SOPRA: Selinexor (KPT-330) in Older Patients With Relapsed AML

Sponsor
Karyopharm Therapeutics Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT02088541
Collaborator
(none)
317
78
5
46.3
4.1
0.1

Study Details

Study Description

Brief Summary

This is a randomized, multicenter, open-label, phase 2 study of the SINE compound, selinexor given orally versus specified investigator choices (one of three potential salvage therapies). Participants age ≥ 60 years with relapsed or refractory AML of any type except for AML M3, after one prior therapy only, who have never undergone and who are not currently eligible for stem cell transplantation and are currently deemed unfit for intensive chemotherapy.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This is a randomized, multicenter, open-label phase 2 study of the SINE compound, selinexor given orally versus restricted investigator choice (i.e., one of three potential salvage therapies).

Participants who have never been transplant eligible, are currently deemed unfit for intensive chemotherapy, ≥ 60 years old, who have AML (except Acute Promyelocytic Leukemia: APL, AML M3) after one prior treatment of either hypomethylating agent or a regimen including Ara-C, and are meeting the inclusion and exclusion criteria will be randomized to receive either oral selinexor or physician's choice (one of three potential treatments: best supportive care (BSC) alone, or BSC + hypomethylating agent, or BSC + low dose Ara-C until disease progression, death or intolerance has occurred.

Study Design

Study Type:
Interventional
Actual Enrollment :
317 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open Label, Phase 2 Study of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Versus Specified Physician's Choice in Patients ≥ 60 Years Old With Relapsed or Refractory Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy and/or Transplantation
Study Start Date :
Mar 1, 2014
Actual Primary Completion Date :
Jan 8, 2018
Actual Study Completion Date :
Jan 8, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Selinexor approximately 55 mg/m^2 (60 to 120 mg based on BSA)

Participants under protocol versions (PV) less than (<) 5.0 (those who had one prior line of acute myeloid leukemia (AML) therapy), receive oral selinexor tablets at a dose of approximately 55 mg/m^2 (milligrams per square meter) (60 to 120 mg based on body surface area [BSA]) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle).

Drug: Selinexor
Selinexor oral tablet.
Other Names:
  • KPT-330
  • Experimental: Selinexor 60 mg (PV <5) (Equivalent to 35 mg/m^2)

    Participants under PV < 5.0 (those who had one prior line of AML therapy), receive oral selinexor tablets at a fixed dose of 60 mg (equivalent to 35 mg/m^2), based on BSA, twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle).

    Drug: Selinexor
    Selinexor oral tablet.
    Other Names:
  • KPT-330
  • Experimental: Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2)

    Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), receive oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle).

    Drug: Selinexor
    Selinexor oral tablet.
    Other Names:
  • KPT-330
  • Active Comparator: Physician's Choice 1 (PV <5)

    Participants under PV < 5.0 (those who had one prior line of AML therapy) received Best Supportive Care (BSC) which included blood product transfusions, antimicrobials, growth factors as needed, and hydroxyurea.

    Drug: Hydroxyurea
    Other Names:
  • Hydroxycarbamide
  • Active Comparator: Physician's Choice 2 (PV >=5)

    Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.

    Drug: Ara-C
    Ara-C Subcutaneous Injection.
    Other Names:
  • Cytarabine
  • Cytosine arabinoside
  • Cytosar-U
  • Depocyt
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Survival [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)]

      Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact.

    Secondary Outcome Measures

    1. Percentage of Participants With Overall Survival of at Least 3 Months (OS3.0) [From randomization (Day 1) up to 3 months]

      Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.

    2. Percentage of Participants With Complete Remission Rate (CRR) for Those Who Achieved Complete Remission (CR) [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)]

      CRR was analyzed using International Working Group (IWG) 2003 criteria, as the difference in the proportions of participants with IWG results of CR. CR per IWG 2003 criteria was defined as morphologic presence of < 5 percentage (%) myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood absolute neutrophil count (ANC) > 1000 cells/microliter (microL) and platelet count > 100,000/microL, with no need for red blood cell (RBC) transfusions), and the absence of extramedullary disease.

    3. Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission (CR) [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)]

      DFS for CRR based on IWG criteria, was calculated from the first date of response of CR to the date of progression or recurrence, or date of death if progression or recurrence did not occur. Participants who discontinued prior to disease progression or recurrence or did not progress as of the time of the analysis were censored at the time of last radiologic assessment. CR per IWG 2003 criteria was defined as morphologic presence of < 5 % myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease.

    4. Percentage of Participants With Modified Complete Remission Rate (mCRR) for Those Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (Cri) [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)]

      mCRR was defined as the point estimate of the percentage of participants who had CR, CRi, or CRp. Responses defined as per IWG 2003 response criteria: Morphologic CR:< 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.

    5. Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission or CR With Incomplete Hematologic Recovery (CRi) or Complete Remission With Incomplete Platelet Recovery (CRp) [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)]

      DFS based on IWG criteria was defined as the duration from start of the complete response achieved until disease progression or death from any cause. Responses defined by IWG 2003 Response Criteria: Morphologic CR: < 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.

    6. Percentage of Participants With Overall Response Rate (ORR) [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)]

      Overall response rate was defined as the point estimate of the percentage of participants who achieved CR (disappearance of all target and non-target lesions), partial response (PR) (>=30 % decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions). CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. CRp; All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L) and morphologic leukemia-free state (MLFS); morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%, in absence of blasts with Auer rods, no hematologic recovery required.

    7. Duration of Response (DOR) [Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)]

      DOR was calculated from date of response of CR, CRi, CRp, MLFS, or PR to date of progression or recurrence based on IWG criteria. CR: <5% myeloblasts in bone marrow,absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL, platelet count > 100,000/microL, no need for RBC transfusions), absence of extramedullary disease. PR: No circulating blasts, neutrophil count > =1.0 x10^9/L, platelet count >= 100 x10^9/L, >= 50 % reduction in bone marrow blast to 6% to 25%, or blasts less than or equal to (<=) 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), CRi; < 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS: morphologic bone marrow blast clearance to < 5% in marrow sample, <= 200 cells enumerated/cellularity is ≥ 10%, in absence of blasts with Auer rods, no hematologic recovery required.

    8. Percentage of Participants With Disease Control Rate (DCR) [Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria]

      DCR:Point estimate of % of participants with CR,CRi,CRp,MLFS,PR, or SD for <=4 weeks.CR:<5% myeloblasts in bone marrow (BM),absence of circulating blasts,hematologic recovery(peripheral blood ANC >1000 cells/microL and platelet count >100,000/microL, no need of RBC transfusions),absence of extramedullary disease. PR:No circulating blasts,Neutrophil count >=1.0 x10^9/L, Platelet count >= 100*10^9/L, >=50% reduction in BM blast to 6% to 25%, or blasts <=5% if Auer rods are present.CRp:All criteria for CR except for residual neutropenia (<1*10^9/L) or thrombocytopenia(<100 x10^9/L),CRi;< 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS:morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%,in absence of blasts with Auer rods,no hematologic recovery required,SD:failure to achieve a response but not meeting criteria for disease progression over period of >4 weeks.

    9. Duration of Disease Control Rate [Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria]

      Duration of DCR calculated for all participants with DCR. CR: < 5% myeloblasts in BM, absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL and platelet count > 100,000/microL, no need for RBC transfusions), absence of extra medullary disease. PR: No circulating blasts, Neutrophil count >=1.0 x 10^9/L, Platelet count >= 100 x 10^9/L, >= 50 % reduction in BM blast to 6% to 25%, or blasts <= 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1 x 10^9/L) or thrombocytopenia (<100 x 10^9/L), CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS; morphologic BM blast clearance to < 5% in a marrow sample in which <=200 cells enumerated/cellularity is >= 10%, in absence of blasts with Auer rods, no hematologic recovery required and SD; failure to achieve a response but not meeting criteria for disease progression over period of > 4 weeks.

    10. Change From Baseline in Quality of Life (QoL) and Patient-Reported Outcomes (Functional Assessment of Cancer Therapy -Leukemia [FACT-Leu] [Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)]

      QoL was assessed by the FACT-Leu. FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific sub-scale (17 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI; total of 31 items) was the primary measurement of interest, comprising the Physical and Functional sub-scales plus the leukemia - specific sub-scale. Each item was rated on a 5-point Likert scale. Range from 0 = (Not at all) to 4 = (Very much); therefore, the TOI had a score ranging from 0 to 124. Higher scores indicated improvement in well being. The QoL assessment was performed at baseline (prior to first dose of study treatment), Day 1 of each cycle on or after the second, and at the final visit.

    11. Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Health Questionnaire Visual Analogue Scale (VAS) [Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)]

      EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    60 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Age ≥ 60 years with relapsed or refractory AML of any type except for acute promyelocytic leukemia (APL; AML M3), after at least 1 prior AML therapy , who have never undergone, and who are not currently eligible for, stem cell transplantation, and are currently deemed unfit for intensive chemotherapy.

    • Eastern Cooperative Oncology Group (ECOG) ≤ 2.

    • Must have available archival or recently acquired bone marrow biopsy/aspiration or tumor tissue for central review to be eligible.

    • Relapsed or refractory AML, defined as either: recurrence of disease after a complete remission (CR), or failure to achieve CR with initial therapy.

    • Must have received at least 1 prior line of AML therapy given at standard doses and must have progressed after their most recent therapy. Prior therapy must have included: a hypomethylating agent with at least 2 cycles.

    • At least 2 weeks must have elapsed since the last anti-leukemia treatment (with the exception of hydroxyurea) before first dose in this study.

    Exclusion Criteria:
    • Treatment with any investigational agent within 3 weeks prior to first dose in this study.

    • Presence of central nervous system (CNS) leukemia.

    • In blast transformation of chronic myeloid leukemia (CML). Prior myelodysplastic syndrome (MDS) is acceptable; prior treatment for MDS does not count as an AML therapy.

    • Major surgery within 2 weeks of first dose of study drug. Participants must have recovered from the effects of any surgery performed greater than 2 weeks previously.

    • Concurrent active malignancy under treatment.

    • Known active hepatitis B virus (HBV) or C virus (HCV) infection; or known to be positive for HCV ribonucleic acid (RNA) or HBsAg (HBV surface antigen).

    • Known HIV infection.

    • Unable to swallow tablets, or participants with malabsorption syndrome, or any other disease significantly affecting gastrointestinal function.

    • Participants whose AML is classified as favorable according to the European LeukemiaNet (ELN) disease risk assessment.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Jonsson Comprehensive Cancer Center / University of California, Los Angeles Los Angeles California United States 90024
    2 Sutter Oncology & Hematology Sacramento California United States 95816
    3 Stanford Cancer Institute / Stanford University Stanford California United States 94304
    4 Colorado Blood Cancer Institute/Sarah Cannon Research Institute Denver Colorado United States 80218
    5 Yale Cancer Center / Yale University New Haven Connecticut United States 06510
    6 H. Lee Moffitt Cancer Center and Research Institute Tampa Florida United States 33612
    7 Winship Cancer Institute / Emory University Atlanta Georgia United States 30322
    8 Northwestern University Chicago Illinois United States 60611
    9 University of Chicago Medicine Chicago Illinois United States 60637
    10 University of Kansas Hospital Kansas City Kansas United States 66160
    11 Sidney Kimmel Comprehensive Cancer Center / John Hopkins University Baltimore Maryland United States 21287
    12 University of Massachusetts Medical School Worcester Massachusetts United States 01655
    13 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109-0944
    14 Hackensack University Medical Center Hackensack New Jersey United States 07601
    15 Roswell Park Cancer Institute Buffalo New York United States 14263
    16 Westchester Medical Center / New York Medical College Hawthorne New York United States 10532
    17 Memorial Sloan Kettering Cancer Center New York New York United States 10065
    18 New York Presbyterian Hospital / Weill Cornell Medical College New York New York United States 10065
    19 Duke Cancer Care Durham North Carolina United States 27705
    20 Gabrail Cancer Center Canton Ohio United States 44718
    21 Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
    22 Milton S. Hershey Medical Center / Penn State Hershey Pennsylvania United States 17033
    23 Tennessee Oncology/Sarah Cannon Research Institute Nashville Tennessee United States 37203
    24 Vanderbilt-Ingram Cancer Center / Vanderbilt University Nashville Tennessee United States 37215
    25 MD Anderson Cancer Center / University of Texas Houston Texas United States 77030
    26 Texas Transplant Institute/Sarah Cannon Research Institute San Antonio Texas United States 78229
    27 Tom Baker Cancer Centre Calgary Alberta Canada T2N 4N2
    28 University of Alberta Edmonton Alberta Canada T6G 2G3
    29 Sir Mortimer B. Davis Jewish General Hospital / McGill University Montreal Quebec Canada H2W1S6
    30 Aarhus University Hospital Aarhus Denmark
    31 Department of Haematology, National University Hospital, Rigshospitalet Copenhagen Denmark
    32 Herlev Hospital Herlev Denmark
    33 Odense University Hospital, Department of Hematology Odense Denmark
    34 CHU Bordeaux- Hôpital Haut Lévêque Bordeaux France
    35 Centre Hospitalier Lyon Lyon France
    36 Hopital Saint Louis Paris France
    37 Hôpital Avicenne Paris France
    38 Institut Universitaire du Cancer Toulouse Toulouse France
    39 Stellvertretende Klinikleiterin Charité, Campus Benjamin Franklin Berlin Germany 12203
    40 Ev. Diakonie-Krankenhaus Gemeinnutzige GMBH Medizinische Klinik 2 Bremen Germany
    41 UNIVERSITÄTSKLINIKUM TU DRESDEN Medizinische Klinik und Poliklinik I, Dresden Germany
    42 University Hospital Frankfurt Frankfurt Germany
    43 Medizinische Hochschule Hannover (Hannover Medical School) Dept. of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation Hanover Germany
    44 Abteilung Hämatologie, internistische Onkologie und Hämostaseologie Leipzig Germany
    45 UNIVERSITY HOSPITAL OF MÜNSTER Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster Münster Germany
    46 Universitätsklinikum Ulm ULM Germany
    47 Sororka MC Beer Sheva Israel 85025
    48 Rambam Health Care Campus Haifa Israel 3109601
    49 Wolfson Medical Center Holon Israel
    50 Hadassah Medical Center Jerusalem Israel 91120
    51 Rabin Medical Center Petach Tikva Israel 4941492
    52 Tel Aviv Sourasky Medical Centre Tel Aviv Israel
    53 Chaim Sheba Medical Center Tel Hashomer Israel 52621
    54 AOU Ospedali Riuniti di Ancona Ancona Italy
    55 A.O Spedali Civili di Brescia Brescia Italy
    56 AORN Cardarelli / UOSC di Ematologia con TMO Naples Italy
    57 AMC, Academisch Medisch Centrum Afdeling Klinische Hematologie Amsterdam Netherlands
    58 VU University Medical Center Amsterdam Netherlands
    59 Universitair Medisch Centrum Groningen Department of Haematology Groningen Netherlands
    60 Radboud University Medical Center Department of Haematology (476) Nijmegen Netherlands
    61 Erasmus MC, location Daniel den Hoed Rotterdam Netherlands
    62 University Medical Center Utrecht Utrecht Netherlands
    63 Isala Kliniecken Zwolle Zwolle Netherlands
    64 Wojewódzki Szpital Specjalistyczny im. M. Kopernika, Klinika Hematologii Lodz Poland
    65 Samodzielny Publiczny Zakład Opieki Zdrowotnej Ministerstwa Spraw Wewnętrznych Olsztyn Poland
    66 Instytut Hematologii i Transfuzjologii Warszawa Poland
    67 Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu Wroclaw Poland
    68 ICO Badalona Badalona Spain 08916
    69 Hospital del Mar Barcelona Spain
    70 Hospital Universitario de Salamanca Servicio de Hematologia Salamanca Spain
    71 Hospital Universitario y Politécnico La Fe Valencia Spain
    72 Northwick Park Hospital Harrow England United Kingdom HA1 3UJ
    73 Royal Liverpool University Hospital, Dept of Cellular and Molecular Physiology, Molecular and Clinical Cancer Medicine Liverpool Lancashire United Kingdom L7 8XP
    74 Royal Marsden NHS Trust Sutton Surrey United Kingdom SM2 5PT
    75 University Hospital Wales Cardiff Wales United Kingdom CF14 4XW
    76 Hull and East Yorkshire Hospitals NHS Trust Queens Centre for Oncology and Haematology Hull Yorkshire United Kingdom HU3 2JZ
    77 Ninewells Hospital and Medical School NHS Tayside Dundee United Kingdom DD1 9SY
    78 Plymouth Hospitals NHS Trust/Derriford Hospital Plymouth United Kingdom

    Sponsors and Collaborators

    • Karyopharm Therapeutics Inc

    Investigators

    • Study Director: Michael Kauffman, MD, PhD, Karyopharm Therapeutics Inc

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Karyopharm Therapeutics Inc
    ClinicalTrials.gov Identifier:
    NCT02088541
    Other Study ID Numbers:
    • KCP-330-008
    First Posted:
    Mar 17, 2014
    Last Update Posted:
    Oct 8, 2020
    Last Verified:
    Sep 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Karyopharm Therapeutics Inc
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60 mg (PV <5) (Equivalent to 35 mg/m^2) Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under protocol versions (PV) less than (<) 5.0 (those who had one prior line of acute myeloid leukemia (AML) therapy), received oral selinexor tablets at a dose of approximately 55 mg/m^2 (milligrams per square meter) (60 to 120 mg based on body surface area [BSA]) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a fixed dose of 60 mg (equivalent to 35 mg/m^2), twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV greater than or equal to (>=) 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy) received Best Supportive Care (BSC) which included blood product transfusions, antimicrobials, growth factors as needed, and hydroxyurea. Participants under PV>= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Period Title: Overall Study
    STARTED 71 27 117 44 58
    Safety Population 71 27 115 39 45
    Intent-to-treat (ITT) Population 0 0 118 0 57
    COMPLETED 0 0 0 0 0
    NOT COMPLETED 71 27 117 44 58

    Baseline Characteristics

    Arm/Group Title Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60 mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5) Total
    Arm/Group Description Participants under PV < 5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a dose of approximately 55 mg/m^2 (60 to 120 mg based on BSA) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a fixed dose of 60 mg (equivalent to 35 mg/m^2), based on BSA, twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy) received Best Supportive Care (BSC) which included blood product transfusions, antimicrobials, growth factors as needed, and hydroxyurea. Participants under PV>= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals. Total of all reporting groups
    Overall Participants 71 27 115 39 45 297
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    72.4
    (6.49)
    73.2
    (4.64)
    73.6
    (5.99)
    72.6
    (5.24)
    74.2
    (5.92)
    73.2
    (5.90)
    Sex: Female, Male (Count of Participants)
    Female
    26
    36.6%
    11
    40.7%
    46
    40%
    17
    43.6%
    15
    33.3%
    115
    38.7%
    Male
    45
    63.4%
    16
    59.3%
    69
    60%
    22
    56.4%
    30
    66.7%
    182
    61.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    4
    5.6%
    3
    11.1%
    9
    7.8%
    4
    10.3%
    6
    13.3%
    26
    8.8%
    Not Hispanic or Latino
    65
    91.5%
    23
    85.2%
    93
    80.9%
    34
    87.2%
    31
    68.9%
    246
    82.8%
    Unknown or Not Reported
    2
    2.8%
    1
    3.7%
    13
    11.3%
    1
    2.6%
    8
    17.8%
    25
    8.4%
    Race/Ethnicity, Customized (Count of Participants) [Number]
    White
    67
    94.4%
    22
    81.5%
    95
    82.6%
    39
    100%
    37
    82.2%
    260
    87.5%
    Black or African American
    3
    4.2%
    1
    3.7%
    3
    2.6%
    0
    0%
    0
    0%
    7
    2.4%
    Asian
    0
    0%
    2
    7.4%
    0
    0%
    0
    0%
    0
    0%
    2
    0.7%
    Other
    0
    0%
    1
    3.7%
    15
    13%
    0
    0%
    6
    13.3%
    22
    7.4%
    Unknown
    1
    1.4%
    1
    3.7%
    2
    1.7%
    0
    0%
    2
    4.4%
    6
    2%

    Outcome Measures

    1. Primary Outcome
    Title Overall Survival
    Description Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact.
    Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 118 57
    Median (95% Confidence Interval) [Days]
    94.0
    170.0
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2), Physician's Choice 2 (PV >=5)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4221
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.18
    Confidence Interval (2-Sided) 95%
    0.79 to 1.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Percentage of Participants With Overall Survival of at Least 3 Months (OS3.0)
    Description Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method.
    Time Frame From randomization (Day 1) up to 3 months

    Outcome Measure Data

    Analysis Population Description
    ITT population included all participants who were randomized to study treatment under PV >=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 118 57
    Number (95% Confidence Interval) [Percentage of participants]
    53.49
    75.3%
    70.73
    262%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2), Physician's Choice 2 (PV >=5)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.9464
    Comments
    Method Log Rank
    Comments
    3. Secondary Outcome
    Title Percentage of Participants With Complete Remission Rate (CRR) for Those Who Achieved Complete Remission (CR)
    Description CRR was analyzed using International Working Group (IWG) 2003 criteria, as the difference in the proportions of participants with IWG results of CR. CR per IWG 2003 criteria was defined as morphologic presence of < 5 percentage (%) myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood absolute neutrophil count (ANC) > 1000 cells/microliter (microL) and platelet count > 100,000/microL, with no need for red blood cell (RBC) transfusions), and the absence of extramedullary disease.
    Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

    Outcome Measure Data

    Analysis Population Description
    ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 118 57
    Number (95% Confidence Interval) [Percentage of participants]
    5.1
    7.2%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2), Physician's Choice 2 (PV >=5)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0986
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    4. Secondary Outcome
    Title Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission (CR)
    Description DFS for CRR based on IWG criteria, was calculated from the first date of response of CR to the date of progression or recurrence, or date of death if progression or recurrence did not occur. Participants who discontinued prior to disease progression or recurrence or did not progress as of the time of the analysis were censored at the time of last radiologic assessment. CR per IWG 2003 criteria was defined as morphologic presence of < 5 % myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease.
    Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

    Outcome Measure Data

    Analysis Population Description
    ITT population:all participants who randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. This outcome measure(OM) was only defined for CR participants. For Physician Choice 2,there was zero CR participants."Overall Number of Participants Analyzed (N)": Number of participants evaluable for this OM.
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5, received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 6 0
    Median (95% Confidence Interval) [Days]
    121.0
    5. Secondary Outcome
    Title Percentage of Participants With Modified Complete Remission Rate (mCRR) for Those Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (Cri)
    Description mCRR was defined as the point estimate of the percentage of participants who had CR, CRi, or CRp. Responses defined as per IWG 2003 response criteria: Morphologic CR:< 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.
    Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

    Outcome Measure Data

    Analysis Population Description
    ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 118 57
    Number (95% Confidence Interval) [Percentage of participants]
    11.9
    16.8%
    3.5
    13%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2), Physician's Choice 2 (PV >=5)
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0844
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    6. Secondary Outcome
    Title Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission or CR With Incomplete Hematologic Recovery (CRi) or Complete Remission With Incomplete Platelet Recovery (CRp)
    Description DFS based on IWG criteria was defined as the duration from start of the complete response achieved until disease progression or death from any cause. Responses defined by IWG 2003 Response Criteria: Morphologic CR: < 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.
    Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

    Outcome Measure Data

    Analysis Population Description
    ITT population included all participants who were randomized to study treatment under PV >=5.0, regardless of whether or not they received study treatment. Here, "N" signifies number of participants evaluable for this outcome measure.
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5, received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 14 2
    Median (95% Confidence Interval) [Days]
    175.0
    106.0
    7. Secondary Outcome
    Title Percentage of Participants With Overall Response Rate (ORR)
    Description Overall response rate was defined as the point estimate of the percentage of participants who achieved CR (disappearance of all target and non-target lesions), partial response (PR) (>=30 % decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions). CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. CRp; All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L) and morphologic leukemia-free state (MLFS); morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%, in absence of blasts with Auer rods, no hematologic recovery required.
    Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

    Outcome Measure Data

    Analysis Population Description
    ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 118 57
    Number (95% Confidence Interval) [Percentage of participants]
    13.6
    19.2%
    8.8
    32.6%
    8. Secondary Outcome
    Title Duration of Response (DOR)
    Description DOR was calculated from date of response of CR, CRi, CRp, MLFS, or PR to date of progression or recurrence based on IWG criteria. CR: <5% myeloblasts in bone marrow,absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL, platelet count > 100,000/microL, no need for RBC transfusions), absence of extramedullary disease. PR: No circulating blasts, neutrophil count > =1.0 x10^9/L, platelet count >= 100 x10^9/L, >= 50 % reduction in bone marrow blast to 6% to 25%, or blasts less than or equal to (<=) 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), CRi; < 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS: morphologic bone marrow blast clearance to < 5% in marrow sample, <= 200 cells enumerated/cellularity is ≥ 10%, in absence of blasts with Auer rods, no hematologic recovery required.
    Time Frame Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

    Outcome Measure Data

    Analysis Population Description
    ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. Here, "N" signifies number of participants evaluable for this outcome measure.
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 16 5
    Median (95% Confidence Interval) [Days]
    204.0
    148.0
    9. Secondary Outcome
    Title Percentage of Participants With Disease Control Rate (DCR)
    Description DCR:Point estimate of % of participants with CR,CRi,CRp,MLFS,PR, or SD for <=4 weeks.CR:<5% myeloblasts in bone marrow (BM),absence of circulating blasts,hematologic recovery(peripheral blood ANC >1000 cells/microL and platelet count >100,000/microL, no need of RBC transfusions),absence of extramedullary disease. PR:No circulating blasts,Neutrophil count >=1.0 x10^9/L, Platelet count >= 100*10^9/L, >=50% reduction in BM blast to 6% to 25%, or blasts <=5% if Auer rods are present.CRp:All criteria for CR except for residual neutropenia (<1*10^9/L) or thrombocytopenia(<100 x10^9/L),CRi;< 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS:morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%,in absence of blasts with Auer rods,no hematologic recovery required,SD:failure to achieve a response but not meeting criteria for disease progression over period of >4 weeks.
    Time Frame Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria

    Outcome Measure Data

    Analysis Population Description
    ITT Population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. One participant was randomized to receive selinexor 60 mg (PV>=5) but was treated with physician's choice 2. Hence, this participant was counted under selinexor 60 mg (PV>=5).
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 118 57
    Number (95% Confidence Interval) [Percentage of participants]
    50.8
    71.5%
    40.4
    149.6%
    10. Secondary Outcome
    Title Duration of Disease Control Rate
    Description Duration of DCR calculated for all participants with DCR. CR: < 5% myeloblasts in BM, absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL and platelet count > 100,000/microL, no need for RBC transfusions), absence of extra medullary disease. PR: No circulating blasts, Neutrophil count >=1.0 x 10^9/L, Platelet count >= 100 x 10^9/L, >= 50 % reduction in BM blast to 6% to 25%, or blasts <= 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1 x 10^9/L) or thrombocytopenia (<100 x 10^9/L), CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS; morphologic BM blast clearance to < 5% in a marrow sample in which <=200 cells enumerated/cellularity is >= 10%, in absence of blasts with Auer rods, no hematologic recovery required and SD; failure to achieve a response but not meeting criteria for disease progression over period of > 4 weeks.
    Time Frame Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria

    Outcome Measure Data

    Analysis Population Description
    ITT population included all participants who were randomized to study treatment under PV>=5.0, regardless of whether or not they received study treatment. Here," N" signifies number of participants evaluable for this measure.
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 60 23
    Median (95% Confidence Interval) [Days]
    187.0
    233.0
    11. Secondary Outcome
    Title Change From Baseline in Quality of Life (QoL) and Patient-Reported Outcomes (Functional Assessment of Cancer Therapy -Leukemia [FACT-Leu]
    Description QoL was assessed by the FACT-Leu. FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific sub-scale (17 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI; total of 31 items) was the primary measurement of interest, comprising the Physical and Functional sub-scales plus the leukemia - specific sub-scale. Each item was rated on a 5-point Likert scale. Range from 0 = (Not at all) to 4 = (Very much); therefore, the TOI had a score ranging from 0 to 124. Higher scores indicated improvement in well being. The QoL assessment was performed at baseline (prior to first dose of study treatment), Day 1 of each cycle on or after the second, and at the final visit.
    Time Frame Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)

    Outcome Measure Data

    Analysis Population Description
    Per-Protocol (PP) population: all participants randomized to study treatment under PV>=5.0 who received any amount of study treatment and had no major protocol violations that compromised assessment of efficacy. Here, N= number of participants evaluable for this measure and n=participants evaluable for this outcome measure at specified categories.
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 71 34
    Baseline
    70.5
    (15.20)
    75.4
    (14.74)
    C2D1
    0.5
    (16.50)
    -1.9
    (15.18)
    C3D1
    -1.9
    (16.88)
    -5.4
    (22.25)
    C4D1
    -1.2
    (15.70)
    -7.4
    (25.41)
    C5D1
    -2.4
    (16.84)
    1.9
    (8.40)
    C6D1
    -3.4
    (15.66)
    -4.7
    (13.20)
    C7D1
    -5.0
    (17.21)
    -11.8
    (27.43)
    C8D1
    -3.9
    (15.78)
    -10.6
    (7.83)
    C9D1
    -2.7
    (7.47)
    -8.0
    (8.49)
    C10D1
    2.4
    (13.19)
    -10.7
    (12.70)
    C11D1
    -0.1
    (8.65)
    -10.0
    (9.90)
    C12D1
    -3.7
    (11.69)
    -7.0
    (16.97)
    C13D1
    -3.3
    (6.40)
    -9.0
    (NA)
    C14D1
    -4.0
    (3.46)
    -15.0
    C15D1
    1.5
    (3.54)
    -10.0
    (NA)
    C16D1
    -15.0
    (NA)
    C17D1
    -15.0
    (NA)
    -7.0
    (NA)
    C18D1
    -1.0
    (NA)
    C19D1
    -12.0
    (NA)
    C20D1
    -14.0
    (NA)
    Final visit
    2.5
    (17.71)
    -1.7
    (20.46)
    12. Secondary Outcome
    Title Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Health Questionnaire Visual Analogue Scale (VAS)
    Description EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
    Time Frame Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)

    Outcome Measure Data

    Analysis Population Description
    PP Population included all participants randomized to study treatment under PV >=5.0 who received any amount of study treatment and who had no major protocol violations that compromised assessment of efficacy. Here, N= number of participants evaluable for this measure and n =Participants evaluable for this outcome measure at specified categories
    Arm/Group Title Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    Measure Participants 71 34
    Baseline
    67.9
    (19.51)
    63.5
    (21.10)
    C2D1
    -7.5
    (23.45)
    0.8
    (15.82)
    C3D1
    -13.3
    (25.04)
    -5.2
    (23.54)
    C4D1
    -6.1
    (20.80)
    -5.0
    (11.46)
    C5D1
    -0.9
    (20.83)
    -2.0
    (15.31)
    C6D1
    -11.2
    (25.90)
    -1.4
    (24.10)
    C7D1
    -3.7
    (23.91)
    4.0
    (10.84)
    C8D1
    0.1
    (16.77)
    5.0
    (9.35)
    C9D1
    4.6
    (13.25)
    5.0
    (10.80)
    C10D1
    0.7
    (18.58)
    6.3
    (15.48)
    C11D1
    0.8
    (18.55)
    -5.0
    (21.21)
    C12D1
    3.3
    (16.63)
    -5.0
    (28.28)
    C13D1
    6.7
    (20.21)
    10.0
    (NA)
    C14D1
    6.7
    (25.66)
    15.0
    (NA)
    C15D1
    3.5
    (30.41)
    -10.0
    (NA)
    C16D1
    20.0
    (NA)
    C17D1
    25.0
    (NA)
    -5.0
    (NA)
    C18D1
    25.0
    (NA)
    C19D1
    30.0
    (NA)
    C20D1
    35.0
    (NA)

    Adverse Events

    Time Frame From start of study drug administration to 30 days after last dose of study drug (approximately 48 months)
    Adverse Event Reporting Description Same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. AEs and SAEs were collected for safety population.
    Arm/Group Title Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
    Arm/Group Description Participants under PV <5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a dose of approximately 55 mg/m^2 (60 to 120 mg based on BSA) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV <5.0 (those who had one prior line of AML therapy), received oral selinexor tablets at a fixed dose of 60 mg (equivalent to 35 mg/m^2), based on BSA, twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle). Participants under PV >=5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m^2) twice weekly, on Day 1 and 3 of each week of 4- week cycle (28 days per cycle). Participants under PV < 5.0 (those who had one prior line of AML therapy) received Best Supportive Care (BSC) which included blood product transfusions, antimicrobials, growth factors as needed, and hydroxyurea. Participants under PV >= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.
    All Cause Mortality
    Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/71 (33.8%) 3/27 (11.1%) 28/115 (24.3%) 7/39 (17.9%) 9/45 (20%)
    Serious Adverse Events
    Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 58/71 (81.7%) 15/27 (55.6%) 89/115 (77.4%) 25/39 (64.1%) 30/45 (66.7%)
    Blood and lymphatic system disorders
    Anaemia 2/71 (2.8%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 3/45 (6.7%)
    Febrile Neutropenia 16/71 (22.5%) 4/27 (14.8%) 20/115 (17.4%) 8/39 (20.5%) 16/45 (35.6%)
    Leukostasis Syndrome 0/71 (0%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 1/45 (2.2%)
    Neutropenia 1/71 (1.4%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Splenic Infarction 0/71 (0%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 1/45 (2.2%)
    Thrombocytopenia 1/71 (1.4%) 1/27 (3.7%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Cardiac disorders
    Acute Coronary Syndrome 0/71 (0%) 1/27 (3.7%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Atrial Fibrillation 2/71 (2.8%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 1/45 (2.2%)
    Bradycardia 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Cardiac Failure 1/71 (1.4%) 0/27 (0%) 3/115 (2.6%) 0/39 (0%) 0/45 (0%)
    Cardiac Failure Congestive 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Cardio-Respiratory Arrest 0/71 (0%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 1/45 (2.2%)
    Sinus Bradycardia 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Tachyarrhythmia 0/71 (0%) 1/27 (3.7%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Ventricular Fibrillation 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Ear and labyrinth disorders
    Vertigo 0/71 (0%) 1/27 (3.7%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Eye disorders
    Cataract 0/71 (0%) 0/27 (0%) 3/115 (2.6%) 0/39 (0%) 0/45 (0%)
    Gastrointestinal disorders
    Abdominal Pain Upper 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Constipation 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Diarrhoea 3/71 (4.2%) 1/27 (3.7%) 6/115 (5.2%) 0/39 (0%) 0/45 (0%)
    Diverticular Perforation 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Gastrointestinal Haemorrhage 0/71 (0%) 1/27 (3.7%) 1/115 (0.9%) 1/39 (2.6%) 0/45 (0%)
    Large Intestinal Haemorrhage 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Mouth Ulceration 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Nausea 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Tooth Loss 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Vomiting 4/71 (5.6%) 0/27 (0%) 3/115 (2.6%) 0/39 (0%) 0/45 (0%)
    General disorders
    Asthenia 3/71 (4.2%) 0/27 (0%) 2/115 (1.7%) 2/39 (5.1%) 0/45 (0%)
    Condition Aggravated 0/71 (0%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 1/45 (2.2%)
    General Physical Health Deterioration 1/71 (1.4%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 0/45 (0%)
    Malaise 0/71 (0%) 0/27 (0%) 0/115 (0%) 1/39 (2.6%) 0/45 (0%)
    Multiple Organ Dysfunction Syndrome 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Pain 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Pyrexia 4/71 (5.6%) 1/27 (3.7%) 7/115 (6.1%) 2/39 (5.1%) 1/45 (2.2%)
    Fatigue 1/71 (1.4%) 0/27 (0%) 8/115 (7%) 0/39 (0%) 0/45 (0%)
    Hepatobiliary disorders
    Cholecystitis Acute 0/71 (0%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 0/45 (0%)
    Hyperbilirubinaemia 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Infections and infestations
    Arthritis Bacterial 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Aspergillus Infection 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Biliary Sepsis 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Biliary Tract Infection 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Cellulitis 2/71 (2.8%) 0/27 (0%) 1/115 (0.9%) 1/39 (2.6%) 1/45 (2.2%)
    Clostridium Difficile Infection 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Device Related Infection 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 1/39 (2.6%) 1/45 (2.2%)
    Diverticulitis 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Escherichia Sepsis 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 1/39 (2.6%) 1/45 (2.2%)
    Fungal Infection 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Infection 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 2/45 (4.4%)
    Klebsiella Sepsis 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Laryngitis 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Lower Respiratory Tract Infection 1/71 (1.4%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Lung Infection 3/71 (4.2%) 1/27 (3.7%) 1/115 (0.9%) 3/39 (7.7%) 0/45 (0%)
    Necrotising Fasciitis 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Neutropenic Sepsis 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Penile Infection 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Perirectal Abscess 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Pneumocystis Jirovecii Pneumonia 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Pneumonia 10/71 (14.1%) 4/27 (14.8%) 10/115 (8.7%) 4/39 (10.3%) 3/45 (6.7%)
    Pneumonia Fungal 2/71 (2.8%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 1/45 (2.2%)
    Sepsis 8/71 (11.3%) 1/27 (3.7%) 3/115 (2.6%) 3/39 (7.7%) 1/45 (2.2%)
    Septic Shock 1/71 (1.4%) 0/27 (0%) 3/115 (2.6%) 1/39 (2.6%) 0/45 (0%)
    Sialoadenitis 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Sinusitis 2/71 (2.8%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Skin Infection 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Soft Tissue Infection 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Tonsillitis 0/71 (0%) 0/27 (0%) 0/115 (0%) 1/39 (2.6%) 0/45 (0%)
    Upper Respiratory Tract Infection 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Urinary Tract Infection 0/71 (0%) 0/27 (0%) 3/115 (2.6%) 1/39 (2.6%) 0/45 (0%)
    Urosepsis 0/71 (0%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 1/45 (2.2%)
    Vaginal Abscess 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Vulval Cellulitis 0/71 (0%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 1/45 (2.2%)
    Injury, poisoning and procedural complications
    Fall 0/71 (0%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 1/45 (2.2%)
    Femur Fracture 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Subarachnoid Haemorrhage 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Subdural Haematoma 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 1/39 (2.6%) 0/45 (0%)
    Subdural Haemorrhage 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Investigations
    Blood Alkaline Phosphatase Increased 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    C-Reactive Protein Increased 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Electrocardiogram Change 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Enterococcus Test Positive 0/71 (0%) 0/27 (0%) 0/115 (0%) 1/39 (2.6%) 0/45 (0%)
    Troponin T Increased 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Vitamin B12 Decreased 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Weight Decreased 1/71 (1.4%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Metabolism and nutrition disorders
    Decreased Appetite 1/71 (1.4%) 0/27 (0%) 6/115 (5.2%) 0/39 (0%) 0/45 (0%)
    Dehydration 5/71 (7%) 0/27 (0%) 2/115 (1.7%) 1/39 (2.6%) 0/45 (0%)
    Failure To Thrive 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Fluid Overload 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 1/39 (2.6%) 0/45 (0%)
    Hypercreatininaemia 0/71 (0%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 0/45 (0%)
    Hyperglycaemia 5/71 (7%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Hyperkalaemia 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Hyponatraemia 3/71 (4.2%) 1/27 (3.7%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Hypophagia 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Musculoskeletal and connective tissue disorders
    Bone Pain 0/71 (0%) 0/27 (0%) 0/115 (0%) 1/39 (2.6%) 0/45 (0%)
    Muscular Weakness 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal Cell Carcinoma 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Cerebellar Tumour 0/71 (0%) 0/27 (0%) 0/115 (0%) 1/39 (2.6%) 0/45 (0%)
    Squamous Cell Carcinoma 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Nervous system disorders
    Ataxia 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Cerebral Haemorrhage 1/71 (1.4%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 1/45 (2.2%)
    Cerebral Infarction 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Cerebrovascular Accident 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Dizziness 1/71 (1.4%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 0/45 (0%)
    Embolic Stroke 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Encephalopathy 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Haemorrhage Intracranial 2/71 (2.8%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Haemorrhagic Cerebral Infarction 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Headache 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Ischaemic Stroke 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Loss Of Consciousness 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Nervous System Disorders 8/71 (11.3%) 1/27 (3.7%) 15/115 (13%) 0/39 (0%) 1/45 (2.2%)
    Presyncope 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Syncope 2/71 (2.8%) 1/27 (3.7%) 3/115 (2.6%) 0/39 (0%) 0/45 (0%)
    Psychiatric disorders
    Confusional State 4/71 (5.6%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 0/45 (0%)
    Hallucination 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Mental Status Changes 1/71 (1.4%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 0/45 (0%)
    Organic Brain Syndrome 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Renal and urinary disorders
    Acute Kidney Injury 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Oliguria 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Renal Failure 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Reproductive system and breast disorders
    Vaginal Haemorrhage 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Failure 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Cough 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Dyspnoea 2/71 (2.8%) 1/27 (3.7%) 3/115 (2.6%) 1/39 (2.6%) 0/45 (0%)
    Epistaxis 2/71 (2.8%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 2/45 (4.4%)
    Haemoptysis 0/71 (0%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 1/45 (2.2%)
    Pleural Effusion 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 1/45 (2.2%)
    Pneumonia Aspiration 2/71 (2.8%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Pulmonary Embolism 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Pulmonary Mass 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Respiratory Failure 2/71 (2.8%) 0/27 (0%) 2/115 (1.7%) 0/39 (0%) 0/45 (0%)
    Social circumstances
    Social Stay Hospitalisation 0/71 (0%) 1/27 (3.7%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Vascular disorders
    Aortic Aneurysm 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Haematoma 1/71 (1.4%) 0/27 (0%) 0/115 (0%) 0/39 (0%) 0/45 (0%)
    Hypotension 1/71 (1.4%) 0/27 (0%) 4/115 (3.5%) 0/39 (0%) 0/45 (0%)
    Peripheral Ischaemia 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Thrombophlebitis 0/71 (0%) 0/27 (0%) 0/115 (0%) 1/39 (2.6%) 0/45 (0%)
    Venous Thrombosis 0/71 (0%) 0/27 (0%) 1/115 (0.9%) 0/39 (0%) 0/45 (0%)
    Other (Not Including Serious) Adverse Events
    Selinexor Approximately 55 mg/m^2 (60 to 120 mg Based on BSA) Selinexor 60mg (PV<5) (Equivalent to 35 mg/m^2) Selinexor 60mg (PV >=5) (Equivalent to 35 mg/m^2) Physician's Choice 1 (PV <5) Physician's Choice 2 (PV >=5)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 71/71 (100%) 27/27 (100%) 113/115 (98.3%) 37/39 (94.9%) 40/45 (88.9%)
    Blood and lymphatic system disorders
    Thrombocytopenia 29/71 (40.8%) 29 7/27 (25.9%) 7 38/115 (33%) 38 18/39 (46.2%) 18 11/45 (24.4%) 11
    Anaemia 20/71 (28.2%) 20 7/27 (25.9%) 7 29/115 (25.2%) 29 17/39 (43.6%) 17 10/45 (22.2%) 10
    Neutropenia 6/71 (8.5%) 6 5/27 (18.5%) 5 17/115 (14.8%) 17 10/39 (25.6%) 10 9/45 (20%) 9
    Leukopenia 2/71 (2.8%) 2 3/27 (11.1%) 3 10/115 (8.7%) 10 5/39 (12.8%) 5 4/45 (8.9%) 4
    Febrile Neutropenia 9/71 (12.7%) 9 2/27 (7.4%) 2 7/115 (6.1%) 7 3/39 (7.7%) 3 2/45 (4.4%) 2
    Leukocytosis 6/71 (8.5%) 6 2/27 (7.4%) 2 6/115 (5.2%) 6 4/39 (10.3%) 4 0/45 (0%) 0
    Lymphopenia 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 2/39 (5.1%) 2 1/45 (2.2%) 1
    Pancytopenia 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 2/39 (5.1%) 2 0/45 (0%) 0
    Coagulopathy 0/71 (0%) 0 1/27 (3.7%) 1 2/115 (1.7%) 2 1/39 (2.6%) 1 0/45 (0%) 0
    Lymphadenopathy 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 1/45 (2.2%) 1
    Increased Tendency To Bruise 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Polycythaemia 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Splenomegaly 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Thrombocytosis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Cardiac disorders
    Tachycardia 5/71 (7%) 5 1/27 (3.7%) 1 4/115 (3.5%) 4 0/39 (0%) 0 2/45 (4.4%) 2
    Sinus Tachycardia 4/71 (5.6%) 4 1/27 (3.7%) 1 2/115 (1.7%) 2 1/39 (2.6%) 1 0/45 (0%) 0
    Atrial Fibrillation 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 2/39 (5.1%) 2 1/45 (2.2%) 1
    Bradycardia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Acute Left Ventricular Failure 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Angina Pectoris 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Arrhythmia 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Bundle Branch Block Right 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Cardiac Failure 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Cardiac Flutter 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Extrasystoles 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Palpitations 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Sinus Bradycardia 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Supraventricular Tachycardia 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Tachycardia Paroxysmal 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Ear and labyrinth disorders
    Deafness 2/71 (2.8%) 2 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 1/45 (2.2%) 1
    Ear Discomfort 0/71 (0%) 0 2/27 (7.4%) 2 2/115 (1.7%) 2 0/39 (0%) 0 1/45 (2.2%) 1
    Vertigo 0/71 (0%) 0 0/27 (0%) 0 3/115 (2.6%) 3 0/39 (0%) 0 1/45 (2.2%) 1
    Ear Pain 2/71 (2.8%) 2 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Tinnitus 3/71 (4.2%) 3 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Ear Congestion 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Eustachian Tube Dysfunction 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Excessive Cerumen Production 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Hypoacusis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Endocrine disorders
    Hypothyroidism 0/71 (0%) 0 1/27 (3.7%) 1 4/115 (3.5%) 4 1/39 (2.6%) 1 0/45 (0%) 0
    Cushingoid 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Hyperthyroidism 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Eye disorders
    Vision Blurred 8/71 (11.3%) 8 1/27 (3.7%) 1 9/115 (7.8%) 9 1/39 (2.6%) 1 0/45 (0%) 0
    Visual Impairment 4/71 (5.6%) 4 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 1/45 (2.2%) 1
    Cataract 0/71 (0%) 0 1/27 (3.7%) 1 3/115 (2.6%) 3 0/39 (0%) 0 0/45 (0%) 0
    Dry Eye 1/71 (1.4%) 1 1/27 (3.7%) 1 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Visual Acuity Reduced 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 1/45 (2.2%) 1
    Conjunctival Haemorrhage 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 2/39 (5.1%) 2 0/45 (0%) 0
    Eye Pain 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Lacrimation Increased 1/71 (1.4%) 1 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Eye Haemorrhage 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Eyelid Oedema 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Ocular Hyperaemia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Periorbital Oedema 1/71 (1.4%) 1 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Photopsia 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Retinal Haemorrhage 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Diplopia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Eye Inflammation 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Eye Swelling 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Eyelid Ptosis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Vitreous Floaters 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Vitreous Haemorrhage 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Gastrointestinal disorders
    Nausea 41/71 (57.7%) 41 16/27 (59.3%) 16 68/115 (59.1%) 68 13/39 (33.3%) 13 8/45 (17.8%) 8
    Diarrhoea 17/71 (23.9%) 17 13/27 (48.1%) 13 41/115 (35.7%) 41 8/39 (20.5%) 8 6/45 (13.3%) 6
    Constipation 20/71 (28.2%) 20 8/27 (29.6%) 8 25/115 (21.7%) 25 16/39 (41%) 16 15/45 (33.3%) 15
    Vomiting 19/71 (26.8%) 19 10/27 (37%) 10 30/115 (26.1%) 30 7/39 (17.9%) 7 6/45 (13.3%) 6
    Stomatitis 8/71 (11.3%) 8 0/27 (0%) 0 8/115 (7%) 8 3/39 (7.7%) 3 3/45 (6.7%) 3
    Abdominal Pain 1/71 (1.4%) 1 0/27 (0%) 0 12/115 (10.4%) 12 2/39 (5.1%) 2 6/45 (13.3%) 6
    Abdominal Pain Upper 1/71 (1.4%) 1 1/27 (3.7%) 1 6/115 (5.2%) 6 1/39 (2.6%) 1 1/45 (2.2%) 1
    Dyspepsia 3/71 (4.2%) 3 2/27 (7.4%) 2 3/115 (2.6%) 3 1/39 (2.6%) 1 1/45 (2.2%) 1
    Gingival Bleeding 0/71 (0%) 0 0/27 (0%) 0 7/115 (6.1%) 7 1/39 (2.6%) 1 2/45 (4.4%) 2
    Haemorrhoids 1/71 (1.4%) 1 0/27 (0%) 0 3/115 (2.6%) 3 2/39 (5.1%) 2 3/45 (6.7%) 3
    Aphthous Ulcer 1/71 (1.4%) 1 1/27 (3.7%) 1 1/115 (0.9%) 1 2/39 (5.1%) 2 2/45 (4.4%) 2
    Mouth Haemorrhage 1/71 (1.4%) 1 1/27 (3.7%) 1 4/115 (3.5%) 4 1/39 (2.6%) 1 0/45 (0%) 0
    Abdominal Discomfort 0/71 (0%) 0 1/27 (3.7%) 1 1/115 (0.9%) 1 2/39 (5.1%) 2 2/45 (4.4%) 2
    Gingival Pain 1/71 (1.4%) 1 0/27 (0%) 0 3/115 (2.6%) 3 2/39 (5.1%) 2 0/45 (0%) 0
    Odynophagia 1/71 (1.4%) 1 1/27 (3.7%) 1 0/115 (0%) 0 2/39 (5.1%) 2 2/45 (4.4%) 2
    Toothache 2/71 (2.8%) 2 0/27 (0%) 0 3/115 (2.6%) 3 0/39 (0%) 0 1/45 (2.2%) 1
    Dry Mouth 2/71 (2.8%) 2 1/27 (3.7%) 1 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Gastrooesophageal Reflux Disease 3/71 (4.2%) 3 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Dysphagia 2/71 (2.8%) 2 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Flatulence 0/71 (0%) 0 0/27 (0%) 0 3/115 (2.6%) 3 1/39 (2.6%) 1 0/45 (0%) 0
    Melaena 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 2/45 (4.4%) 2
    Oral Pain 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 2/39 (5.1%) 2 0/45 (0%) 0
    Abdominal Pain Lower 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Anal Fissure 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Angina Bullosa Haemorrhagica 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 2/39 (5.1%) 2 0/45 (0%) 0
    Enterocolitis 0/71 (0%) 0 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Eructation 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Gastritis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Gastrointestinal Haemorrhage 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Mouth Ulceration 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Oral Disorder 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Oral Mucosa Haematoma 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Oral Mucosal Blistering 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Abdominal Tenderness 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Anal Incontinence 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Breath Odour 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Diverticulum 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Faeces Soft 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Gastrointestinal Pain 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Gingival Hypertrophy 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Glossitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Ileus 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Inguinal Hernia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Lip Blister 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Lip Dry 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Lip Oedema 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Lip Pain 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Lip Swelling 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Lip Ulceration 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Mouth Swelling 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Oesophagitis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Oral Contusion 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Oral Dysaesthesia 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Palatal Disorder 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Perianal Erythema 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Proctalgia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Rectal Fissure 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Rectal Haemorrhage 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Retching 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Salivary Hypersecretion 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Tongue Haematoma 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Tongue Ulceration 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Tooth Loss 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Trichoglossia 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    General disorders
    Fatigue 33/71 (46.5%) 33 13/27 (48.1%) 13 50/115 (43.5%) 50 15/39 (38.5%) 15 13/45 (28.9%) 13
    Pyrexia 8/71 (11.3%) 8 5/27 (18.5%) 5 28/115 (24.3%) 28 13/39 (33.3%) 13 13/45 (28.9%) 13
    Oedema Peripheral 17/71 (23.9%) 17 5/27 (18.5%) 5 21/115 (18.3%) 21 10/39 (25.6%) 10 5/45 (11.1%) 5
    Asthenia 17/71 (23.9%) 17 6/27 (22.2%) 6 22/115 (19.1%) 22 5/39 (12.8%) 5 5/45 (11.1%) 5
    Malaise 2/71 (2.8%) 2 1/27 (3.7%) 1 8/115 (7%) 8 3/39 (7.7%) 3 1/45 (2.2%) 1
    Oedema 2/71 (2.8%) 2 0/27 (0%) 0 5/115 (4.3%) 5 4/39 (10.3%) 4 2/45 (4.4%) 2
    Chills 1/71 (1.4%) 1 1/27 (3.7%) 1 5/115 (4.3%) 5 3/39 (7.7%) 3 1/45 (2.2%) 1
    Mucosal Inflammation 3/71 (4.2%) 3 0/27 (0%) 0 1/115 (0.9%) 1 4/39 (10.3%) 4 3/45 (6.7%) 3
    Pain 0/71 (0%) 0 0/27 (0%) 0 7/115 (6.1%) 7 1/39 (2.6%) 1 1/45 (2.2%) 1
    Gait Disturbance 2/71 (2.8%) 2 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    General Physical Health Deterioration 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Injection Site Bruising 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 1/45 (2.2%) 1
    Non-Cardiac Chest Pain 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Ulcer 2/71 (2.8%) 2 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Catheter Site Haemorrhage 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Face Oedema 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Generalised Oedema 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Secretion Discharge 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Catheter Site Haematoma 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Chest Pain 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Drug Intolerance 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Extravasation 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Feeling Cold 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Granuloma 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Hernia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Impaired Healing 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Infusion Site Haemorrhage 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Injection Site Discolouration 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Injection Site Pain 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Mucosal Dryness 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Nodule 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Peripheral Swelling 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Swelling 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Decreased Appetite 41/71 (57.7%) 41 12/27 (44.4%) 12 61/115 (53%) 61 9/39 (23.1%) 9 7/45 (15.6%) 7
    Hepatobiliary disorders
    Hyperbilirubinaemia 2/71 (2.8%) 2 0/27 (0%) 0 5/115 (4.3%) 5 1/39 (2.6%) 1 1/45 (2.2%) 1
    Cholelithiasis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Hepatomegaly 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Jaundice 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Ocular Icterus 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Immune system disorders
    Hypersensitivity 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Infections and infestations
    Urinary Tract Infection 6/71 (8.5%) 6 2/27 (7.4%) 2 9/115 (7.8%) 9 5/39 (12.8%) 5 2/45 (4.4%) 2
    Oral Herpes 2/71 (2.8%) 2 0/27 (0%) 0 3/115 (2.6%) 3 4/39 (10.3%) 4 4/45 (8.9%) 4
    Nasopharyngitis 1/71 (1.4%) 1 0/27 (0%) 0 5/115 (4.3%) 5 1/39 (2.6%) 1 3/45 (6.7%) 3
    Oral Candidiasis 4/71 (5.6%) 4 0/27 (0%) 0 4/115 (3.5%) 4 1/39 (2.6%) 1 1/45 (2.2%) 1
    Pneumonia 1/71 (1.4%) 1 0/27 (0%) 0 4/115 (3.5%) 4 3/39 (7.7%) 3 1/45 (2.2%) 1
    Cellulitis 2/71 (2.8%) 2 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 1/45 (2.2%) 1
    Lung Infection 2/71 (2.8%) 2 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Sinusitis 0/71 (0%) 0 1/27 (3.7%) 1 2/115 (1.7%) 2 2/39 (5.1%) 2 0/45 (0%) 0
    Upper Respiratory Tract Infection 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 1/45 (2.2%) 1
    Device Related Infection 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 0/45 (0%) 0
    Periodontitis 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 2/45 (4.4%) 2
    Pneumonia Fungal 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 3/45 (6.7%) 3
    Sepsis 1/71 (1.4%) 1 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Candida Infection 3/71 (4.2%) 3 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Folliculitis 0/71 (0%) 0 1/27 (3.7%) 1 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Oesophageal Candidiasis 0/71 (0%) 0 2/27 (7.4%) 2 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Skin Infection 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Staphylococcal Infection 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 2/45 (4.4%) 2
    Clostridium Difficile Colitis 0/71 (0%) 0 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Clostridium Difficile Infection 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Conjunctivitis 0/71 (0%) 0 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Ear Infection 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Fungal Infection 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Herpes Dermatitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Infection 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 1/45 (2.2%) 1
    Lip Infection 0/71 (0%) 0 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Nasal Herpes 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Pharyngitis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 2/39 (5.1%) 2 0/45 (0%) 0
    Pseudomonas Infection 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Rash Pustular 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Rhinovirus Infection 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Soft Tissue Infection 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Abscess Limb 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Acute Sinusitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Anal Abscess 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Aspergillus Infection 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Asymptomatic Bacteriuria 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Bacterial Infection 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Bacteriuria 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Bronchitis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Catheter Site Cellulitis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Clostridium Colitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Dermo-Hypodermitis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Diverticulitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Empyema 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Encephalitis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Enterobiasis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Enterococcal Infection 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Furuncle 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Genital Herpes 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Gingivitis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Groin Infection 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Herpes Simplex 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Herpes Zoster 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Infected Dermal Cyst 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Influenza 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Lower Respiratory Tract Infection 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Lymph Gland Infection 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Meningitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Metapneumovirus Infection 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Mucosal Infection 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Oesophageal Infection 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Ophthalmic Herpes Simplex 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Oral Fungal Infection 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Oral Infection 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Osteomyelitis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Parotitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Pneumonia Klebsiella 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Proteus Infection 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Pseudomembranous Colitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Respiratory Tract Infection 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Rhinitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Septic Shock 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Sialoadenitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Staphylococcal Bacteraemia 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Stenotrophomonas Infection 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Tonsillitis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Tonsillitis Bacterial 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Tooth Abscess 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Tooth Infection 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Varicella Zoster Virus Infection 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Hallucination 0/71 (0%) 0 0/27 (0%) 0 3/115 (2.6%) 3 0/39 (0%) 0 1/45 (2.2%) 1
    Personality Change 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Facial Bones Fracture 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Injury, poisoning and procedural complications
    Fall 6/71 (8.5%) 6 2/27 (7.4%) 2 9/115 (7.8%) 9 2/39 (5.1%) 2 2/45 (4.4%) 2
    Contusion 5/71 (7%) 5 2/27 (7.4%) 2 5/115 (4.3%) 5 3/39 (7.7%) 3 1/45 (2.2%) 1
    Infusion Related Reaction 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 1/45 (2.2%) 1
    Laceration 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 0/45 (0%) 0
    Procedural Pain 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Skin Abrasion 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Transfusion Reaction 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Allergic Transfusion Reaction 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Animal Bite 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Head Injury 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Joint Injury 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Overdose 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Periorbital Haematoma 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Post Procedural Contusion 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Post Procedural Haemorrhage 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Sunburn 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Tooth Fracture 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Wound 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Investigations
    Weight Decreased 15/71 (21.1%) 15 4/27 (14.8%) 4 20/115 (17.4%) 20 3/39 (7.7%) 3 3/45 (6.7%) 3
    Alanine Aminotransferase Increased 2/71 (2.8%) 2 2/27 (7.4%) 2 5/115 (4.3%) 5 2/39 (5.1%) 2 1/45 (2.2%) 1
    Aspartate Aminotransferase Increased 2/71 (2.8%) 2 0/27 (0%) 0 5/115 (4.3%) 5 2/39 (5.1%) 2 1/45 (2.2%) 1
    International Normalised Ratio Increased 1/71 (1.4%) 1 2/27 (7.4%) 2 4/115 (3.5%) 4 3/39 (7.7%) 3 0/45 (0%) 0
    Weight Increased 2/71 (2.8%) 2 1/27 (3.7%) 1 0/115 (0%) 0 6/39 (15.4%) 6 1/45 (2.2%) 1
    Blood Lactate Dehydrogenase Increased 5/71 (7%) 5 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Blood Alkaline Phosphatase Increased 2/71 (2.8%) 2 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 1/45 (2.2%) 1
    C-Reactive Protein Increased 1/71 (1.4%) 1 1/27 (3.7%) 1 2/115 (1.7%) 2 2/39 (5.1%) 2 0/45 (0%) 0
    Blood Uric Acid Increased 2/71 (2.8%) 2 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 0/45 (0%) 0
    Electrocardiogram Qt Prolonged 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 1/45 (2.2%) 1
    Activated Partial Thromboplastin Time Prolonged 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Blood Creatine Phosphokinase Increased 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Blood Thyroid Stimulating Hormone Increased 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    General Physical Condition Abnormal 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 2/45 (4.4%) 2
    Blood Creatine Phosphokinase Decreased 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Blood Pressure Decreased 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Blood Urea Increased 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Cardiac Murmur 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Ejection Fraction Decreased 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Electrocardiogram Change 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Hypophonesis 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Oxygen Saturation Decreased 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Transaminases Increased 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Alpha 1 Foetoprotein Increased 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Astrovirus Test Positive 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Bilirubin Urine 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Blast Cell Count Increased 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Bleeding Time Prolonged 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Blood Alkaline Phosphatase Decreased 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Blood Lactic Acid Increased 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Blood Test Abnormal 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Body Temperature Increased 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Gamma-Glutamyltransferase Increased 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Glomerular Filtration Rate Decreased 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Liver Function Test Increased 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Prothrombin Time Prolonged 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    White Blood Cell Count 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    White Blood Cell Count Increased 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Metabolism and nutrition disorders
    Hyponatraemia 26/71 (36.6%) 26 6/27 (22.2%) 6 25/115 (21.7%) 25 3/39 (7.7%) 3 1/45 (2.2%) 1
    Hypokalaemia 10/71 (14.1%) 10 1/27 (3.7%) 1 9/115 (7.8%) 9 5/39 (12.8%) 5 6/45 (13.3%) 6
    Hypocalcaemia 5/71 (7%) 5 2/27 (7.4%) 2 11/115 (9.6%) 11 2/39 (5.1%) 2 4/45 (8.9%) 4
    Hypercreatininaemia 5/71 (7%) 5 0/27 (0%) 0 13/115 (11.3%) 13 2/39 (5.1%) 2 1/45 (2.2%) 1
    Hypomagnesaemia 7/71 (9.9%) 7 0/27 (0%) 0 9/115 (7.8%) 9 2/39 (5.1%) 2 3/45 (6.7%) 3
    Hyperglycaemia 6/71 (8.5%) 6 3/27 (11.1%) 3 7/115 (6.1%) 7 1/39 (2.6%) 1 3/45 (6.7%) 3
    Hyperkalaemia 8/71 (11.3%) 8 2/27 (7.4%) 2 9/115 (7.8%) 9 1/39 (2.6%) 1 0/45 (0%) 0
    Dehydration 8/71 (11.3%) 8 0/27 (0%) 0 6/115 (5.2%) 6 3/39 (7.7%) 3 2/45 (4.4%) 2
    Hypophosphataemia 9/71 (12.7%) 9 1/27 (3.7%) 1 5/115 (4.3%) 5 0/39 (0%) 0 1/45 (2.2%) 1
    Hyperuricaemia 5/71 (7%) 5 1/27 (3.7%) 1 2/115 (1.7%) 2 1/39 (2.6%) 1 1/45 (2.2%) 1
    Hypoalbuminaemia 4/71 (5.6%) 4 1/27 (3.7%) 1 1/115 (0.9%) 1 2/39 (5.1%) 2 2/45 (4.4%) 2
    Hypercalcaemia 0/71 (0%) 0 0/27 (0%) 0 4/115 (3.5%) 4 1/39 (2.6%) 1 0/45 (0%) 0
    Hypermagnesaemia 3/71 (4.2%) 3 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Cachexia 0/71 (0%) 0 1/27 (3.7%) 1 3/115 (2.6%) 3 0/39 (0%) 0 0/45 (0%) 0
    Hyperlipasaemia 1/71 (1.4%) 1 0/27 (0%) 0 3/115 (2.6%) 3 0/39 (0%) 0 0/45 (0%) 0
    Hyperphosphataemia 0/71 (0%) 0 0/27 (0%) 0 3/115 (2.6%) 3 0/39 (0%) 0 1/45 (2.2%) 1
    Hypoglycaemia 3/71 (4.2%) 3 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Fluid Retention 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 1/45 (2.2%) 1
    Hyperamylasaemia 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Fluid Overload 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Tumour Lysis Syndrome 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Type 2 Diabetes Mellitus 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Diabetes Mellitus 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Failure To Thrive 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Gout 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Hyperglycaemic Hyperosmolar Nonketotic Syndrome 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Hyperhomocysteinaemia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Hypernatraemia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Hypouricaemia 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Metabolic Acidosis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Polydipsia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 5/71 (7%) 5 0/27 (0%) 0 6/115 (5.2%) 6 5/39 (12.8%) 5 1/45 (2.2%) 1
    Back Pain 0/71 (0%) 0 1/27 (3.7%) 1 6/115 (5.2%) 6 5/39 (12.8%) 5 5/45 (11.1%) 5
    Muscular Weakness 5/71 (7%) 5 0/27 (0%) 0 4/115 (3.5%) 4 3/39 (7.7%) 3 0/45 (0%) 0
    Pain In Extremity 4/71 (5.6%) 4 0/27 (0%) 0 3/115 (2.6%) 3 1/39 (2.6%) 1 2/45 (4.4%) 2
    Muscle Spasms 1/71 (1.4%) 1 2/27 (7.4%) 2 2/115 (1.7%) 2 1/39 (2.6%) 1 3/45 (6.7%) 3
    Bone Pain 0/71 (0%) 0 0/27 (0%) 0 5/115 (4.3%) 5 1/39 (2.6%) 1 0/45 (0%) 0
    Musculoskeletal Pain 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 2/39 (5.1%) 2 0/45 (0%) 0
    Myalgia 2/71 (2.8%) 2 0/27 (0%) 0 1/115 (0.9%) 1 2/39 (5.1%) 2 0/45 (0%) 0
    Neck Pain 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 2/45 (4.4%) 2
    Arthritis 0/71 (0%) 0 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Flank Pain 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 1/45 (2.2%) 1
    Hypercreatinaemia 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Joint Swelling 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Musculoskeletal Chest Pain 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 1/45 (2.2%) 1
    Pain In Jaw 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Bursitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Groin Pain 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Ligament Pain 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Limb Discomfort 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Limb Mass 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Muscle Mass 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Muscle Tightness 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Muscle Twitching 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Osteitis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Osteoarthritis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Spinal Osteoarthritis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Torticollis 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute Myeloid Leukaemia 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Basal Cell Carcinoma 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Chloroma 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Leukaemic Infiltration 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Uterine Leiomyoma 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Nervous system disorders
    Dysgeusia 7/71 (9.9%) 7 3/27 (11.1%) 3 12/115 (10.4%) 12 3/39 (7.7%) 3 2/45 (4.4%) 2
    Headache 5/71 (7%) 5 3/27 (11.1%) 3 3/115 (2.6%) 3 7/39 (17.9%) 7 6/45 (13.3%) 6
    Syncope 3/71 (4.2%) 3 1/27 (3.7%) 1 5/115 (4.3%) 5 2/39 (5.1%) 2 0/45 (0%) 0
    Dizziness 12/71 (16.9%) 12 2/27 (7.4%) 2 18/115 (15.7%) 18 8/39 (20.5%) 8 2/45 (4.4%) 2
    Presyncope 1/71 (1.4%) 1 3/27 (11.1%) 3 3/115 (2.6%) 3 0/39 (0%) 0 2/45 (4.4%) 2
    Somnolence 4/71 (5.6%) 4 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 0/45 (0%) 0
    Ageusia 1/71 (1.4%) 1 1/27 (3.7%) 1 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Balance Disorder 2/71 (2.8%) 2 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Memory Impairment 3/71 (4.2%) 3 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Ataxia 1/71 (1.4%) 1 1/27 (3.7%) 1 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Lethargy 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Polyneuropathy 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Tremor 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 0/45 (0%) 0
    Aphasia 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Cognitive Disorder 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Dysarthria 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Neuropathy Peripheral 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Paraesthesia 0/71 (0%) 0 2/27 (7.4%) 2 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Speech Disorder 1/71 (1.4%) 1 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Aphonia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Cogwheel Rigidity 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Coordination Abnormal 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Drooling 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Dysaesthesia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Encephalopathy 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Haemorrhage Intracranial 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Hemianopia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Hemianopia Homonymous 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Hypersomnia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Hypoaesthesia 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Hyposmia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Migraine 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Parosmia 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Peripheral Sensory Neuropathy 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Sensory Loss 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Synaesthesia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Psychiatric disorders
    Insomnia 10/71 (14.1%) 10 4/27 (14.8%) 4 7/115 (6.1%) 7 4/39 (10.3%) 4 3/45 (6.7%) 3
    Confusional State 5/71 (7%) 5 2/27 (7.4%) 2 8/115 (7%) 8 2/39 (5.1%) 2 3/45 (6.7%) 3
    Anxiety 2/71 (2.8%) 2 2/27 (7.4%) 2 4/115 (3.5%) 4 2/39 (5.1%) 2 1/45 (2.2%) 1
    Depression 2/71 (2.8%) 2 2/27 (7.4%) 2 2/115 (1.7%) 2 3/39 (7.7%) 3 1/45 (2.2%) 1
    Agitation 6/71 (8.5%) 6 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Restlessness 0/71 (0%) 0 2/27 (7.4%) 2 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Abnormal Dreams 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Bulimia Nervosa 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Delirium 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Disorientation 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Flat Affect 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Hallucination, Visual 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Irritability 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Listless 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Mental Disorder 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Mental Status Changes 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Nervousness 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Psychomotor Retardation 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Renal and urinary disorders
    Acute Kidney Injury 8/71 (11.3%) 8 2/27 (7.4%) 2 3/115 (2.6%) 3 2/39 (5.1%) 2 3/45 (6.7%) 3
    Haematuria 3/71 (4.2%) 3 3/27 (11.1%) 3 1/115 (0.9%) 1 2/39 (5.1%) 2 3/45 (6.7%) 3
    Pollakiuria 2/71 (2.8%) 2 0/27 (0%) 0 3/115 (2.6%) 3 1/39 (2.6%) 1 2/45 (4.4%) 2
    Proteinuria 3/71 (4.2%) 3 1/27 (3.7%) 1 1/115 (0.9%) 1 2/39 (5.1%) 2 1/45 (2.2%) 1
    Dysuria 1/71 (1.4%) 1 1/27 (3.7%) 1 2/115 (1.7%) 2 0/39 (0%) 0 2/45 (4.4%) 2
    Renal Failure 2/71 (2.8%) 2 1/27 (3.7%) 1 1/115 (0.9%) 1 1/39 (2.6%) 1 1/45 (2.2%) 1
    Urinary Incontinence 2/71 (2.8%) 2 1/27 (3.7%) 1 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Urinary Retention 0/71 (0%) 0 1/27 (3.7%) 1 2/115 (1.7%) 2 1/39 (2.6%) 1 0/45 (0%) 0
    Bladder Dilatation 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Chronic Kidney Disease 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Micturition Urgency 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Bladder Pain 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Chromaturia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Incontinence 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Nocturia 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Polyuria 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Urethral Caruncle 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Urethral Haemorrhage 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Urge Incontinence 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Urinary Tract Obstruction 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Urinary Tract Pain 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Reproductive system and breast disorders
    Breast Pain 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Breast Swelling 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Gynaecomastia 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Nipple Pain 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Oedema Genital 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Ovarian Cyst 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Testicular Oedema 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Vaginal Haemorrhage 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 14/71 (19.7%) 14 5/27 (18.5%) 5 24/115 (20.9%) 24 8/39 (20.5%) 8 10/45 (22.2%) 10
    Epistaxis 13/71 (18.3%) 13 3/27 (11.1%) 3 25/115 (21.7%) 25 7/39 (17.9%) 7 7/45 (15.6%) 7
    Cough 12/71 (16.9%) 12 3/27 (11.1%) 3 15/115 (13%) 15 5/39 (12.8%) 5 8/45 (17.8%) 8
    Oropharyngeal Pain 3/71 (4.2%) 3 2/27 (7.4%) 2 3/115 (2.6%) 3 2/39 (5.1%) 2 3/45 (6.7%) 3
    Productive Cough 4/71 (5.6%) 4 0/27 (0%) 0 3/115 (2.6%) 0 3/39 (7.7%) 3 1/45 (2.2%) 1
    Haemoptysis 2/71 (2.8%) 2 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 3/45 (6.7%) 3
    Dyspnoea Exertional 1/71 (1.4%) 1 0/27 (0%) 0 4/115 (3.5%) 4 1/39 (2.6%) 1 1/45 (2.2%) 1
    Nasal Congestion 1/71 (1.4%) 1 1/27 (3.7%) 1 4/115 (3.5%) 4 0/39 (0%) 0 1/45 (2.2%) 1
    Pleural Effusion 1/71 (1.4%) 1 2/27 (7.4%) 2 2/115 (1.7%) 2 2/39 (5.1%) 2 0/45 (0%) 0
    Hypoxia 2/71 (2.8%) 2 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 2/45 (4.4%) 2
    Rhinorrhoea 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 2/45 (4.4%) 2
    Wheezing 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 2/45 (4.4%) 2
    Atelectasis 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Hiccups 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 0/45 (0%) 0
    Pleuritic Pain 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 1/45 (2.2%) 1
    Respiratory Failure 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 1/45 (2.2%) 1
    Pulmonary Oedema 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Sinus Congestion 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Sinus Pain 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Upper-Airway Cough Syndrome 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 1/45 (2.2%) 1
    Chronic Obstructive Pulmonary Disease 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Dysphonia 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Laryngeal Pain 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Lung Consolidation 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Lung Infiltration 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Nasal Dryness 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Nasal Inflammation 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Paranasal Sinus Discomfort 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Pharyngeal Inflammation 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Pneumonitis 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Pulmonary Mass 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Rales 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Respiratory Tract Congestion 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Rhinitis Allergic 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Rhonchi 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Sinus Disorder 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Tachypnoea 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Tonsillar Erythema 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Tonsillar Hypertrophy 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Skin and subcutaneous tissue disorders
    Night Sweats 8/71 (11.3%) 8 3/27 (11.1%) 3 10/115 (8.7%) 10 1/39 (2.6%) 1 4/45 (8.9%) 4
    Petechiae 4/71 (5.6%) 4 0/27 (0%) 0 3/115 (2.6%) 3 7/39 (17.9%) 7 6/45 (13.3%) 6
    Hyperhidrosis 6/71 (8.5%) 6 0/27 (0%) 0 3/115 (2.6%) 3 1/39 (2.6%) 1 1/45 (2.2%) 1
    Rash 2/71 (2.8%) 2 1/27 (3.7%) 1 1/115 (0.9%) 1 4/39 (10.3%) 4 2/45 (4.4%) 2
    Rash Maculo-Papular 1/71 (1.4%) 1 0/27 (0%) 0 3/115 (2.6%) 3 2/39 (5.1%) 2 2/45 (4.4%) 2
    Ecchymosis 3/71 (4.2%) 3 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 2/45 (4.4%) 2
    Pruritus 1/71 (1.4%) 1 1/27 (3.7%) 1 2/115 (1.7%) 2 2/39 (5.1%) 2 1/45 (2.2%) 1
    Skin Lesion 3/71 (4.2%) 3 0/27 (0%) 0 1/115 (0.9%) 1 2/39 (5.1%) 2 0/45 (0%) 0
    Skin Ulcer 1/71 (1.4%) 1 1/27 (3.7%) 1 2/115 (1.7%) 2 0/39 (0%) 0 1/45 (2.2%) 1
    Alopecia 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 1/39 (2.6%) 1 0/45 (0%) 0
    Decubitus Ulcer 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 2/39 (5.1%) 2 0/45 (0%) 0
    Erythema 0/71 (0%) 0 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 2/45 (4.4%) 2
    Cold Sweat 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 2/39 (5.1%) 2 0/45 (0%) 0
    Dermatitis 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Purpura 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 1/39 (2.6%) 1 0/45 (0%) 0
    Skin Mass 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 1/45 (2.2%) 1
    Swelling Face 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Dermal Cyst 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Dermatitis Acneiform 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Dermatitis Bullous 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Dry Skin 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Facial Wasting 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Macule 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Miliaria 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Nail Disorder 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Photosensitivity Reaction 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Rash Erythematous 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Rash Pruritic 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Skin Discolouration 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Skin Hyperpigmentation 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Skin Induration 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Skin Maceration 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Urticaria 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Vascular disorders
    Hypotension 6/71 (8.5%) 6 1/27 (3.7%) 1 11/115 (9.6%) 11 4/39 (10.3%) 4 1/45 (2.2%) 1
    Haematoma 0/71 (0%) 0 2/27 (7.4%) 2 5/115 (4.3%) 5 7/39 (17.9%) 7 1/45 (2.2%) 1
    Hypertension 4/71 (5.6%) 4 2/27 (7.4%) 2 2/115 (1.7%) 2 1/39 (2.6%) 1 1/45 (2.2%) 1
    Pallor 1/71 (1.4%) 1 0/27 (0%) 0 3/115 (2.6%) 3 2/39 (5.1%) 2 1/45 (2.2%) 1
    Haemorrhage 1/71 (1.4%) 1 0/27 (0%) 0 2/115 (1.7%) 2 0/39 (0%) 0 1/45 (2.2%) 1
    Phlebitis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 3/39 (7.7%) 3 0/45 (0%) 0
    Thrombophlebitis 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 1/45 (2.2%) 1
    Orthostatic Hypotension 2/71 (2.8%) 2 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Deep Vein Thrombosis 2/71 (2.8%) 2 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Flushing 1/71 (1.4%) 1 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Circulatory Collapse 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Embolism 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Hot Flush 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 1/39 (2.6%) 1 0/45 (0%) 0
    Intermittent Claudication 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0
    Lymphoedema 0/71 (0%) 0 1/27 (3.7%) 1 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Poor Peripheral Circulation 1/71 (1.4%) 1 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 0/45 (0%) 0
    Thrombophlebitis Superficial 0/71 (0%) 0 0/27 (0%) 0 0/115 (0%) 0 0/39 (0%) 0 1/45 (2.2%) 1
    Venous Thrombosis 0/71 (0%) 0 0/27 (0%) 0 1/115 (0.9%) 1 0/39 (0%) 0 0/45 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Results Point of Contact

    Name/Title Jatin Shah, MD
    Organization Karyopharm Therapeutics Inc.
    Phone (617) 658-0600
    Email jshah@karyopharm.com
    Responsible Party:
    Karyopharm Therapeutics Inc
    ClinicalTrials.gov Identifier:
    NCT02088541
    Other Study ID Numbers:
    • KCP-330-008
    First Posted:
    Mar 17, 2014
    Last Update Posted:
    Oct 8, 2020
    Last Verified:
    Sep 1, 2020