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Safety and Tolerability Study of Voreloxin and Cytarabine Combination in Acute Myeloid Leukemia in Humans

Sponsor
Sunesis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00541866
Collaborator
(none)
110
Enrollment
9
Locations
1
Arm
52.3
Actual Duration (Months)
12.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety and tolerability of voreloxin (vosaroxin) injection in combination with cytarabine in patients with relapsed or refractory acute myeloid leukemia.

Condition or Disease Intervention/Treatment Phase
  • Drug: Voreloxin injection and cytarabine
 Phase 1/Phase 2

Detailed Description

An open-label, Phase 1b/2 study using a dose-escalation design with expansion at the maximum tolerated dose (MTD) using 2 dosing schedules:

During the Schedule A dose-escalation phase, patients with relapsed or refractory acute myeloid leukemia (AML) enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dosing regimen of vosaroxin of 10 mg/m2 on Days 1 and 4 of each cycle in combination with a 24-hour continuous intravenous (CIV) infusion of cytarabine 400 mg/m2/day × 5 days. If none of the 3 patients or 1 of 6 patients experience a dose-limiting toxicity (DLT) at the vosaroxin starting dose, dose-escalate vosaroxin. If 2 of 6 patients experienced a DLT at the vosaroxin starting dose, reduce the dose of cytarabine to reduced to 200 mg/m2 (only case in which the cytarabine could have been reduced). The vosaroxin dose escalated following a modified Fibonacci schema.

For Schedule B dose-escalation phase, patients with relapsed or refractory AML enrolled in cohorts of at least 3 patients to identify the MTD. Begin with a starting dose regimen of vosaroxin of 70 mg/m2 on Days 1 and 4 in combination with cytarabine as a 2-hour infusion of 1 g/m2/day × 5 days. No reductions of cytarabine allowed in Schedule B. If none of the 3 patients or 1 of 6 patients experienced a DLT in the first cohort of Schedule B, escalate the dose of vosaroxin. If DLTs occurred in 2 of 6 patients during the starting dose, reduce the vosaroxin dose to 50 mg/m2.

For both Schedules, the highest dose at which fewer than 2 of 6 patients experienced a DLT during induction became the MTD and the recommended future dose.

Once the MTD of vosaroxin was determined for Schedule A, first relapse patients were enrolled in the expansion phase at that dose level to obtain additional safety and efficacy information. When the MTD of vosaroxin was determined for Schedule B, first relapse patients and patients with primary refractory disease were enrolled in the expansion phase at that dose level to characterize the safety and efficacy profile in this population.

Study Design

Study Type:
Interventional
Actual Enrollment :
110 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b/2, Open-Label, Multicenter, Dose-Escalating, Clinical Study of the Safety, Tolerability, and PK and PD Profiles of Voreloxin Injection in Combination With Cytarabine in Patients With Relapsed or Refractory AML
Actual Study Start Date :
Oct 6, 2007
Actual Primary Completion Date :
Feb 15, 2012
Actual Study Completion Date :
Feb 15, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: Voreloxin injection and cytarabine

Dose-escalation Phase Schedule A: Schedule B: Expansion Phase Schedule A: Schedule B:

Drug: Voreloxin injection and cytarabine
Dose-escalation Phase Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Expansion Phase The MTD determined in the dose-escalation phase was used in the expansion phase. Schedule A: 80 mg/m2 vosaroxin on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion at 400 mg/m2/day × 5 days) Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)
Other Names:
  • ARA-C, Cytosar-U

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Incidence of Dose-Limiting Toxicity (DLT) to Determine Maximum Tolerated Dose in Schedule A and Schedule B of Dose Escalation Phase (Group 1 and Group 2) [From start of treatment (Day 1) through Induction Day 29 or the start of reinduction, whichever occurred first.]

      Patients were treated in cohorts with escalating doses of vosaroxin administered in combination with cytarabine in Schedule A, and with vosaroxin in escalating doses in Schedule B. For both Schedules, the highest dose at which fewer than 2 of 6 (<0.33) patients experienced a dose-limiting toxicity (DLT) during induction became the MTD and the recommended future dose.

    Secondary Outcome Measures

    1. Remission Rates (CR+CRp) [Monthly after the end of treatment for the first year, then every 2 months thereafter for upto 2 years]

      Complete remission (CR) plus CR with incomplete platelet recovery (CRp) per The IWG criteria for remission modified by Sunesis, assessed by investigator. CR is defined as >1000 Neutrophils (ul), >100,000 Platelets (uL) and <5 BM Blasts (%); CRp is defined as >1000 Neutrophils (ul), <=100,000 Platelets (uL) and <5 BM Blasts (%); CRi is defined as >1000 Neutrophils (ul), <100,000 Platelets (uL) and <5 BM Blasts (%); Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (CR with morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.

    2. Leukemia-free Survival (LFS) [From time of the start of CR or CRp to the earliest date of relapse, commencement of reinduction therapy, or death, assessed monthly up to 2 years after the end of study visit.]

      Leukemia-free survival is censored at the last known alive date without report of relapse.

    3. Overall Survival [Time between the date of first study treatment and the date of death due to any cause for upto 2 years after the end of study visit]

      Overall survival is censored at the earlier of the cutoff date for analysis and the last date known to be alive for patients not known to have died.

    4. All Cause Mortality [30 and 60 days]

      Mortality of those patients enrolled in the study and receiving intervention

    Eligibility Criteria

    Criteria

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

    KEY INCLUSION CRITERIA

    1. Relapsed or refractory AML subtypes defined by WHO, except acute promyelocytic leukemia. Relapsed/refractory disease may be de novo AML or secondary AML

    2. Treated with one to threee induction/reinduction AML regimens, prior induction or consolidation therapy with cytarabine allowed

    3. At least 10% blasts by BM biopsy or aspirate

    4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

    5. Clinical laboratory values of a) Serum creatinine ≤1.5 mg/dL and calculated or measured creatinine clearance (CRcl) of ≥50 mL/min, b) Total bilirubin ≤1.5 X upper limit of normal and c) Aspartate aminotransferase (AST) or alkaline phosphatase ≤2.5 X ULN.

    KEY EXCLUSION CRITERIA

    Patients with:

    1. Allogenic bone marrow transplant/stem cell transplant

    2. Persistent, clinically significant, chronic toxicities from prior AML therapy that would contraindicate the patient's participation in the clinical study due to safety concerns or compliance with study procedures

    3. Acute promyelocytic leukemia

    4. Disseminated intravascular coagulation

    5. Active infections, unless adequately treated with antibiotic, antiviral, or antifungal agents within in 7 days before Induction Day 1

    6. Active central nervous system involvement by AML

    7. Other active malignancies or other malignancies within the last 12 months except nonmelanoma skin cancer or cervical intraepithelial neoplasia

    8. A requirement for hemodialysis or peritoneal dialysis

    9. A history of myocardial infarction within the 3 months before treatment with vosaroxin

    10. A history of cerebrovascular accident/transient ischemic attack within the 3 months before treatment with vosaroxin

    11. A thromboembolic event (deep vein thrombosis or pulmonary embolus) within 28 days before treatment with vosaroxin

    12. Investigational products taken within 28 days before treatment with vosaroxin, and non-investigational cancer therapies or radiation therapy within 14 days before treatment with vosaroxin, with the exception of hydroxyurea.

    13. A known intolerance to cytarabine or known allergy to D-sorbitol or methanesulfonic acid (excipients used in vosaroxin)

    14. Prior exposure to vosaroxin

    15. Any other medical, psychological, or social condition that contraindicates their participation in the clinical study due to safety concerns or compliance with study procedures in the opinion of the Investigator,or Sunesis Medical Monitor

    In addition:

    1. Women who are pregnant or breastfeeding

    2. Women who are of childbearing potential or male patients who had partners of childbearing potential who were unwilling to use an approved, effective means of contraception according to the study site's standards

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 HealthOne Presbyterian/St. Luke's Medical Center Denver Colorado United States 80218
    2 Rocky Mountain Cancer Centers Denver Colorado United States 80218
    3 H. Lee Moffitt Cancer Center Tampa Florida United States 33612
    4 Northwestern Medical Faculty Foundation Chicago Illinois United States 60611
    5 Northwestern Memorial Hospital Chicago Illinois United States 60611
    6 Indiana University Cancer Center Indianapolis Indiana United States 46206
    7 Johns Hopkins University - Sidney Kimmel Cancer Center Baltimore Maryland United States 21205
    8 New York Presbyterian Hospital-Weill Cornell Medical College New York New York United States 10065
    9 MD Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • Sunesis Pharmaceuticals

    Investigators

    • Study Director: Sunesis Medical Monitor, MD, Sunesis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sunesis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00541866
    Other Study ID Numbers:
    • SPO-0012
    First Posted:
    Oct 10, 2007
    Last Update Posted:
    Jan 9, 2018
    Last Verified:
    Dec 1, 2017
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Sunesis Pharmaceuticals
    Leukemia
    Acute Myeloid
    Relapsed
    Refractory
    Cancer
    AML
    Cytarabine
    SNS-595
    Phase 1
    Voreloxin
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Myeloid
    Leukemia, Myeloid, Acute
    Cytarabine

    Study Results

    Participant Flow

    Recruitment Details Conducted in 7 centers in the USA between 2007 and 2010
    Pre-assignment Detail Dose-escalation phase Group 1 (Sch A, 10 to 90 mg/m2): 41 patients (39 treated) Group 2 (Sch B, 70 to 90 mg/m2): 18 patients Dose-expansion phase Group 3 (Sch A first relapse, 80 mg/m2): 17 patients Group 4 (Sch B first relapse, 90 mg/m2): 16 patients Group 5 (Sch B primary refractory, 90 mg/m2): 18 patients Total: 110. Treated: 108
    Arm/Group Title Group 1 (Sch A, 10 to 90 mg/m2) Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2) Group 4 (Sch B, First Relapse, 90 mg/m2) Group 5 (Sch B, Primary Refractory, 90 mg/m2)
    Arm/Group Description Dose Escalation Phase Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Dose Escalation Phase Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Expansion Phase: Schedule A: 80 mg/m2 vosaroxin on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion at 400 mg/m2/day × 5 days) Expansion Phase: Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days) Expansion Phase Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)
    Period Title: Overall Study
    STARTED 41 18 17 16 18
    COMPLETED 7 0 2 0 3
    NOT COMPLETED 34 18 15 16 15

    Baseline Characteristics

    Arm/Group Title Group 1 (Sch A, 10 to 90 mg/m2) Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2): Group 4 (Sch B, First Relapse, 90 mg/m2) Group 5 (Sch B, Primary Refractory, 90 mg/m2): Total
    Arm/Group Description Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Total of all reporting groups
    Overall Participants 39 18 17 16 18 108
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    58.0
    (10.90)
    47.4
    (13.83)
    59.7
    (9.29)
    58.4
    (11.03)
    56.3
    (12.09)
    56.3
    (11.95)
    Sex: Female, Male (Count of Participants)
    Female
    11
    28.2%
    5
    27.8%
    6
    35.3%
    6
    37.5%
    8
    44.4%
    36
    33.3%
    Male
    28
    71.8%
    13
    72.2%
    11
    64.7%
    10
    62.5%
    10
    55.6%
    72
    66.7%
    Region of Enrollment (participants) [Number]
    United States
    39
    100%
    18
    100%
    17
    100%
    16
    100%
    18
    100%
    108
    100%

    Outcome Measures

    1. Primary Outcome
    Title Incidence of Dose-Limiting Toxicity (DLT) to Determine Maximum Tolerated Dose in Schedule A and Schedule B of Dose Escalation Phase (Group 1 and Group 2)
    Description Patients were treated in cohorts with escalating doses of vosaroxin administered in combination with cytarabine in Schedule A, and with vosaroxin in escalating doses in Schedule B. For both Schedules, the highest dose at which fewer than 2 of 6 (<0.33) patients experienced a dose-limiting toxicity (DLT) during induction became the MTD and the recommended future dose.
    Time Frame From start of treatment (Day 1) through Induction Day 29 or the start of reinduction, whichever occurred first.

    Outcome Measure Data

    Analysis Population Description
    Patients experiencing a dose-limiting toxicity (DLT) during induction when treated with escalating doses of vosaroxin administered in combination with cytarabine on Days 1 and 4 in Schedule A, and with vosaroxin in escalating doses administered on Days 1 and 4 in Schedule B.
    Arm/Group Title Sch A, Cohort 10mg/m2 Sch A, Cohort 20mg/m2 SchA, Cohort 34mg/m2 Sch A, Cohort 50mg/m2 Sch A, Cohort 70mg/m2 Sch A, Cohort 80mg/m2 Sch A, Cohort 90mg/m2 Sch B, Cohort 70 mg/m2 Sch B, Cohort 80mg/m2 Sch B, Cohort 90mg/m2
    Arm/Group Description Vosaroxin injection 10 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Vosaroxin injection 20 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Vosaroxin injection 34 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Vosaroxin injection 50 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Vosaroxin injection 70 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Vosaroxin injection 80 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Vosaroxin injection 90 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection 70 mg/m2 on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days). Vosaroxin injection 80 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Vosaroxin injection 90 mg/m2 on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days)
    Measure Participants 4 3 4 6 7 8 7 6 6 6
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5.6%
    1
    0.9%
    2
    NaN
    0
    NaN
    1
    NaN
    1
    NaN
    2. Secondary Outcome
    Title Remission Rates (CR+CRp)
    Description Complete remission (CR) plus CR with incomplete platelet recovery (CRp) per The IWG criteria for remission modified by Sunesis, assessed by investigator. CR is defined as >1000 Neutrophils (ul), >100,000 Platelets (uL) and <5 BM Blasts (%); CRp is defined as >1000 Neutrophils (ul), <=100,000 Platelets (uL) and <5 BM Blasts (%); CRi is defined as >1000 Neutrophils (ul), <100,000 Platelets (uL) and <5 BM Blasts (%); Investigators were to determine a response category for each patient by examination of bone marrow and blood counts at the time of hematologic recovery after induction or reinduction. Investigator assessment categories included CR, CRp, CRi (CR with morphologic CR with incomplete blood count recovery), PR (partial remission), treatment failure, and relapse.
    Time Frame Monthly after the end of treatment for the first year, then every 2 months thereafter for upto 2 years

    Outcome Measure Data

    Analysis Population Description
    All treated set which includes all enrolled patients who received any IMP.
    Arm/Group Title Group 1 (Sch A, 10 to 90 mg/m2) Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2): Group 4 (Sch B, First Relapse, 90 mg/m2) Group 5 (Sch B, Primary Refractory, 90 mg/m2): Total
    Arm/Group Description Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) 5 groups combined
    Measure Participants 39 18 17 16 18 108
    Count of Participants [Participants]
    9
    23.1%
    4
    22.2%
    7
    41.2%
    3
    18.8%
    4
    22.2%
    27
    25%
    3. Secondary Outcome
    Title Leukemia-free Survival (LFS)
    Description Leukemia-free survival is censored at the last known alive date without report of relapse.
    Time Frame From time of the start of CR or CRp to the earliest date of relapse, commencement of reinduction therapy, or death, assessed monthly up to 2 years after the end of study visit.

    Outcome Measure Data

    Analysis Population Description
    All treated analysis set.
    Arm/Group Title Group 1 (Sch A, 10 to 90 mg/m2) Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2): Group 4 (Sch B, First Relapse, 90 mg/m2) Group 5 (Sch B, Primary Refractory, 90 mg/m2):
    Arm/Group Description Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days)
    Measure Participants 39 18 17 16 18
    Median (95% Confidence Interval) [months]
    12.0
    4.7
    7.4
    25.2
    NA
    4. Secondary Outcome
    Title Overall Survival
    Description Overall survival is censored at the earlier of the cutoff date for analysis and the last date known to be alive for patients not known to have died.
    Time Frame Time between the date of first study treatment and the date of death due to any cause for upto 2 years after the end of study visit

    Outcome Measure Data

    Analysis Population Description
    All treated analysis set
    Arm/Group Title Group 1 (Sch A, 10 to 90 mg/m2) Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2): Group 4 (Sch B, First Relapse, 90 mg/m2) Group 5 (Sch B, Primary Refractory, 90 mg/m2):
    Arm/Group Description Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days)
    Measure Participants 39 18 17 16 18
    Median (95% Confidence Interval) [months]
    4.1
    8.0
    4.1
    7.1
    5.9
    5. Secondary Outcome
    Title All Cause Mortality
    Description Mortality of those patients enrolled in the study and receiving intervention
    Time Frame 30 and 60 days

    Outcome Measure Data

    Analysis Population Description
    All treated analysis set
    Arm/Group Title Group 1 (Sch A, 10 to 90 mg/m2) Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2) Group 4 (Sch B, First Relapse, 90 mg/m2) Group 5 (Sch B, Primary Refractory, 90 mg/m2)
    Arm/Group Description Dose Escalation Phase Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Dose Escalation Phase Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Expansion Phase: Schedule A: 80 mg/m2 vosaroxin on Days 1 and 4 in combination with cytarabine (24-hour CIV infusion at 400 mg/m2/day × 5 days) Expansion Phase: Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days) Expansion Phase Schedule B: 90 mg/m2 vosaroxin (dose-escalation) on Days 1 and 4 in combination with cytarabine (2 hour IV infusion at 1 g/m2/day × 5 days)
    Measure Participants 39 18 17 16 18
    30 Days
    8
    20.5%
    0
    0%
    1
    5.9%
    0
    0%
    1
    5.6%
    60 Days
    10
    25.6%
    2
    11.1%
    2
    11.8%
    1
    6.3%
    1
    5.6%

    Adverse Events

    Time Frame 4 years, 4 months
    Adverse Event Reporting Description
    Arm/Group Title Group 1 (Sch A, 10 to 90 mg/m2): Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2) Group 4 (Sch B, First Relapse, 90 mg/m2): Group 5 (Sch B, Primary Refractory, 90 mg/m2):
    Arm/Group Description Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) saroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule A: vosaroxin injection (dose-escalation from 10 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (24-hour continuous IV [CIV] infusion of 400 mg/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days) Schedule B: vosaroxin injection (dose-escalation from 70 to 90 mg/m2) on Days 1 and 4 in combination with cytarabine (2-hour intravenous [IV] infusion of 1 g/m2/day × 5 days)
    All Cause Mortality
    Group 1 (Sch A, 10 to 90 mg/m2): Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2) Group 4 (Sch B, First Relapse, 90 mg/m2): Group 5 (Sch B, Primary Refractory, 90 mg/m2):
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 36/39 (92.3%) 16/18 (88.9%) 15/17 (88.2%) 14/16 (87.5%) 13/18 (72.2%)
    Serious Adverse Events
    Group 1 (Sch A, 10 to 90 mg/m2): Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2) Group 4 (Sch B, First Relapse, 90 mg/m2): Group 5 (Sch B, Primary Refractory, 90 mg/m2):
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 20/39 (51.3%) 7/18 (38.9%) 9/17 (52.9%) 3/16 (18.8%) 11/18 (61.1%)
    Blood and lymphatic system disorders
    Febrile neutropenia 4/39 (10.3%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 4/18 (22.2%)
    Leukocytosis 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Cardiac disorders
    Arrhythmia 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Cardiac arrest 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Cardiac failure 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Left ventricular dysfunction 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Gastrointestinal disorders
    Colitis 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Diarrhoea 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Gastrointestinal haemorrhage 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Large intestinal obstruction 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Lower gastrointestinal haemorrhage 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Nausea 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Oesophagitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Oral soft tissue disorder 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Stomatitis 2/39 (5.1%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Vomiting 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    General disorders
    Multi-organ failure 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Hepatobiliary disorders
    Acute hepatic failure 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Immune system disorders
    Hypersensitivity 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Infections and infestations
    Bacteraemia 2/39 (5.1%) 1/18 (5.6%) 1/17 (5.9%) 1/16 (6.3%) 1/18 (5.6%)
    Cellulitis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Chronic sinusitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Clostridium difficile colitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Enterobacter bacteraemia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Enterococcal bacteraemia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Enterococcal sepsis 1/39 (2.6%) 0/18 (0%) 2/17 (11.8%) 0/16 (0%) 0/18 (0%)
    Escherichia bacteraemia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pneumonia 2/39 (5.1%) 2/18 (11.1%) 2/17 (11.8%) 0/16 (0%) 1/18 (5.6%)
    Pneumonia fungal 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pseudomonal bacteraemia 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Sepsis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 3/18 (16.7%)
    Septic shock 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Staphylococcal bacteraemia 2/39 (5.1%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Streptococcal bacteraemia 2/39 (5.1%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Streptococcal sepsis 0/39 (0%) 0/18 (0%) 0/17 (0%) 2/16 (12.5%) 0/18 (0%)
    Upper respiratory tract infection 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Urosepsis 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Metabolism and nutrition disorders
    Failure to thrive 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Nervous system disorders
    Grand mal convulsion 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Migraine 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Peripheral motor neuropathy 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Syncope 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Renal and urinary disorders
    Renal failure acute 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Cough 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hypoxia 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Interstitial lung disease 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Pulmonary alveolar haemorrhage 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Pulmonary haemorrhage 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Skin and subcutaneous tissue disorders
    Photosensitivity reaction 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Vascular disorders
    Deep vein thrombosis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hypertensive crisis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Other (Not Including Serious) Adverse Events
    Group 1 (Sch A, 10 to 90 mg/m2): Group 2 (Sch B, 70 to 90 mg/m2): Group 3 (Sch A, First Relapse, 80 mg/m2) Group 4 (Sch B, First Relapse, 90 mg/m2): Group 5 (Sch B, Primary Refractory, 90 mg/m2):
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 39/39 (100%) 18/18 (100%) 17/17 (100%) 16/16 (100%) 18/18 (100%)
    Blood and lymphatic system disorders
    Anaemia 19/39 (48.7%) 11/18 (61.1%) 8/17 (47.1%) 11/16 (68.8%) 6/18 (33.3%)
    Coagulopathy 1/39 (2.6%) 1/18 (5.6%) 1/17 (5.9%) 3/16 (18.8%) 2/18 (11.1%)
    Febrile neutropenia 21/39 (53.8%) 12/18 (66.7%) 8/17 (47.1%) 10/16 (62.5%) 8/18 (44.4%)
    Hypocoagulable state 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Leukopenia 2/39 (5.1%) 3/18 (16.7%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Lymphadenopathy 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Neutropenia 6/39 (15.4%) 4/18 (22.2%) 2/17 (11.8%) 6/16 (37.5%) 5/18 (27.8%)
    Retroperitoneal lymphadenopathy 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Splenic infarction 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Splenic lesion 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Splenomegaly 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Thrombocytopenia 17/39 (43.6%) 9/18 (50%) 7/17 (41.2%) 9/16 (56.3%) 8/18 (44.4%)
    Cardiac disorders
    Arrhythmia supraventricular 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Arteriosclerosis coronary artery 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Atrial fibrillation 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Atrial flutter 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Atrial tachycardia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Bradycardia 7/39 (17.9%) 0/18 (0%) 2/17 (11.8%) 1/16 (6.3%) 2/18 (11.1%)
    Cardiac failure congestive 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Intracardiac mass 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Left ventricular dysfunction 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Left ventricular hypertrophy 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Mitral valve incompetence 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Palpitations 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Pericardial effusion 1/39 (2.6%) 2/18 (11.1%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Sinus bradycardia 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Sinus tachycardia 2/39 (5.1%) 0/18 (0%) 2/17 (11.8%) 1/16 (6.3%) 0/18 (0%)
    Supraventricular extrasystoles 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Supraventricular tachycardia 1/39 (2.6%) 0/18 (0%) 2/17 (11.8%) 0/16 (0%) 0/18 (0%)
    Tachycardia 11/39 (28.2%) 6/18 (33.3%) 4/17 (23.5%) 3/16 (18.8%) 6/18 (33.3%)
    Tricuspid valve incompetence 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Ventricular extrasystoles 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Ear and labyrinth disorders
    Auricular swelling 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Cerumen impaction 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Ear discomfort 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Ear disorder 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Ear pain 5/39 (12.8%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    External ear inflammation 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hypoacusis 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Mastoid disorder 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Tinnitus 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Vertigo 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Endocrine disorders
    Hypothyroidism 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Eye disorders
    Conjunctival haemorrhage 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Conjunctival hyperaemia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Conjunctivitis 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Diplopia 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Dry eye 2/39 (5.1%) 2/18 (11.1%) 2/17 (11.8%) 2/16 (12.5%) 3/18 (16.7%)
    Erythema of eyelid 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Eye haemorrhage 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Eye irritation 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Eye pain 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Eye swelling 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Eyelid oedema 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Lacrimation increased 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Meibomianitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Ocular hyperaemia 0/39 (0%) 1/18 (5.6%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Ocular icterus 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Orbital oedema 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Papilloedema 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Photophobia 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Photopsia 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pupil fixed 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Retinal haemorrhage 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Scleral haemorrhage 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Vision blurred 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Visual acuity reduced 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Visual disturbance 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Vitreous detachment 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Vitreous floaters 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 3/39 (7.7%) 1/18 (5.6%) 3/17 (17.6%) 1/16 (6.3%) 0/18 (0%)
    Abdominal distension 11/39 (28.2%) 2/18 (11.1%) 4/17 (23.5%) 2/16 (12.5%) 1/18 (5.6%)
    Abdominal hernia 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Abdominal pain 15/39 (38.5%) 4/18 (22.2%) 4/17 (23.5%) 1/16 (6.3%) 8/18 (44.4%)
    Abdominal pain lower 2/39 (5.1%) 1/18 (5.6%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Abdominal pain upper 1/39 (2.6%) 1/18 (5.6%) 2/17 (11.8%) 0/16 (0%) 0/18 (0%)
    Abdominal tenderness 3/39 (7.7%) 1/18 (5.6%) 0/17 (0%) 2/16 (12.5%) 0/18 (0%)
    Anal discomfort 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Anal fissure 0/39 (0%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Ascites 3/39 (7.7%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 2/18 (11.1%)
    Breath odour 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Caecitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Chapped lips 0/39 (0%) 0/18 (0%) 2/17 (11.8%) 0/16 (0%) 0/18 (0%)
    Cheilitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Colitis 1/39 (2.6%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Colonic polyp 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Constipation 15/39 (38.5%) 8/18 (44.4%) 8/17 (47.1%) 6/16 (37.5%) 7/18 (38.9%)
    Diarrhoea 28/39 (71.8%) 13/18 (72.2%) 15/17 (88.2%) 12/16 (75%) 12/18 (66.7%)
    Diarrhoea haemorrhagic 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Diverticulum 3/39 (7.7%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Diverticulum intestinal 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Dry mouth 4/39 (10.3%) 0/18 (0%) 4/17 (23.5%) 0/16 (0%) 6/18 (33.3%)
    Dyspepsia 3/39 (7.7%) 4/18 (22.2%) 6/17 (35.3%) 4/16 (25%) 2/18 (11.1%)
    Dysphagia 2/39 (5.1%) 3/18 (16.7%) 2/17 (11.8%) 1/16 (6.3%) 2/18 (11.1%)
    Enteritis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Epigastric discomfort 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Faecal incontinence 2/39 (5.1%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Faeces discoloured 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Faeces hard 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Flatulence 3/39 (7.7%) 2/18 (11.1%) 2/17 (11.8%) 0/16 (0%) 1/18 (5.6%)
    Frequent bowel movements 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Gastrointestinal haemorrhage 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Gastrointestinal necrosis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Gastrooesophageal reflux disease 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Gingival bleeding 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Gingival pain 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Gingivitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Glossodynia 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Haematemesis 1/39 (2.6%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Haematochezia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Haemorrhoidal haemorrhage 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Haemorrhoids 3/39 (7.7%) 5/18 (27.8%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Hiatus hernia 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Ileus 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Lip blister 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Lip disorder 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Lip dry 3/39 (7.7%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 1/18 (5.6%)
    Lip oedema 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Lip pain 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Lip ulceration 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Melaena 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Mouth haemorrhage 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Mouth ulceration 3/39 (7.7%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Mucous stools 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Nausea 29/39 (74.4%) 6/18 (33.3%) 14/17 (82.4%) 10/16 (62.5%) 12/18 (66.7%)
    Neutropenic colitis 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Odynophagia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Oesophagitis 2/39 (5.1%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Oral mucosal blistering 3/39 (7.7%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Oral mucosal petechiae 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Oral pain 0/39 (0%) 0/18 (0%) 0/17 (0%) 2/16 (12.5%) 0/18 (0%)
    Oral soft tissue disorder 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Peritonitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Poor dental condition 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Proctalgia 4/39 (10.3%) 4/18 (22.2%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Rectal haemorrhage 0/39 (0%) 2/18 (11.1%) 2/17 (11.8%) 0/16 (0%) 1/18 (5.6%)
    Reflux gastritis 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Retching 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Stomach discomfort 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Stomatitis 21/39 (53.8%) 13/18 (72.2%) 11/17 (64.7%) 15/16 (93.8%) 10/18 (55.6%)
    Tongue coated 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Tongue haemorrhage 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Tongue ulceration 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Tooth disorder 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Toothache 0/39 (0%) 2/18 (11.1%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Vomiting 21/39 (53.8%) 7/18 (38.9%) 11/17 (64.7%) 4/16 (25%) 9/18 (50%)
    General disorders
    Adverse drug reaction 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Application site pruritus 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Application site vesicles 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Asthenia 11/39 (28.2%) 3/18 (16.7%) 8/17 (47.1%) 1/16 (6.3%) 8/18 (44.4%)
    Axillary pain 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Catheter related complication 1/39 (2.6%) 4/18 (22.2%) 2/17 (11.8%) 5/16 (31.3%) 2/18 (11.1%)
    Catheter site erythema 4/39 (10.3%) 2/18 (11.1%) 2/17 (11.8%) 2/16 (12.5%) 0/18 (0%)
    Catheter site excoriation 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Catheter site haemorrhage 3/39 (7.7%) 2/18 (11.1%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Catheter site oedema 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Catheter site pain 4/39 (10.3%) 2/18 (11.1%) 2/17 (11.8%) 0/16 (0%) 1/18 (5.6%)
    Catheter site pruritus 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Catheter site rash 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Catheter site related reaction 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Chest discomfort 3/39 (7.7%) 1/18 (5.6%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Chest pain 4/39 (10.3%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 2/18 (11.1%)
    Chills 18/39 (46.2%) 8/18 (44.4%) 8/17 (47.1%) 6/16 (37.5%) 7/18 (38.9%)
    Face oedema 4/39 (10.3%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 2/18 (11.1%)
    Facial pain 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Fatigue 16/39 (41%) 7/18 (38.9%) 7/17 (41.2%) 3/16 (18.8%) 9/18 (50%)
    Feeling cold 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Gait disturbance 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Generalised oedema 2/39 (5.1%) 0/18 (0%) 1/17 (5.9%) 2/16 (12.5%) 1/18 (5.6%)
    Hypothermia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Infusion site pain 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Infusion site reaction 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Infusion site vesicles 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Infusion site warmth 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Injection site pain 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Localised oedema 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Malaise 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Mucosal inflammation 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Nodule 3/39 (7.7%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Non-cardiac chest pain 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Oedema 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 2/18 (11.1%)
    Oedema peripheral 17/39 (43.6%) 3/18 (16.7%) 7/17 (41.2%) 3/16 (18.8%) 9/18 (50%)
    Pain 5/39 (12.8%) 3/18 (16.7%) 4/17 (23.5%) 4/16 (25%) 3/18 (16.7%)
    Performance status decreased 0/39 (0%) 0/18 (0%) 2/17 (11.8%) 1/16 (6.3%) 0/18 (0%)
    Pyrexia 13/39 (33.3%) 6/18 (33.3%) 2/17 (11.8%) 1/16 (6.3%) 3/18 (16.7%)
    Sensation of foreign body 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Suprapubic pain 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Tenderness 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Thirst 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Upper extremity mass 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Hepatobiliary disorders
    Cholelithiasis 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Cholestasis 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Dilatation intrahepatic duct acquired 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hepatic cyst 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Hepatic steatosis 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Hepatosplenomegaly 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hyperbilirubinaemia 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 2/18 (11.1%)
    Jaundice 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Immune system disorders
    Drug hypersensitivity 5/39 (12.8%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Infections and infestations
    Acute sinusitis 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Anorectal cellulitis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Anorectal infection bacterial 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Bacteraemia 1/39 (2.6%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Bacterial disease carrier 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Bacterial infection 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Bronchiolitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Bronchopulmonary aspergillosis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Candidiasis 3/39 (7.7%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Catheter site cellulitis 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Cellulitis 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 3/16 (18.8%) 1/18 (5.6%)
    Clostridial infection 3/39 (7.7%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Clostridium difficile colitis 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 2/18 (11.1%)
    Diverticulitis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Enterobacter bacteraemia 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Enterococcal bacteraemia 2/39 (5.1%) 0/18 (0%) 4/17 (23.5%) 2/16 (12.5%) 1/18 (5.6%)
    Enterococcal infection 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 2/16 (12.5%) 0/18 (0%)
    Enterococcal sepsis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Escherichia bacteraemia 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Folliculitis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Fungaemia 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Fungal skin infection 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Furuncle 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Herpes simplex 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Liver abscess 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Lung infection 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Nasopharyngitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Oral candidiasis 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 2/18 (11.1%)
    Oral herpes 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Parotitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Perianal abscess 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pharyngitis 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Pneumonia 3/39 (7.7%) 1/18 (5.6%) 0/17 (0%) 2/16 (12.5%) 2/18 (11.1%)
    Pneumonia bacterial 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Pneumonia fungal 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pseudomonal bacteraemia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Rectal abscess 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Respiratory tract infection 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Rhinitis 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Sepsis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Septic shock 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Sialoadenitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Sinusitis 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Staphylococcal abscess 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Staphylococcal bacteraemia 2/39 (5.1%) 3/18 (16.7%) 3/17 (17.6%) 3/16 (18.8%) 1/18 (5.6%)
    Staphylococcal infection 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Stenotrophomonas infection 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Streptococcal bacteraemia 0/39 (0%) 0/18 (0%) 0/17 (0%) 3/16 (18.8%) 0/18 (0%)
    Subcutaneous abscess 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Torulopsis infection 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Upper respiratory tract infection 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Urinary tract infection 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Urinary tract infection bacterial 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Urinary tract infection enterococcal 1/39 (2.6%) 0/18 (0%) 2/17 (11.8%) 0/16 (0%) 1/18 (5.6%)
    Viral pharyngitis 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Viral upper respiratory tract infection 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Vulval cellulitis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Injury, poisoning and procedural complications
    Allergic transfusion reaction 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Chemical eye injury 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Contusion 3/39 (7.7%) 0/18 (0%) 0/17 (0%) 3/16 (18.8%) 2/18 (11.1%)
    Excoriation 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Fall 3/39 (7.7%) 2/18 (11.1%) 1/17 (5.9%) 2/16 (12.5%) 1/18 (5.6%)
    Head injury 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Joint injury 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Limb injury 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Post procedural complication 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Post procedural haematoma 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Post procedural haemorrhage 0/39 (0%) 2/18 (11.1%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Procedural dizziness 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Procedural pain 6/39 (15.4%) 2/18 (11.1%) 2/17 (11.8%) 5/16 (31.3%) 2/18 (11.1%)
    Procedural site reaction 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Rib fracture 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Scratch 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Skin laceration 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Subdural haematoma 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Thermal burn 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Tooth fracture 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Transfusion reaction 2/39 (5.1%) 1/18 (5.6%) 4/17 (23.5%) 1/16 (6.3%) 2/18 (11.1%)
    Vertebral injury 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Alanine aminotransferase increased 2/39 (5.1%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Aspartate aminotransferase increased 2/39 (5.1%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Bacteria sputum identified 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Bacteria stool identified 2/39 (5.1%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Bacteria urine identified 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Blood alkaline phosphatase increased 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 2/16 (12.5%) 0/18 (0%)
    Blood bilirubin increased 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Blood creatinine increased 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 2/16 (12.5%) 0/18 (0%)
    Blood lactate dehydrogenase increased 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Blood phosphorus decreased 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Blood urea increased 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Blood urine present 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Breath sounds abnormal 9/39 (23.1%) 4/18 (22.2%) 2/17 (11.8%) 0/16 (0%) 2/18 (11.1%)
    Bronchoscopy abnormal 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Cardiac murmur 2/39 (5.1%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 2/18 (11.1%)
    Computerised tomogram abdomen abnormal 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Computerised tomogram abnormal 2/39 (5.1%) 1/18 (5.6%) 2/17 (11.8%) 1/16 (6.3%) 0/18 (0%)
    Culture stool positive 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Ejection fraction decreased 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Electrocardiogram QT corrected interval prolonged 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Electrocardiogram ST-T segment abnormal 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Electrocardiogram T wave abnormal 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Electrocardiogram T wave inversion 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Electrocardiogram abnormal 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Electrocardiogram repolarisation abnormality 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Heart rate irregular 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Heart sounds abnormal 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    International normalised ratio increased 1/39 (2.6%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Liver function test abnormal 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Methicillin-resistant staphylococcal aureus test positive 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Nuclear magnetic resonance imaging abnormal 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Nuclear magnetic resonance imaging brain abnormal 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Occult blood 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Oxygen saturation decreased 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Prothrombin time prolonged 0/39 (0%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Ultrasound kidney 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Urine output decreased 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 2/16 (12.5%) 1/18 (5.6%)
    Varicella zoster virus serology positive 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Weight decreased 4/39 (10.3%) 2/18 (11.1%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Weight increased 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Metabolism and nutrition disorders
    Anorexia 12/39 (30.8%) 11/18 (61.1%) 13/17 (76.5%) 5/16 (31.3%) 10/18 (55.6%)
    Cachexia 2/39 (5.1%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Decreased appetite 9/39 (23.1%) 2/18 (11.1%) 2/17 (11.8%) 1/16 (6.3%) 3/18 (16.7%)
    Dehydration 3/39 (7.7%) 1/18 (5.6%) 4/17 (23.5%) 0/16 (0%) 2/18 (11.1%)
    Fluid overload 4/39 (10.3%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Fluid retention 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 2/18 (11.1%)
    Gout 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 2/18 (11.1%)
    Hypercalcaemia 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Hypercreatininaemia 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Hyperglycaemia 8/39 (20.5%) 3/18 (16.7%) 4/17 (23.5%) 2/16 (12.5%) 0/18 (0%)
    Hyperkalaemia 3/39 (7.7%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Hypermagnesaemia 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Hypernatraemia 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hyperphosphataemia 2/39 (5.1%) 2/18 (11.1%) 0/17 (0%) 0/16 (0%) 2/18 (11.1%)
    Hyperuricaemia 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Hypoalbuminaemia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Hypocalcaemia 4/39 (10.3%) 2/18 (11.1%) 2/17 (11.8%) 0/16 (0%) 1/18 (5.6%)
    Hypoglycaemia 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hypokalaemia 30/39 (76.9%) 10/18 (55.6%) 15/17 (88.2%) 9/16 (56.3%) 15/18 (83.3%)
    Hypomagnesaemia 18/39 (46.2%) 10/18 (55.6%) 13/17 (76.5%) 7/16 (43.8%) 10/18 (55.6%)
    Hyponatraemia 2/39 (5.1%) 0/18 (0%) 3/17 (17.6%) 2/16 (12.5%) 0/18 (0%)
    Hypophosphataemia 11/39 (28.2%) 0/18 (0%) 9/17 (52.9%) 5/16 (31.3%) 4/18 (22.2%)
    Hypovolaemia 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Malnutrition 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 3/18 (16.7%)
    Metabolic acidosis 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 7/39 (17.9%) 0/18 (0%) 2/17 (11.8%) 2/16 (12.5%) 2/18 (11.1%)
    Back pain 16/39 (41%) 4/18 (22.2%) 4/17 (23.5%) 2/16 (12.5%) 6/18 (33.3%)
    Bone pain 1/39 (2.6%) 2/18 (11.1%) 1/17 (5.9%) 2/16 (12.5%) 0/18 (0%)
    Flank pain 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Groin pain 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Joint effusion 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Joint range of motion decreased 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Limb discomfort 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Muscle spasms 4/39 (10.3%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Muscle tightness 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Muscular weakness 2/39 (5.1%) 1/18 (5.6%) 3/17 (17.6%) 0/16 (0%) 0/18 (0%)
    Musculoskeletal chest pain 2/39 (5.1%) 2/18 (11.1%) 2/17 (11.8%) 0/16 (0%) 2/18 (11.1%)
    Musculoskeletal discomfort 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Musculoskeletal pain 2/39 (5.1%) 2/18 (11.1%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Musculoskeletal stiffness 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Myalgia 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 1/18 (5.6%)
    Neck pain 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Nodule on extremity 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Osteoarthritis 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Pain in extremity 10/39 (25.6%) 3/18 (16.7%) 2/17 (11.8%) 0/16 (0%) 1/18 (5.6%)
    Pain in jaw 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Sensation of heaviness 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Synovial cyst 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Synovitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Benign neoplasm of adrenal gland 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Central nervous system leukaemia 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Lipoma 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Lung neoplasm 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Tumour lysis syndrome 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Nervous system disorders
    Ageusia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Brain oedema 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Burning sensation 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Cerebral haemorrhage 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Cerebral ischaemia 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Cognitive disorder 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Coordination abnormal 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Dizziness 7/39 (17.9%) 3/18 (16.7%) 4/17 (23.5%) 7/16 (43.8%) 2/18 (11.1%)
    Dysaesthesia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Dysarthria 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Dysgeusia 5/39 (12.8%) 1/18 (5.6%) 3/17 (17.6%) 1/16 (6.3%) 5/18 (27.8%)
    Encephalopathy 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Extrapyramidal disorder 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Facial palsy 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Grand mal convulsion 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Headache 14/39 (35.9%) 7/18 (38.9%) 3/17 (17.6%) 7/16 (43.8%) 5/18 (27.8%)
    Hepatic encephalopathy 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Hypoaesthesia 3/39 (7.7%) 4/18 (22.2%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Hyposmia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Intracranial pressure increased 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Lethargy 2/39 (5.1%) 0/18 (0%) 2/17 (11.8%) 0/16 (0%) 0/18 (0%)
    Memory impairment 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Neuropathy peripheral 2/39 (5.1%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Paraesthesia 3/39 (7.7%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Parosmia 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Peripheral sensory neuropathy 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Presyncope 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 2/18 (11.1%)
    Psychomotor hyperactivity 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Restless legs syndrome 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Sciatica 0/39 (0%) 0/18 (0%) 2/17 (11.8%) 0/16 (0%) 0/18 (0%)
    Somnolence 3/39 (7.7%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 2/18 (11.1%)
    Subarachnoid haemorrhage 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Syncope 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 2/16 (12.5%) 0/18 (0%)
    Syncope vasovagal 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Transient ischaemic attack 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Tremor 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Psychiatric disorders
    Agitation 7/39 (17.9%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Anxiety 11/39 (28.2%) 6/18 (33.3%) 6/17 (35.3%) 5/16 (31.3%) 3/18 (16.7%)
    Bradyphrenia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Confusional state 6/39 (15.4%) 1/18 (5.6%) 2/17 (11.8%) 0/16 (0%) 4/18 (22.2%)
    Delirium 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Delusional disorder, unspecified type 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Depressed mood 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Depression 6/39 (15.4%) 1/18 (5.6%) 5/17 (29.4%) 1/16 (6.3%) 3/18 (16.7%)
    Disorientation 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Hallucination 2/39 (5.1%) 1/18 (5.6%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Hallucination, visual 3/39 (7.7%) 1/18 (5.6%) 1/17 (5.9%) 2/16 (12.5%) 1/18 (5.6%)
    Hallucinations, mixed 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Insomnia 14/39 (35.9%) 3/18 (16.7%) 9/17 (52.9%) 6/16 (37.5%) 5/18 (27.8%)
    Mental status changes 2/39 (5.1%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Nervousness 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Nightmare 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Restlessness 3/39 (7.7%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Renal and urinary disorders
    Azotaemia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Chromaturia 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Dysuria 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Haematuria 4/39 (10.3%) 3/18 (16.7%) 1/17 (5.9%) 1/16 (6.3%) 3/18 (16.7%)
    Nephrolithiasis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Nocturia 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pollakiuria 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 4/18 (22.2%)
    Renal cyst 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Renal failure 0/39 (0%) 0/18 (0%) 0/17 (0%) 2/16 (12.5%) 1/18 (5.6%)
    Renal failure acute 4/39 (10.3%) 0/18 (0%) 2/17 (11.8%) 2/16 (12.5%) 0/18 (0%)
    Urethral pain 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Urinary hesitation 3/39 (7.7%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Urinary incontinence 3/39 (7.7%) 1/18 (5.6%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Urinary retention 3/39 (7.7%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Urine odour abnormal 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Reproductive system and breast disorders
    Epididymitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Postmenopausal haemorrhage 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Scrotal irritation 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Testicular swelling 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Vaginal laceration 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Vulvovaginal discomfort 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Atelectasis 1/39 (2.6%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Cough 8/39 (20.5%) 6/18 (33.3%) 3/17 (17.6%) 4/16 (25%) 6/18 (33.3%)
    Dysphonia 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Dyspnoea 12/39 (30.8%) 4/18 (22.2%) 2/17 (11.8%) 2/16 (12.5%) 6/18 (33.3%)
    Dyspnoea exertional 4/39 (10.3%) 1/18 (5.6%) 0/17 (0%) 2/16 (12.5%) 2/18 (11.1%)
    Epistaxis 9/39 (23.1%) 5/18 (27.8%) 4/17 (23.5%) 1/16 (6.3%) 4/18 (22.2%)
    Haemoptysis 2/39 (5.1%) 1/18 (5.6%) 2/17 (11.8%) 0/16 (0%) 1/18 (5.6%)
    Hiccups 3/39 (7.7%) 2/18 (11.1%) 7/17 (41.2%) 4/16 (25%) 0/18 (0%)
    Hypoventilation 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hypoxia 2/39 (5.1%) 3/18 (16.7%) 2/17 (11.8%) 0/16 (0%) 1/18 (5.6%)
    Increased upper airway secretion 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Interstitial lung disease 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Lung infiltration 2/39 (5.1%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Nasal congestion 5/39 (12.8%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Nasal dryness 1/39 (2.6%) 1/18 (5.6%) 1/17 (5.9%) 1/16 (6.3%) 2/18 (11.1%)
    Nasal mucosal disorder 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pharyngeal haemorrhage 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pharyngolaryngeal pain 4/39 (10.3%) 5/18 (27.8%) 2/17 (11.8%) 1/16 (6.3%) 3/18 (16.7%)
    Pleural effusion 2/39 (5.1%) 3/18 (16.7%) 2/17 (11.8%) 0/16 (0%) 4/18 (22.2%)
    Pleuritic pain 1/39 (2.6%) 1/18 (5.6%) 1/17 (5.9%) 1/16 (6.3%) 1/18 (5.6%)
    Pneumothorax 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Postnasal drip 3/39 (7.7%) 1/18 (5.6%) 0/17 (0%) 2/16 (12.5%) 0/18 (0%)
    Productive cough 1/39 (2.6%) 1/18 (5.6%) 2/17 (11.8%) 2/16 (12.5%) 4/18 (22.2%)
    Pulmonary alveolar haemorrhage 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pulmonary congestion 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pulmonary hypertension 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pulmonary mass 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Pulmonary oedema 1/39 (2.6%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Rales 7/39 (17.9%) 3/18 (16.7%) 0/17 (0%) 1/16 (6.3%) 3/18 (16.7%)
    Respiratory distress 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Respiratory failure 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Rhinitis allergic 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Rhinorrhoea 4/39 (10.3%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Rhonchi 2/39 (5.1%) 1/18 (5.6%) 1/17 (5.9%) 2/16 (12.5%) 0/18 (0%)
    Sinus congestion 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Sinus disorder 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Tachypnoea 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Throat irritation 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Wheezing 0/39 (0%) 2/18 (11.1%) 0/17 (0%) 1/16 (6.3%) 2/18 (11.1%)
    Skin and subcutaneous tissue disorders
    Alopecia 8/39 (20.5%) 3/18 (16.7%) 5/17 (29.4%) 6/16 (37.5%) 3/18 (16.7%)
    Blister 2/39 (5.1%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Blood blister 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Decubitus ulcer 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Dermatitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Dermatitis contact 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Drug eruption 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Dry skin 4/39 (10.3%) 0/18 (0%) 2/17 (11.8%) 0/16 (0%) 0/18 (0%)
    Ecchymosis 3/39 (7.7%) 0/18 (0%) 1/17 (5.9%) 2/16 (12.5%) 1/18 (5.6%)
    Erythema 4/39 (10.3%) 1/18 (5.6%) 3/17 (17.6%) 2/16 (12.5%) 4/18 (22.2%)
    Exfoliative rash 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Facial wasting 0/39 (0%) 2/18 (11.1%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hidradenitis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Hyperhidrosis 6/39 (15.4%) 4/18 (22.2%) 2/17 (11.8%) 0/16 (0%) 2/18 (11.1%)
    Hypoaesthesia facial 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Increased tendency to bruise 1/39 (2.6%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Ingrowing nail 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Night sweats 6/39 (15.4%) 2/18 (11.1%) 1/17 (5.9%) 0/16 (0%) 1/18 (5.6%)
    Onychoclasis 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Pain of skin 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Palmar erythema 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Palmar-plantar erythrodysaesthesia syndrome 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Periorbital oedema 2/39 (5.1%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Petechiae 2/39 (5.1%) 4/18 (22.2%) 2/17 (11.8%) 4/16 (25%) 2/18 (11.1%)
    Pruritus 9/39 (23.1%) 2/18 (11.1%) 1/17 (5.9%) 3/16 (18.8%) 3/18 (16.7%)
    Pruritus generalised 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Rash 12/39 (30.8%) 3/18 (16.7%) 7/17 (41.2%) 3/16 (18.8%) 1/18 (5.6%)
    Rash erythematous 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Rash generalised 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Rash macular 1/39 (2.6%) 0/18 (0%) 3/17 (17.6%) 1/16 (6.3%) 0/18 (0%)
    Rash maculo-papular 2/39 (5.1%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Rash pruritic 3/39 (7.7%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Red man syndrome 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Seborrhoeic dermatitis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Skin disorder 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Skin exfoliation 2/39 (5.1%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Skin lesion 0/39 (0%) 1/18 (5.6%) 1/17 (5.9%) 1/16 (6.3%) 0/18 (0%)
    Stasis dermatitis 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Swelling face 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Transient acantholytic dermatosis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Urticaria 3/39 (7.7%) 2/18 (11.1%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Surgical and medical procedures
    Post procedural drainage 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Vascular disorders
    Aortic arteriosclerosis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Deep vein thrombosis 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Flushing 6/39 (15.4%) 0/18 (0%) 1/17 (5.9%) 2/16 (12.5%) 1/18 (5.6%)
    Haematoma 2/39 (5.1%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 1/18 (5.6%)
    Hot flush 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Hypertension 8/39 (20.5%) 3/18 (16.7%) 1/17 (5.9%) 3/16 (18.8%) 3/18 (16.7%)
    Hypotension 17/39 (43.6%) 8/18 (44.4%) 7/17 (41.2%) 7/16 (43.8%) 7/18 (38.9%)
    Jugular vein distension 0/39 (0%) 0/18 (0%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Orthostatic hypotension 5/39 (12.8%) 1/18 (5.6%) 1/17 (5.9%) 0/16 (0%) 0/18 (0%)
    Thrombophlebitis 0/39 (0%) 1/18 (5.6%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Vascular calcification 1/39 (2.6%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 0/18 (0%)
    Vasculitis 0/39 (0%) 0/18 (0%) 0/17 (0%) 1/16 (6.3%) 0/18 (0%)
    Vasodilatation 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)
    Vena cava thrombosis 0/39 (0%) 0/18 (0%) 0/17 (0%) 0/16 (0%) 1/18 (5.6%)

    Limitations/Caveats

    Further study is needed to confirm the results due to limited sampling size. Statistical fields are not included here because no statistical testings were performed to compare any of the treatment groups. No p-values or odds ratios were reported.

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title Mike Johnston, Senior Director Regulatory Affairs
    Organization Sunesis Pharmaceuticals, Inc.
    Phone (650) 266-3727
    Email mjohnston@sunesis.com
    Responsible Party:
    Sunesis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT00541866
    Other Study ID Numbers:
    • SPO-0012
    First Posted:
    Oct 10, 2007
    Last Update Posted:
    Jan 9, 2018
    Last Verified:
    Dec 1, 2017