed or refractory acute myeloid leukemia (AML). Additional dose levels beyond 1200 mg/day may be considered based on safety and efficacy observations.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

Protocol PLX108-05 is a Phase 1/2 open-label, sequential dose escalation (Part 1) followed by cohort expansion (Part 2) design at the recommended phase 2 dose established in Part 1 (i.e. 3,000 mg/day). Treatment with PLX3397 will consist of continuous oral administration in 28-day cycles until unacceptable or dose-limiting toxicity, disease progression or relapse, patient death, Investigator decision, or voluntary withdrawal.

Study Design

Study Type:
Interventional
Actual Enrollment :
90 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Safety and Efficacy Study of Orally Administered PLX3397 in Adults With Relapsed or Refractory FLT3-ITD Positive Acute Myeloid Leukemia (AML)
Actual Study Start Date :
Nov 21, 2011
Actual Primary Completion Date :
Jan 20, 2015
Actual Study Completion Date :
Jan 9, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: oral dose of 3000 mg/day PLX3397 (RP2D)

Subjects will be dosed at the recommended Phase 2 dose (RP2D)

Drug: PLX3397
Maximum Tolerated Dose of PLX3397 will be administered orally, twice daily.
Other Names:
  • Plexxikon 3397

    		•
    Experimental: oral dose of 800 mg/day of PLX3397

    Level 0

    Drug: PLX3397
    The drug product is available in capsule form, to be taken orally.
    Other Names:
  • Plexxikon 3397

    		•
    Experimental: oral dose of 1000 mg/day PLX3397

    Level 1

    Drug: PLX3397
    The drug product is available in capsule form, to be taken orally.
    Other Names:
  • Plexxikon 3397

    		•
    Experimental: oral dose of 1200 mg/day PLX3397

    Level 2

    Drug: PLX3397
    The drug product is available in capsule form, to be taken orally.
    Other Names:
  • Plexxikon 3397

    		•
    Experimental: oral dose of 1400 mg/day PLX3397

    Level 3

    Drug: PLX3397
    The drug product is available in capsule form, to be taken orally.
    Other Names:
  • Plexxikon 3397

    		•
    Experimental: oral dose of 2000 mg/day PLX3397

    Level 4

    Drug: PLX3397
    The drug product is available in capsule form, to be taken orally.
    Other Names:
  • Plexxikon 3397

    		•
    Experimental: oral dose of 3000 mg/day PLX3397

    Level 5

    Drug: PLX3397
    The drug product is available in capsule form, to be taken orally.
    Other Names:
  • Plexxikon 3397

    		•
    Experimental: oral dose of 4000 mg/day PLX3397

    Level 6

    Drug: PLX3397
    The drug product is available in capsule form, to be taken orally.
    Other Names:
  • Plexxikon 3397

    		•
    Experimental: oral dose of 5000 mg/day PLX3397

    Level 7

    Drug: PLX3397
    The drug product is available in capsule form, to be taken orally.
    Other Names:
  • Plexxikon 3397

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Summary of Best Modified Criteria Response Results, Bridged-to-Transplant (BTT) Participants, and Composite Remission Rates in Patients on Treatment With PLX3397 (Dose Expansion, Part 2). [1 year post dose]

      Complete remission (CR): Has bone marrow regenerating normal cells, achieve a morphologic leukemia-free state, Complete remission with incomplete platelet recovery (CRp): CR except for incomplete platelet recovery, Complete remission with incomplete recovery (CRi): CR except for incomplete hematological recovery with residual neutropenia, Partial response (PR): bone marrow generates normal hematopoietic cells, evidence of peripheral recovery with no or a few regenerating circulating blasts. Decrease of ≥50% of blasts in bone marrow aspirate, total marrow blasts between 5% -25%, Non-response (NR) were assessed using modified International Working Group (IWG) response criteria for AML. Successfully (BTT) patients and successfully BTT patients (CR, CRp, or CRi) are also reported. Successfully BTT is defined as any patient who discontinued PLX3397 treatment specifically for the purpose of undergoing a hematopoietic stem cell transplant and who subsequently received the planned transplant.

    2. Summary of Time-to-Event Endpoints in Patients on Treatment With PLX3397 (Dose Expansion, Part 2) [1 year post dose]

      Median survival estimates were based on the Kaplan-Meier method. In the event disease progression/relapse or death was not documented prior to study termination, endpoints were censored at the date of last evaluable tumor assessment. Duration of remission, duration of complete remission, and disease-free survival, initial response was based on the modified response criteria. Duration of complete remission was defined as the number of days from the date of initial CR, CRp, or CRi response to the date of first documented disease relapse or death, whichever occurred first. Disease-free survival was defined as the number of days from the date of initial CR, CRp, or CRi to the date of documented disease relapse or death from any cause, whichever occurred first.

    Secondary Outcome Measures

    1. Number of Participants With On-treatment Best Modified Criteria Response Results of Partial Remission (PR) During Treatment With PLX3397 (Dose Expansion, Part 2) [1 year post dose]

      Modified International Working Group Response Criteria for Acute Myeloid Leukemia defines Partial Remission (PR) as the following: Partial Remission (PR): Patients must have bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts and with a decrease of at least 50% in the percentage of blasts in the bone marrow aspirate with the total marrow blasts between 5% and 25%. In addition, patients do not need to be Red Blood Cell (RBC) or platelet transfusion independent.

    2. Number of Participants With On-treatment Best Classic Criteria Response Results During Treatment With PLX3397 (Dose Expansion, Part 2) [1 year post dose]

      Complete Remission (CR): Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1000/μL); platelet count >100 x 109/L (100000/μL); red cell transfusion independent CR with incomplete recovery (CRi): All CR criteria except for residual neutropenia (<1.0 x 109/L) or thrombocytopenia Partial Remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5-25%; decrease of pretreatment bone marrow blast percentage by at least 50%.

    3. Number of Participants Reporting an Incidence of Adverse Events During Treatment With PLX3397 (Part 1, Dose Escalation and Part 2, Dose Expansion) [1 year post dose]

    4. Number of Participants Reporting an Incidence of Treatment-Related Treatment Emergent Adverse Events During Treatment With PLX3397 (Dose Escalation, Part 1 and Dose Expansion, Part 2) [1 year post dose]

      Data reported are Treatment-Related Treatment Emergent Adverse Events that are ≥15% Occurrence in all patients.

    5. Number of Participants Reporting a Treatment Emergent Adverse Events With a CTCAE Grade ≥3 During Treatment With PLX3397 (Dose Escalation, Part 1 and Dose Expansion, Part 2) [1 year post dose]

      Data reported are Treatment Emergent Adverse Events with a CTCAE Grade ≥3 During Treatment that are ≥10% Occurrence in all patients.

    6. Number of Participants With Clinically Significant Abnormal Chemistry and Hematology Values Reported as Adverse Events (AE) During Treatment With PLX3397 (Dose Escalation, Part 1 and Dose Expansion, Part 2) [1 year post dose]

    Other Outcome Measures

    1. A Summary of Time From Initial Dosing to First and Best Response, Modified Response Criteria in Patient Treated With PLX3397 (Dose Expansion, Part 2) [1 year post dose]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Male or female patients ≥18 years old.

    • Morphologically documented primary Acute Myeloid Leukemia (AML), prior-chemotherapy-related AML or AML secondary to an antecedent hematologic disorder (e.g., Myelodysplastic Syndrome) as defined by World Health Organization criteria, confirmed by pathology review. For Cohort Expansion Phase (Part 2) only: Bone marrow involvement is required.

    • Have either relapsed or refractory AML, or who have newly diagnosed Flt3-ITD positive AML but either refuse or are considered by the Investigator not to be an appropriate candidate for standard chemotherapy.

    1. Relapsed disease is defined as the reappearance of leukemia cells in the bone marrow or peripheral blood or elsewhere in the body (other tissues/organs) after the attainment of a CR.

    2. Refractory disease is defined by the failure to obtain a complete remission (CR) with a High-Dose Cytarabine (HDAC)-containing or a standard induction regimen. Patients who require two cycles of induction therapy to attain a first CR are not considered to have refractory disease.

    • Positive for Flt3-ITD activating mutations during Screening. Local laboratory results must be received prior to enrollment. Patients with a history of Flt3-ITD positive disease may be considered after discussion with the Medical Monitor.

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.

    • Adequate recovery (to at least Grade 1) from toxicity of prior therapy as follows:

    1. ≥2 weeks for cytotoxic therapy (except hydroxyurea, which is permitted at doses of ≤5g/day during the first 2 weeks of Cycle 1) prior to C1D1.

    2. ≥4 half-lives for non-cytotoxic therapy prior to C1D1. Patients must have a wash-out period from their last chemotherapy of either ≥2 weeks OR at least 4 half-lives prior to C1D1. For patients whose most recent anti-tumor treatment regimen consisted of a multi-agent cocktail, the patient must have a wash-out period of at least 4 half-lives of the agent with the longest half-life.

    • Adequate hepatic and renal function

    1. Adequate renal function, defined as Creatinine Clearance >60 mL/min or serum creatinine of ≤ 1.3 mg/dL (115 μM).

    2. Adequate hepatic function, defined as Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤3.0X Upper limit of normal (ULN) and serum direct bilirubin ≤1.5X ULN. Exceptions may be made for patients with elevated liver transaminases secondary to AML after discussion with the Medical Monitor

    • Life expectancy of at least 1 month

    • Willing and able to provide written informed consent prior to any study related procedures and to comply with all study requirements and for 3 months after last dose.

    • Women of child-bearing potential must have a negative pregnancy test within 7 days of initiation of dosing and must agree to use two acceptable methods of birth control while on study drug and for 3 months after the last dose. Women of non-childbearing potential may be included if they meet at least one of the following criteria:

    1. Surgically sterile

    2. Have been postmenopausal for ≥1 year

    3. Have Follicle Stimulating Hormone (FSH) levels indicative of postmenopausal state (i.e., 30-120 IU/L) documented within 21 days of C1D1.

    Sexually active men must also agree to use an acceptable method of birth control while on study drug and for at least 3 months after the last dose

    Exclusion Criteria:

    • Diagnosis of acute promyelocytic leukemia

    • Diagnosis of chronic myelogenous leukemia in blast crisis

    • Presence of central nervous system (CNS) involvement of leukemia. Patients with a history of CNS involvement may be considered after discussion with the Medical Monitor

    • Patients eligible for Hematopoietic Stem Cell Transplantation (HSCT) at the time of screening. However, patients who meet one or both of the following criteria may be eligible for study participation:

    1. Patients who are eligible for HSCT but with non-optimal AML disease control (i.e., blasts > 5%) may be enrolled into this study as a bridge-to-transplant.

    2. Patients with relapsed disease following a prior HSCT may be enrolled into this study as an alternative to a second HSCT or as a bridge-to-transplant regimen.

    • For both Parts 1 and 2, receipt of HSCT within 60 days of the first dose of PLX3397 is an exclusion criterion. Patients on immunosuppressive therapy post HSCT, or with clinically significant graft-versus-host disease are excluded from Part 1. (Use of topical steroids for ongoing skin Graft vs. host disease [GVHD] is permitted). Patients for Part 1 must have a wash-out period of ≥2 weeks or at least 4 half-lives from their last systemic immunosuppressive treatment for Graft vs. host disease. Patients for Part 2 may be receiving systemic immunosuppressive treatment for management of GVHD at the time of screening and enrollment

    • Investigational drug use within 28 days of the first dose of PLX3397

    • For Cohort Expansion Phase (Part 2) only: Patients who are positive for the D835 mutation at Screening are excluded.

    • A concurrent active cancer that requires non-surgical therapy (e.g., chemotherapy, radiation, adjuvant therapy). Prior history of other cancer is allowed, as long as there is no active disease within 1 year of the first dose of PLX3397.

    • Refractory nausea and vomiting, malabsorption, biliary shunt significant bowel resection, GVHD affecting the gut, or any other condition that would preclude adequate absorption

    • Patients with serious illnesses, uncontrolled infection, medical conditions, or other medical history including abnormal laboratory results, which in the investigator's opinion would be likely to interfere with a patient's participation in the study, or with the interpretation of the results

    • Women of child-bearing potential who are pregnant or breast feeding

    • At Screening, QT interval, Frederica's formula (QTcF) >450 msec for males; QTcF >470 msec for females

    • Patients with a history of D835 mutations

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 UCSF Helen Diller Family Family Comprehensive Cancer Center San Francisco California United States 94143
    2 Northwestern University Chicago Illinois United States 60611
    3 Johns Hopkins University Baltimore Maryland United States 21231
    4 Dana Farber Cancer Institute Boston Massachusetts United States 02215
    5 Roswell Park Cancer Institute Buffalo New York United States 14263
    6 Memorial Sloan Kettering Cancer Center New York New York United States 10022
    7 New York Presby Hospital, Weill Medical College at Cornell University New York New York United States 10065
    8 University of Pennsylvania, Abramson Cancer Center Philadelphia Pennsylvania United States 19104
    9 Fred Hutchinson Cancer Research Center Seattle Washington United States 98109

    Sponsors and Collaborators

    • Daiichi Sankyo, Inc.
    • Plexxikon

    Investigators

    • Principal Investigator: Olga Frankfurt, MD, Robert H. Lurie Comprehensive Cancer Center of Northwestern University - Chicago, IL
    • Principal Investigator: Mark Levis, MD, PhD, Johns Hopkins University
    • Principal Investigator: John Pagel, MD, PhD, Fred Hutchinson Cancer Research Center - Seattle, WA
    • Principal Investigator: Alexander Perl, MD, Hospital of the University of Pennsylvania - Philadelphia, PA
    • Principal Investigator: Gail Roboz, MD, Weill Cornell Medical College/New York Presbyterian Hospital - New York, NY
    • Principal Investigator: Catherine Smith, MD, University of California Medical Center - San Francisco, CA
    • Principal Investigator: Richard Stone, MD, Dana-Farber Cancer Institute - Boston, MA
    • Principal Investigator: Eunice Wang, MD, Roswell Park Cancer Institute - Buffalo, NY

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Daiichi Sankyo, Inc.
    ClinicalTrials.gov Identifier:
    NCT01349049
    Other Study ID Numbers:
    • PLX108-05
    First Posted:
    May 6, 2011
    Last Update Posted:
    Mar 2, 2020
    Last Verified:
    Feb 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Daiichi Sankyo, Inc.
    AML
    relapsed
    refractory
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute

    Study Results

    Participant Flow

    Recruitment Details A total of 90 participants (34 in Part 1 and 56 in part 2) were enrolled in the study and received PLX3397.
    Pre-assignment Detail The study participants enrolled are patients with relapsed or refractory Flt3-ITD+ AML, or newly diagnosed Flt3-ITD + AML patients who either refused or were considered not to be appropriate candidates for chemotherapy.
    Arm/Group Title Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 800 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1200 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1400 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 2000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 4000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 5000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day.
    Period Title: Overall Study
    STARTED 3 7 3 3 3 6 5 4 56
    COMPLETED 0 0 0 0 0 0 0 0 1
    NOT COMPLETED 3 7 3 3 3 6 5 4 55

    Baseline Characteristics

    Arm/Group Title Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day Total
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 800 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1200 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1400 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 2000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 4000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 5000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day Total of all reporting groups
    Overall Participants 3 7 3 3 3 6 5 4 56 90
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    58.0
    (28.2)
    56.7
    (18.5)
    65.7
    (12.9)
    61.7
    (19.7)
    70.7
    (11.2)
    61.0
    (9.7)
    54.8
    (14.5)
    63.8
    (2.5)
    55.9
    (14.6)
    57.7
    (14.72)
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    5
    71.4%
    2
    66.7%
    2
    66.7%
    1
    33.3%
    4
    66.7%
    4
    80%
    3
    75%
    23
    41.1%
    44
    48.9%
    Male
    3
    100%
    2
    28.6%
    1
    33.3%
    1
    33.3%
    2
    66.7%
    2
    33.3%
    1
    20%
    1
    25%
    33
    58.9%
    46
    51.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.1%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    3
    5.4%
    4
    4.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    4
    57.1%
    1
    33.3%
    0
    0%
    0
    0%
    1
    16.7%
    1
    20%
    0
    0%
    7
    12.5%
    14
    15.6%
    White
    2
    66.7%
    2
    28.6%
    2
    66.7%
    2
    66.7%
    3
    100%
    5
    83.3%
    3
    60%
    2
    50%
    35
    62.5%
    56
    62.2%
    More than one race
    0
    0%
    1
    14.3%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    20%
    1
    25%
    11
    19.6%
    15
    16.7%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    3
    100%
    7
    100%
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    5
    100%
    4
    100%
    56
    100%
    90
    100%

    Outcome Measures

    1. Primary Outcome
    Title Summary of Best Modified Criteria Response Results, Bridged-to-Transplant (BTT) Participants, and Composite Remission Rates in Patients on Treatment With PLX3397 (Dose Expansion, Part 2).
    Description Complete remission (CR): Has bone marrow regenerating normal cells, achieve a morphologic leukemia-free state, Complete remission with incomplete platelet recovery (CRp): CR except for incomplete platelet recovery, Complete remission with incomplete recovery (CRi): CR except for incomplete hematological recovery with residual neutropenia, Partial response (PR): bone marrow generates normal hematopoietic cells, evidence of peripheral recovery with no or a few regenerating circulating blasts. Decrease of ≥50% of blasts in bone marrow aspirate, total marrow blasts between 5% -25%, Non-response (NR) were assessed using modified International Working Group (IWG) response criteria for AML. Successfully (BTT) patients and successfully BTT patients (CR, CRp, or CRi) are also reported. Successfully BTT is defined as any patient who discontinued PLX3397 treatment specifically for the purpose of undergoing a hematopoietic stem cell transplant and who subsequently received the planned transplant.
    Time Frame 1 year post dose

    Outcome Measure Data

    Analysis Population Description
    Efficacy analyses were conducted in the Part 2 Efficacy Population.
    Arm/Group Title Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day.
    Measure Participants 56
    CR
    1
    33.3%
    CRp
    1
    33.3%
    CRi
    4
    133.3%
    PR
    5
    166.7%
    NR
    45
    1500%
    Successful BTT patients
    4
    133.3%
    Successful BTT patient (CR, CRp, or CRi)
    8
    266.7%
    2. Primary Outcome
    Title Summary of Time-to-Event Endpoints in Patients on Treatment With PLX3397 (Dose Expansion, Part 2)
    Description Median survival estimates were based on the Kaplan-Meier method. In the event disease progression/relapse or death was not documented prior to study termination, endpoints were censored at the date of last evaluable tumor assessment. Duration of remission, duration of complete remission, and disease-free survival, initial response was based on the modified response criteria. Duration of complete remission was defined as the number of days from the date of initial CR, CRp, or CRi response to the date of first documented disease relapse or death, whichever occurred first. Disease-free survival was defined as the number of days from the date of initial CR, CRp, or CRi to the date of documented disease relapse or death from any cause, whichever occurred first.
    Time Frame 1 year post dose

    Outcome Measure Data

    Analysis Population Description
    Time-to-event analyses were assessed in the Part 2 Efficacy Population.
    Arm/Group Title Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day.
    Measure Participants 56
    Duration of remission
    91
    Duration of complete remission
    289
    Progression-free survival
    48
    Disease-free survival
    289
    Overall survival
    112
    3. Secondary Outcome
    Title Number of Participants With On-treatment Best Modified Criteria Response Results of Partial Remission (PR) During Treatment With PLX3397 (Dose Expansion, Part 2)
    Description Modified International Working Group Response Criteria for Acute Myeloid Leukemia defines Partial Remission (PR) as the following: Partial Remission (PR): Patients must have bone marrow regenerating normal hematopoietic cells with evidence of peripheral recovery with no (or only a few regenerating) circulating blasts and with a decrease of at least 50% in the percentage of blasts in the bone marrow aspirate with the total marrow blasts between 5% and 25%. In addition, patients do not need to be Red Blood Cell (RBC) or platelet transfusion independent.
    Time Frame 1 year post dose

    Outcome Measure Data

    Analysis Population Description
    Efficacy analyses were conducted in the Part 2 Efficacy Population.
    Arm/Group Title Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day
    Measure Participants 56
    Count of Participants [Participants]
    5
    166.7%
    4. Secondary Outcome
    Title Number of Participants With On-treatment Best Classic Criteria Response Results During Treatment With PLX3397 (Dose Expansion, Part 2)
    Description Complete Remission (CR): Bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count >1.0 x 109/L (1000/μL); platelet count >100 x 109/L (100000/μL); red cell transfusion independent CR with incomplete recovery (CRi): All CR criteria except for residual neutropenia (<1.0 x 109/L) or thrombocytopenia Partial Remission (PR): All hematologic criteria of CR; decrease of bone marrow blast percentage to 5-25%; decrease of pretreatment bone marrow blast percentage by at least 50%.
    Time Frame 1 year post dose

    Outcome Measure Data

    Analysis Population Description
    Efficacy analyses were conducted in the Part 2 Efficacy Population.
    Arm/Group Title Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day.
    Measure Participants 56
    CR
    2
    66.7%
    CRi
    6
    200%
    PR
    2
    66.7%
    NR
    46
    1533.3%
    5. Secondary Outcome
    Title Number of Participants Reporting an Incidence of Adverse Events During Treatment With PLX3397 (Part 1, Dose Escalation and Part 2, Dose Expansion)
    Description
    Time Frame 1 year post dose

    Outcome Measure Data

    Analysis Population Description
    Adverse events were assessed in the Safety Population.
    Arm/Group Title Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 800 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1200 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1400 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 2000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 4000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 5000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day.
    Measure Participants 3 7 3 3 3 6 5 4 56
    At least 1 AE
    3
    100%
    7
    100%
    3
    100%
    3
    100%
    3
    100%
    6
    100%
    5
    100%
    4
    100%
    56
    100%
    At least 1 treatment-related AE
    2
    66.7%
    4
    57.1%
    3
    100%
    3
    100%
    3
    100%
    4
    66.7%
    4
    80%
    4
    100%
    49
    87.5%
    AE that lead to change in drug administration
    0
    0%
    4
    57.1%
    2
    66.7%
    1
    33.3%
    2
    66.7%
    5
    83.3%
    4
    80%
    3
    75%
    28
    50%
    At least 1 AE with CTCAE Grade >=3
    3
    100%
    7
    100%
    2
    66.7%
    3
    100%
    2
    66.7%
    5
    83.3%
    5
    100%
    4
    100%
    50
    89.3%
    Serious Adverse Event (SAE)or other significant AE
    1
    33.3%
    5
    71.4%
    2
    66.7%
    1
    33.3%
    2
    66.7%
    5
    83.3%
    4
    80%
    4
    100%
    39
    69.6%
    At least 1 treatment-related Serious Adverse Event
    0
    0%
    2
    28.6%
    0
    0%
    1
    33.3%
    1
    33.3%
    1
    16.7%
    0
    0%
    1
    25%
    10
    17.9%
    AE resulting in death
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    50%
    0
    0%
    0
    0%
    9
    16.1%
    SAE leading to discontinuation of study drug
    0
    0%
    2
    28.6%
    0
    0%
    0
    0%
    0
    0%
    3
    50%
    2
    40%
    0
    0%
    9
    16.1%
    6. Secondary Outcome
    Title Number of Participants Reporting an Incidence of Treatment-Related Treatment Emergent Adverse Events During Treatment With PLX3397 (Dose Escalation, Part 1 and Dose Expansion, Part 2)
    Description Data reported are Treatment-Related Treatment Emergent Adverse Events that are ≥15% Occurrence in all patients.
    Time Frame 1 year post dose

    Outcome Measure Data

    Analysis Population Description
    Adverse events were assessed in the Safety Population.
    Arm/Group Title Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 800 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1200 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1400 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 2000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 4000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 5000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day
    Measure Participants 3 7 3 3 3 6 5 4 56
    At least 1 treatment-related AE
    2
    66.7%
    4
    57.1%
    3
    100%
    3
    100%
    3
    100%
    4
    66.7%
    4
    80%
    4
    100%
    49
    87.5%
    Nausea
    2
    66.7%
    1
    14.3%
    2
    66.7%
    3
    100%
    0
    0%
    2
    33.3%
    1
    20%
    3
    75%
    21
    37.5%
    Diarrhoea
    1
    33.3%
    1
    14.3%
    1
    33.3%
    1
    33.3%
    1
    33.3%
    0
    0%
    3
    60%
    1
    25%
    19
    33.9%
    Vomiting
    0
    0%
    2
    28.6%
    1
    33.3%
    2
    66.7%
    0
    0%
    2
    33.3%
    1
    20%
    3
    75%
    15
    26.8%
    Fatigue
    0
    0%
    1
    14.3%
    1
    33.3%
    1
    33.3%
    1
    33.3%
    2
    33.3%
    1
    20%
    2
    50%
    18
    32.1%
    Decreased appetite
    1
    33.3%
    0
    0%
    0
    0%
    1
    33.3%
    1
    33.3%
    2
    33.3%
    1
    20%
    1
    25%
    16
    28.6%
    Anaemia
    0
    0%
    1
    14.3%
    1
    33.3%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    2
    50%
    9
    16.1%
    Aspartate aminotransferase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    1
    16.7%
    1
    20%
    1
    25%
    10
    17.9%
    Dysgeusia
    0
    0%
    1
    14.3%
    0
    0%
    2
    66.7%
    2
    66.7%
    2
    33.3%
    0
    0%
    2
    50%
    6
    10.7%
    7. Secondary Outcome
    Title Number of Participants Reporting a Treatment Emergent Adverse Events With a CTCAE Grade ≥3 During Treatment With PLX3397 (Dose Escalation, Part 1 and Dose Expansion, Part 2)
    Description Data reported are Treatment Emergent Adverse Events with a CTCAE Grade ≥3 During Treatment that are ≥10% Occurrence in all patients.
    Time Frame 1 year post dose

    Outcome Measure Data

    Analysis Population Description
    Adverse events were assessed in the Safety Population.
    Arm/Group Title Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 800 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1200 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1400 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 2000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 4000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 5000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day
    Measure Participants 3 7 3 3 3 6 5 4 56
    At least 1 AE with CTCAE Grade ≥3
    3
    100%
    7
    100%
    2
    66.7%
    3
    100%
    2
    66.7%
    5
    83.3%
    5
    100%
    4
    100%
    50
    89.3%
    Febrile neutropenia
    1
    33.3%
    5
    71.4%
    1
    33.3%
    3
    100%
    1
    33.3%
    1
    16.7%
    2
    40%
    2
    50%
    22
    39.3%
    Anaemia
    0
    0%
    1
    14.3%
    0
    0%
    1
    33.3%
    1
    33.3%
    0
    0%
    2
    40%
    1
    25%
    9
    16.1%
    Thrombocytopenia
    0
    0%
    1
    14.3%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    3
    75%
    7
    12.5%
    Sepsis
    0
    0%
    0
    0%
    1
    33.3%
    1
    33.3%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    10
    17.9%
    Platelet count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    20%
    0
    0%
    10
    17.9%
    Fatigue
    2
    66.7%
    0
    0%
    0
    0%
    1
    33.3%
    1
    33.3%
    1
    16.7%
    0
    0%
    1
    25%
    3
    5.4%
    8. Secondary Outcome
    Title Number of Participants With Clinically Significant Abnormal Chemistry and Hematology Values Reported as Adverse Events (AE) During Treatment With PLX3397 (Dose Escalation, Part 1 and Dose Expansion, Part 2)
    Description
    Time Frame 1 year post dose

    Outcome Measure Data

    Analysis Population Description
    Adverse events were assessed in the Safety Population.
    Arm/Group Title Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 800 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1200 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1400 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 2000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day Participants with relapsed or refractory acute myeloid leukemia (AML) who received PLX3397 4000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 5000 mg/day Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day
    Measure Participants 3 7 3 3 3 6 5 4 56
    Anaemia
    0
    0%
    1
    14.3%
    1
    33.3%
    1
    33.3%
    1
    33.3%
    0
    0%
    2
    40%
    3
    75%
    15
    26.8%
    Hypokalaemia
    1
    33.3%
    0
    0%
    1
    33.3%
    2
    66.7%
    0
    0%
    1
    16.7%
    2
    40%
    2
    50%
    13
    23.2%
    Aspartate aminotransferase increased
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    2
    66.7%
    1
    16.7%
    1
    20%
    1
    25%
    13
    23.2%
    Thrombocytopenia
    0
    0%
    1
    14.3%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    20%
    3
    75%
    9
    16.1%
    Hypomagnesmia
    1
    33.3%
    0
    0%
    1
    33.3%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    2
    50%
    10
    17.9%
    Hypocalcaemia
    1
    33.3%
    1
    14.3%
    0
    0%
    0
    0%
    1
    33.3%
    1
    16.7%
    1
    20%
    1
    25%
    8
    14.3%
    Platelet count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    20%
    0
    0%
    12
    21.4%
    Blood alkaline phosphatase increase
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    20%
    1
    25%
    10
    17.9%
    Hyperglycaemia
    0
    0%
    2
    28.6%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    1
    25%
    9
    16.1%
    Hyponatraemia
    0
    0%
    2
    28.6%
    0
    0%
    0
    0%
    1
    33.3%
    2
    33.3%
    0
    0%
    1
    25%
    5
    8.9%
    Alanine aminotransferase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    1
    16.7%
    1
    20%
    1
    25%
    6
    10.7%
    Blood bilirubin increased
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    7
    12.5%
    Hypoalbuminaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    8
    14.3%
    Hypophosphataemia
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    7
    12.5%
    Transaminases increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    20%
    1
    25%
    5
    8.9%
    White blood cell count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    7
    12.5%
    Neutropenia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    2
    50%
    4
    7.1%
    Lymphocyte count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    7
    12.5%
    Neutrophil count decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    6
    10.7%
    Leukocytosis
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    2
    3.6%
    Blood cholesterol increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    5.4%
    Hyperbilirubinaemia
    1
    33.3%
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Hyperuricaemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    3
    5.4%
    Activated partial thromboplastin time prolonged
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    3.6%
    Blood urea decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    3.6%
    Blood uric acid increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    50%
    0
    0%
    Leukopenia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    3.6%
    Hyperchloraemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    3.6%
    Hyperkalaemia
    1
    33.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Bilirubin conjugated increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Blast cell count increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Blood albumin decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Blood chloride increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Blood creatinine phosphokinase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Blood fibrinogen decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Carbon monoxide diffusing capacity decreased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Gamma glutamyl transferase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Globulins increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    INR increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    Lipase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Myeloblast count increased
    0
    0%
    1
    14.3%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Troponin increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    White blood cell count increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    25%
    0
    0%
    Hypernatraemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    1.8%
    Hyperphosphataemia
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    9. Other Pre-specified Outcome
    Title A Summary of Time From Initial Dosing to First and Best Response, Modified Response Criteria in Patient Treated With PLX3397 (Dose Expansion, Part 2)
    Description
    Time Frame 1 year post dose

    Outcome Measure Data

    Analysis Population Description
    Efficacy analyses were assessed in Part 2 Efficacy Population
    Arm/Group Title Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day
    Measure Participants 11
    Time to First Response
    29
    Time to Best Response
    30

    Adverse Events

    Time Frame Adverse event data were collected from after the first dose to 30 days after the last dose.
    Adverse Event Reporting Description Adverse events that emerge (or worsen) after the first dose of study drug and within 30 days after the last dose.
    Arm/Group Title Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day
    Arm/Group Description Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 800 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1200 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 1400 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 2000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 4000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 5000 mg/day. Participants with acute myeloid leukemia (AML), either relapsed/refractory or newly diagnosed and unfit to receive chemotherapy, received PLX3397 3000 mg/day.
    All Cause Mortality
    Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 5/56 (8.9%)
    Serious Adverse Events
    Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/3 (33.3%) 5/7 (71.4%) 2/3 (66.7%) 1/3 (33.3%) 2/3 (66.7%) 5/6 (83.3%) 4/5 (80%) 4/4 (100%) 39/56 (69.6%)
    Blood and lymphatic system disorders
    Febrile neutropenia 0/3 (0%) 4/7 (57.1%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 2/5 (40%) 2/4 (50%) 17/56 (30.4%)
    Thrombocytopenia 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Cardiac disorders
    Atrial fibrillation 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Acute myocardial infarction 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Cardiac arrest 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Endocrine disorders
    Hyperthyroidism 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Gastrointestinal disorders
    Gastrointestinal hemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Colitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Dysphagia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Enterocolitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Mouth haemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    General disorders
    Pyrexia 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Mucosal inflammation 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Asthenia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Immune system disorders
    Cytokine release syndrome 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Infections and infestations
    Sepsis 0/3 (0%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 9/56 (16.1%)
    Pneumonia 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Cellulitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Bacteraemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Device related infection 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Urinary tract infection 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Bronchitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Enterocolitis infectious 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Fungaemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Herpes zoster disseminated 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Streptococcal bacteraemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Abscess intestinal 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Actinomycosis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Cerebral toxoplasmosis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Diverticulitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Enterococcal bacteraemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Lung infection 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Perirectal abscess 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Pneumonia fungal 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Pyelonephritis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Viral infection 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Injury, poisoning and procedural complications
    Subdural haemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Subdural haematoma 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Investigations
    Ejection fraction decreased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Platelet count decreased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Metabolism and nutrition disorders
    Hyponatraemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Dehydration 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Musculoskeletal and connective tissue disorders
    Muscular weakness 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Nervous system disorders
    Cerebral haemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Haemorrhage intracranial 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Nervous system disorder 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Renal and urinary disorders
    Urethral haemorrhage 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Reproductive system and breast disorders
    Pelvic pain 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Haemoptysis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Pneumonitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Respiratory distress 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Pneumonia aspiration 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Tachypnoea 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Skin and subcutaneous tissue disorders
    Acute febrile neutrophilic dermatosis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Rash maculo-papular 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Purpura 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Vascular disorders
    Capillary leak syndrome 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Hypertension 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Malignant hypertension 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Other (Not Including Serious) Adverse Events
    Part 1: 800 mg/Day Part 1: 1000 mg/Day Part 1: 1200 mg/Day Part 1: 1400 mg/Day Part 1: 2000 mg/Day Part 1: 3000 mg/Day Part 1: 4000 mg/Day Part 1: 5000 mg/Day Part 2: 3000 mg/Day
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/3 (100%) 7/7 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 6/6 (100%) 5/5 (100%) 4/4 (100%) 56/56 (100%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/3 (33.3%) 5/7 (71.4%) 1/3 (33.3%) 3/3 (100%) 1/3 (33.3%) 1/6 (16.7%) 2/5 (40%) 2/4 (50%) 22/56 (39.3%)
    Anaemia 0/3 (0%) 1/7 (14.3%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 2/5 (40%) 3/4 (75%) 15/56 (26.8%)
    Thrombocytopenia 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 3/4 (75%) 9/56 (16.1%)
    Neutropenia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 2/4 (50%) 4/56 (7.1%)
    Leukocytosis 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Spleen disorder 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Splenic infarction 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Pancytopenia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 5/56 (8.9%)
    Cardiac disorders
    Tachycardia 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/5 (20%) 0/4 (0%) 1/56 (1.8%)
    Atrial fibrillation 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Cardiac failure congestive 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 2/56 (3.6%)
    Sinus tachycardia 0/3 (0%) 0/7 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Acute myocardial infarction 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Bradycardia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 1/56 (1.8%)
    Palpitations 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Ear and labyrinth disorders
    Deafness 0/3 (0%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Eye disorders
    Conjunctival haemorrhage 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Conjunctivitis 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 1/56 (1.8%)
    Periorbital oedema 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 0/5 (0%) 0/4 (0%) 7/56 (12.5%)
    Vision blurred 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Eye swelling 0/3 (0%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Blepharitis 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Cataract 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Conjunctival hyperaemia 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Diplopia 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Eyelid oedema 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Lacrimation increased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 1/56 (1.8%)
    Photophobia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Trichiasis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Vitreous floaters 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Gastrointestinal disorders
    Diarrhoea 3/3 (100%) 2/7 (28.6%) 1/3 (33.3%) 2/3 (66.7%) 1/3 (33.3%) 3/6 (50%) 4/5 (80%) 2/4 (50%) 27/56 (48.2%)
    Nausea 3/3 (100%) 1/7 (14.3%) 3/3 (100%) 3/3 (100%) 0/3 (0%) 3/6 (50%) 1/5 (20%) 3/4 (75%) 24/56 (42.9%)
    Vomiting 0/3 (0%) 3/7 (42.9%) 1/3 (33.3%) 3/3 (100%) 0/3 (0%) 3/6 (50%) 2/5 (40%) 3/4 (75%) 18/56 (32.1%)
    Abdominal pain 1/3 (33.3%) 0/7 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 2/6 (33.3%) 0/5 (0%) 1/4 (25%) 8/56 (14.3%)
    Constipation 0/3 (0%) 2/7 (28.6%) 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 10/56 (17.9%)
    Gingival bleeding 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Mouth ulceration 1/3 (33.3%) 0/7 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Stomatitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 1/6 (16.7%) 0/5 (0%) 1/4 (25%) 4/56 (7.1%)
    Abdominal discomfort 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Abdominal distension 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Abdominal pain lower 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Angina bullosa haemorrhagica 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Dyspepsia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 1/4 (25%) 1/56 (1.8%)
    Abdominal pain upper 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 1/56 (1.8%)
    Anorectal discomfort 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 1/56 (1.8%)
    Ascites 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Breath odour 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Dental caries 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Dry mouth 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Dysphagia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Flatulence 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Gastritis 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Gastrointestinal haemorrhage 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Gingival hyperplasia 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Haematemesis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Haematochezia 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Haemorrhoids 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 5/56 (8.9%)
    Ileus 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Large intestinal ulcer 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Lip ulceration 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Melaena 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Mouth haemorrhage 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Oral pain 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Proctalgia 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Proctitis 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Retching 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Salivary hypersecretion 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Small intestinal obstruction 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Swollen tongue 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Tongue disorder 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Tongue ulceration 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Gastrooesophageal reflux disease 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Haemorrhoidal haemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    General disorders
    Fatigue 3/3 (100%) 3/7 (42.9%) 2/3 (66.7%) 2/3 (66.7%) 1/3 (33.3%) 2/6 (33.3%) 1/5 (20%) 3/4 (75%) 25/56 (44.6%)
    Pyrexia 2/3 (66.7%) 3/7 (42.9%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 1/5 (20%) 1/4 (25%) 8/56 (14.3%)
    Oedema peripheral 1/3 (33.3%) 2/7 (28.6%) 1/3 (33.3%) 2/3 (66.7%) 0/3 (0%) 2/6 (33.3%) 0/5 (0%) 0/4 (0%) 8/56 (14.3%)
    Chills 0/3 (0%) 1/7 (14.3%) 1/3 (33.3%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 2/4 (50%) 3/56 (5.4%)
    Face oedema 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 2/4 (50%) 6/56 (10.7%)
    Mucosal dryness 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Asthenia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/5 (20%) 0/4 (0%) 4/56 (7.1%)
    Chest pain 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 1/56 (1.8%)
    Malaise 1/3 (33.3%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Mucosal inflammation 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Axillary pain 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Catheter site erythema 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Feeling of body temperature change 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Hypothermia 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Infusion site erythema 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Infusion site swelling 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Injection site haemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Nodule 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Non-cardiac chest pain 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Pain 0/3 (0%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Oedema 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 1/3 (33.3%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Cholelithiasis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Hepatic lesion 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Hepatosplenomegaly 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Liver disorder 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Immune system disorders
    Drug hypersensitivity 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Infections and infestations
    Pneumonia 0/3 (0%) 2/7 (28.6%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/5 (20%) 0/4 (0%) 6/56 (10.7%)
    Candidiasis 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Oral herpes 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Sepsis 0/3 (0%) 0/7 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 10/56 (17.9%)
    Clostridial infection 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Device related infection 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 1/56 (1.8%)
    Streptococcal bacteraemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Bacteraemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 6/56 (10.7%)
    Bronchitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 1/56 (1.8%)
    Cellulitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Clostridium difficile colitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Enterobacter infection 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Enterococcal bacteraemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Enterocolitis infectious 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Fungaemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Herpes zoster disseminated 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Lung infection 0/3 (0%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Mucosal infection 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Nasopharyngitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Pneumonia klebsiella 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Pneumonia staphylococcal 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Skin candida 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Urinary tract infection 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Urinary tract infection bacterial 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Oral candidiasis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 5/56 (8.9%)
    Upper respiratory tract infection 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Influenza A 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Injury, poisoning and procedural complications
    Fall 0/3 (0%) 0/7 (0%) 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Contusion 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Muscle strain 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Post procedural haemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 2/56 (3.6%)
    Subdural haemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Investigations
    Aspartate aminotransferase increased 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 1/6 (16.7%) 1/5 (20%) 1/4 (25%) 13/56 (23.2%)
    Alanine aminotransferase increased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 1/5 (20%) 1/4 (25%) 6/56 (10.7%)
    Blood alkaline phosphatase increased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 1/5 (20%) 1/4 (25%) 10/56 (17.9%)
    Transaminases increased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 1/5 (20%) 1/4 (25%) 5/56 (8.9%)
    Blood bilirubin increased 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 7/56 (12.5%)
    Blood uric acid increased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 2/4 (50%) 0/56 (0%)
    Electrocardiogram QT prolonged 1/3 (33.3%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Platelet count decreased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 12/56 (21.4%)
    Cardiac murmur 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Ejection fraction decreased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 2/56 (3.6%)
    International normalised ratio increased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Myeloblast count increased 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Neutrophil count decreased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 6/56 (10.7%)
    Spleen palpable 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Weight decreased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Weight increased 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    White blood cell count decreased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 7/56 (12.5%)
    White blood cell count increased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Lymphocyte count decreased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 7/56 (12.5%)
    Blood cholesterol increased 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Metabolism and nutrition disorders
    Decreased appetite 1/3 (33.3%) 3/7 (42.9%) 0/3 (0%) 2/3 (66.7%) 1/3 (33.3%) 2/6 (33.3%) 2/5 (40%) 2/4 (50%) 20/56 (35.7%)
    Hypokalaemia 2/3 (66.7%) 0/7 (0%) 1/3 (33.3%) 3/3 (100%) 0/3 (0%) 1/6 (16.7%) 2/5 (40%) 2/4 (50%) 13/56 (23.2%)
    Hypocalcaemia 1/3 (33.3%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 1/5 (20%) 1/4 (25%) 8/56 (14.3%)
    Hyponatraemia 0/3 (0%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 0/5 (0%) 1/4 (25%) 5/56 (8.9%)
    Hypomagnesaemia 1/3 (33.3%) 0/7 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 2/4 (50%) 10/56 (17.9%)
    Hyperglycaemia 0/3 (0%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 9/56 (16.1%)
    Dehydration 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 2/6 (33.3%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Hypophosphataemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 7/56 (12.5%)
    Electrolyte imbalance 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Fluid overload 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Hyperkalaemia 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Hyperphosphataemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Hypoalbuminaemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 8/56 (14.3%)
    Metabolic acidosis 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Tumour lysis syndrome 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Hyperuricaemia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/3 (0%) 1/7 (14.3%) 1/3 (33.3%) 2/3 (66.7%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 1/4 (25%) 5/56 (8.9%)
    Arthralgia 1/3 (33.3%) 2/7 (28.6%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Pain in extremity 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Muscular weakness 0/3 (0%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Myalgia 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Groin pain 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Musculoskeletal stiffness 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 1/56 (1.8%)
    Soft tissue mass 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Tendon pain 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Leukaemia cutis 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Nervous system disorders
    Dysgeusia 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 2/3 (66.7%) 2/3 (66.7%) 2/6 (33.3%) 0/5 (0%) 2/4 (50%) 7/56 (12.5%)
    Headache 0/3 (0%) 2/7 (28.6%) 1/3 (33.3%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 1/4 (25%) 6/56 (10.7%)
    Dizziness 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 9/56 (16.1%)
    Lethargy 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 1/56 (1.8%)
    Presyncope 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 1/56 (1.8%)
    Somnolence 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Tremor 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 5/56 (8.9%)
    Balance disorder 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Cerebral haemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Clumsiness 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Convulsion 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Dysarthria 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Hypersomnia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Hypoaesthesia 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Memory impairment 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Paraesthesia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Restless legs syndrome 0/3 (0%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Sensory disturbance 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Psychiatric disorders
    Insomnia 1/3 (33.3%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Agitation 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 1/5 (20%) 0/4 (0%) 1/56 (1.8%)
    Anxiety 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 1/56 (1.8%)
    Depression 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Mental status changes 1/3 (33.3%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Confusional state 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Delirium 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Hallucination 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Restlessness 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Renal and urinary disorders
    Renal failure acute 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Urethral haemorrhage 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Urinary retention 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Urinary tract obstruction 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Reproductive system and breast disorders
    Pelvic pain 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/3 (0%) 2/7 (28.6%) 0/3 (0%) 1/3 (33.3%) 2/3 (66.7%) 4/6 (66.7%) 2/5 (40%) 2/4 (50%) 13/56 (23.2%)
    Dyspnoea 2/3 (66.7%) 1/7 (14.3%) 0/3 (0%) 3/3 (100%) 1/3 (33.3%) 1/6 (16.7%) 2/5 (40%) 1/4 (25%) 7/56 (12.5%)
    Epistaxis 1/3 (33.3%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/5 (0%) 1/4 (25%) 4/56 (7.1%)
    Hypoxia 1/3 (33.3%) 2/7 (28.6%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 1/5 (20%) 0/4 (0%) 3/56 (5.4%)
    Haemoptysis 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 1/4 (25%) 0/56 (0%)
    Productive cough 1/3 (33.3%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Rhinorrhoea 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Dysphonia 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Oropharyngeal pain 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 3/56 (5.4%)
    Pleural effusion 0/3 (0%) 2/7 (28.6%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Pneumonitis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Respiratory failure 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Acute pulmonary oedema 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Atelectasis 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Dyspnoea exertional 0/3 (0%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Lung infiltration 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Pharyngeal erythema 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Pharyngeal haemorrhage 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Pleuritic pain 0/3 (0%) 0/7 (0%) 1/3 (33.3%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Pulmonary oedema 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Respiratory distress 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Rhonchi 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Sneezing 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Tachypnoea 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 2/56 (3.6%)
    Wheezing 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Skin and subcutaneous tissue disorders
    Petechiae 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 3/6 (50%) 0/5 (0%) 1/4 (25%) 1/56 (1.8%)
    Ecchymosis 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 1/6 (16.7%) 1/5 (20%) 0/4 (0%) 0/56 (0%)
    Rash maculo-papular 0/3 (0%) 1/7 (14.3%) 1/3 (33.3%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 7/56 (12.5%)
    Alopecia 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Erythema 0/3 (0%) 0/7 (0%) 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Hyperhidrosis 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Hair colour changes 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 0/5 (0%) 0/4 (0%) 9/56 (16.1%)
    Pruritus 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 2/4 (50%) 0/56 (0%)
    Purpura 1/3 (33.3%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Rash 0/3 (0%) 0/7 (0%) 0/3 (0%) 2/3 (66.7%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 10/56 (17.9%)
    Skin exfoliation 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Acute febrile neutrophilic dermatosis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Blister 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Blood blister 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Drug eruption 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Facial wasting 1/3 (33.3%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Hair disorder 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Hair growth abnormal 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Ingrowing nail 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Nail disorder 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Pain of skin 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Rash erythematous 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/5 (20%) 0/4 (0%) 1/56 (1.8%)
    Rash papular 0/3 (0%) 0/7 (0%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Rash pruritic 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Skin mass 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Skin tightness 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Skin ulcer 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)
    Dry skin 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Swelling face 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 4/56 (7.1%)
    Palmar-plantar erythrodysaesthesia syndrome 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Vascular disorders
    Hypertension 0/3 (0%) 1/7 (14.3%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/6 (33.3%) 0/5 (0%) 2/4 (50%) 8/56 (14.3%)
    Hypotension 1/3 (33.3%) 1/7 (14.3%) 0/3 (0%) 1/3 (33.3%) 0/3 (0%) 1/6 (16.7%) 0/5 (0%) 0/4 (0%) 3/56 (5.4%)
    Capillary leak syndrome 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/5 (0%) 1/4 (25%) 0/56 (0%)
    Deep vein thrombosis 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 1/56 (1.8%)
    Flushing 0/3 (0%) 0/7 (0%) 0/3 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/5 (0%) 0/4 (0%) 0/56 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Medical Director
    Organization Daiichi Sankyo Inc.
    Phone 908-992-6400
    Email CTRinfo@dsi.com
    Responsible Party:
    Daiichi Sankyo, Inc.
    ClinicalTrials.gov Identifier:
    NCT01349049
    Other Study ID Numbers:
    • PLX108-05
    First Posted:
    May 6, 2011
    Last Update Posted:
    Mar 2, 2020
    Last Verified:
    Feb 1, 2020