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Dose Escalation, Combination Chemotherapy Safety Study of Birinapant (TL32711), in Subjects With Advanced or Metastatic Solid Tumors

Sponsor
TetraLogic Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01188499
Collaborator
(none)
176
Enrollment
7
Locations
5
Arms
41
Duration (Months)
25.1
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a dose escalation safety study of birinapant (TL32711) in combination with chemotherapy in subjects with advanced or metastatic solid tumors.

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

Detailed Description

The purpose of this study is to determine the safety and maximum tolerated dose of birinapant (TL32711) as a 30 minute intravenous infusion once a week, for 2 consecutive weeks, when combined with standard regimens of chemotherapy in subjects with advanced or metastatic solid tumors. Additionally the study will assess anti-tumor activity, pharmacokinetics, and exploratory biomarkers as a measurement of pharmacodynamic effects.

Study Design

Study Type:
Interventional
Actual Enrollment :
176 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1B/2A, Open-label, Non-randomized, Multi-arm Study of TL32711 in Combination With Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors
Study Start Date :
Oct 1, 2010
Actual Primary Completion Date :
Oct 1, 2013
Actual Study Completion Date :
Mar 1, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: Carboplatin/Paclitaxel + Birinapant

Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).

Drug: Birinapant
Other Names:
  • TL32711

    		•
    Experimental: Irinotecan + Birinapant

    Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).

    Drug: Birinapant
    Other Names:
  • TL32711

    		•
    Experimental: Docetaxel + Birinapant

    Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle).

    Drug: Birinapant
    Other Names:
  • TL32711

    		•
    Experimental: Gemcitabine + Birinapant

    Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle).

    Drug: Birinapant
    Other Names:
  • TL32711

    		•
    Experimental: Liposomal Doxorubicin + Birinapant

    Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + birinapant (TL32711) once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle).

    Drug: Birinapant
    Other Names:
  • TL32711

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Subjects With Adverse Events as a Measure of Safety and Tolerability [1 Cycle (3-4 weeks)]

      Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters

    Secondary Outcome Measures

    1. Evaluation of Anti-tumor Efficacy [Every 2 cycles]

      Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST) and time to progression

    2. Evaluation of Pharmacokinetics and Translational Biomarkers [Cycle 1 and Cycle 2]

      Measurement of TL32711 pharmacokinetics: Maximum plasma concentration (Cmax), area under the curve (AUC), half-life (t1/2) and assessment of translational biomarkers in plasma, PBMC's and tumor biopsies. Gene expression profiling of tumor tissue.

    Eligibility Criteria

    Criteria

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

    • Confirmed advanced or metastatic malignancy for which the proposed chemotherapy regimen is appropriate in the judgment of the Investigator.

    • Prior therapy in dose-escalation and expansion cohorts:

    • Dose-escalation cohorts: Subjects may be naïve or may have received prior therapy with the specific chemotherapeutic agent(s) being recommended in the combination arm, provided the subject did not experience life-threatening toxicity attributed to the specific agent(s).

    • Expansion cohorts: Subjects have advanced colorectal cancer that had been previously determined to be KRAS mutant. Subjects naïve to irinotecan may be enrolled, and the KRAS mutation status may be wild type or mutant. Subjects previously treated with an irinotecan containing regimen may be enrolled only if they have been previously determined to be KRAS wild type. The irinotecan regimen must not have been associated with life threatening adverse events.

    • Subjects evaluated for Arm 5 (liposomal doxorubicin) may not have received >300 mg/m2 cumulative dose of anthracycline.

    • Life expectancy >3 months.

    • Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

    • Adequate renal function

    • Adequate hepatic function

    • Adequate bone marrow function

    • Women of childbearing potential must have a negative serum pregnancy test.

    • Women of childbearing potential must agree to use 2 methods of adequate contraception (ie, hormonal and barrier method) prior to enrollment, during the study, and for a period of 30 days following the last dose of TL32711. Males who are sexually active must agree to use a condom during the study and for a period of 30 days following the last dose of TL32711, and if their partner is of childbearing potential, she must agree to use a secondary method of contraception (ie, hormonal, intrauterine device, barrier) during the study and for a period of 30 days following the last dose of TL32711.

    Exclusion Criteria:

    • Recent anti-cancer treatment defined as:

    • Standard or investigational anti-cancer therapy within 4 weeks prior to first dose of TL32711. Exception: continued hormonal interventions for prostate cancer.

    • Radiation therapy within 2 weeks prior to the first dose of TL32711.

    • Major surgery within 4 weeks prior to the first dose of TL32711. Subjects must be well recovered from acute effects of surgery prior to enrollment.

    • Known or suspected diagnosis of human immunodeficiency virus or chronic active Hepatitis B or C.

    • Symptomatic or uncontrolled brain metastases requiring current treatment.

    • Impaired cardiac function or clinically significant cardiac disease

    • QT interval corrected for heart rate (QTcB) >480 msec (including subjects on medication).

    • Lack of recovery of prior adverse events to Grade ≤1 severity (NCI CTCAE v4) (except alopecia) due to therapy administered prior to the initiation of study drug dosing.

    • Nursing or pregnant women.

    • Known allergy to any of the formulation components of TL32711.

    • Any concurrent disease and/or medical condition that in the opinion of the Investigator that would prevent the subject's participation, render the subject at excessive risk (including excessive risks due to the toxicity profile of the planned combination chemotherapeutic regimen), or limit the subject's compliance with the protocol's required evaluations.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Holy Cross Hospital Fort Lauderdale Florida United States 33308
    2 Barbara Ann Karmanos Cancer Center Detroit Michigan United States 48201
    3 Roswell Park Cancer Institute Buffalo New York United States 14263
    4 University of Pennsylvania Abramson Cancer Center Philadelphia Pennsylvania United States 19104
    5 Fox Chase Cancer Center Philadelphia Pennsylvania United States 19111
    6 Mary Crowley Cancer Research Center Dallas Texas United States 75201
    7 South Texas Accelerated Research Therapeutics (START) San Antonio Texas United States 78229

    Sponsors and Collaborators

    • TetraLogic Pharmaceuticals

    Investigators

    • Principal Investigator: John N Nemunaitis, MD, Mary Crowley Cancer Research Center
    • Principal Investigator: Ravi Amaravadi, MD, University of Pennsylvania, Abramson Cancer Center
    • Principal Investigator: Lainie P Martin, MD, Fox Chase Cancer Center
    • Principal Investigator: Alex Adjei, MD, PhD, Roswell Park Cancer Institute
    • Principal Investigator: Patricia LoRusso, DO, Barbara Ann Karmanos Cancer Center
    • Principal Investigator: Kyriakos P Papadopoulos, MD, South Texas Accelerated Research Therapeutics (START)
    • Principal Investigator: Zdenka Segota, MD, Holy Cross Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    TetraLogic Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01188499
    Other Study ID Numbers:
    • TL32711-POC-0078-PTL
    First Posted:
    Aug 25, 2010
    Last Update Posted:
    May 30, 2016
    Last Verified:
    Apr 1, 2016

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Arm 1: Carboplatin/Paclitaxel + Birinapant Arm 2: Irinotecan + Birinapant Arm 3: Docetaxel + Birinapant Arm 4: Gemcitabine + Birinapant Arm 5: Liposomal Doxorubicin + Birinapant
    Arm/Group Description Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy. Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
    Period Title: Overall Study
    STARTED 24 83 33 18 18
    COMPLETED 24 83 33 18 18
    NOT COMPLETED 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Arm 1: Carboplatin/Paclitaxel + Birinapant Arm 2: Irinotecan + Birinapant Arm 3: Docetaxel + Birinapant Arm 4: Gemcitabine + Birinapant Arm 5: Liposomal Doxorubicin + Birinapant Total
    Arm/Group Description Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy. Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy. Total of all reporting groups
    Overall Participants 24 83 33 18 18 176
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63
    (8.77)
    59.6
    (11.58)
    60.7
    (11.16)
    56.7
    (8.55)
    56.5
    (10.44)
    59.7
    (10.82)
    Sex: Female, Male (Count of Participants)
    Female
    13
    54.2%
    39
    47%
    15
    45.5%
    11
    61.1%
    13
    72.2%
    91
    51.7%
    Male
    11
    45.8%
    44
    53%
    18
    54.5%
    7
    38.9%
    5
    27.8%
    85
    48.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    1
    4.2%
    2
    2.4%
    1
    3%
    2
    11.1%
    2
    11.1%
    8
    4.5%
    Not Hispanic or Latino
    23
    95.8%
    81
    97.6%
    32
    97%
    16
    88.9%
    16
    88.9%
    168
    95.5%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5.6%
    1
    0.6%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    2
    8.3%
    12
    14.5%
    3
    9.1%
    3
    16.7%
    3
    16.7%
    23
    13.1%
    White
    22
    91.7%
    71
    85.5%
    30
    90.9%
    15
    83.3%
    13
    72.2%
    151
    85.8%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    5.6%
    1
    0.6%
    Region of Enrollment (participants) [Number]
    United States
    24
    100%
    83
    100%
    33
    100%
    18
    100%
    18
    100%
    176
    100%

    Outcome Measures

    1. Primary Outcome
    Title Number of Subjects With Adverse Events as a Measure of Safety and Tolerability
    Description Number of subjects with adverse events as a measure of safety and tolerability including changes in vital signs, electrocardiograms (ECGs), safety and laboratory parameters
    Time Frame 1 Cycle (3-4 weeks)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Arm 1: Carboplatin/Paclitaxel + TL32711 Arm 2: Irinotecan + TL32711 Arm 3: Docetaxel + TL32711 Arm 4: Gemcitabine + TL32711 Arm 5: Liposomal Doxorubicin
    Arm/Group Description Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy. Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
    Measure Participants 24 83 33 18 18
    Number [participants]
    24
    100%
    83
    100%
    33
    100%
    18
    100%
    18
    100%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 1: Carboplatin/Paclitaxel + TL32711, Arm 2: Irinotecan + TL32711, Arm 3: Docetaxel + TL32711, Arm 4: Gemcitabine + TL32711, Arm 5: Liposomal Doxorubicin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent
    Estimated Value 100
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Primary objective of safety and tolerability measured by percent participants experiencing at least one adverse event. No formal statistics performed.
    2. Secondary Outcome
    Title Evaluation of Anti-tumor Efficacy
    Description Tumor burden according to Response Evaluation Criteria in Solid Tumors (RECIST) and time to progression
    Time Frame Every 2 cycles

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT)
    Arm/Group Title Arm 1: Carboplatin/Paclitaxel + TL32711 Arm 2: Irinotecan + TL32711 Arm 3: Docetaxel + TL32711 Arm 4: Gemcitabine + TL32711 Arm 5: Liposomal Doxorubicin
    Arm/Group Description Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy. Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
    Measure Participants 24 83 33 18 18
    Number [participants]
    5
    20.8%
    8
    9.6%
    3
    9.1%
    2
    11.1%
    0
    0%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Arm 1: Carboplatin/Paclitaxel + TL32711, Arm 2: Irinotecan + TL32711, Arm 3: Docetaxel + TL32711, Arm 4: Gemcitabine + TL32711, Arm 5: Liposomal Doxorubicin
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Percent
    Estimated Value 10
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments Percent patients overall across all five arms demonstrating complete or partial response by RECIST. No formal statistics performed.
    3. Secondary Outcome
    Title Evaluation of Pharmacokinetics and Translational Biomarkers
    Description Measurement of TL32711 pharmacokinetics: Maximum plasma concentration (Cmax), area under the curve (AUC), half-life (t1/2) and assessment of translational biomarkers in plasma, PBMC's and tumor biopsies. Gene expression profiling of tumor tissue.
    Time Frame Cycle 1 and Cycle 2

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Arm 1: Carboplatin/Paclitaxel + Birinapant Arm 2: Irinotecan + Birinapant Arm 3: Docetaxel + Birinapant Arm 4: Gemcitabine + Birinapant Arm 5: Liposomal Doxorubicin + Birinapant
    Arm/Group Description Carboplatin (AUC 6/Paclitaxel (175 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Irinotecan (350 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Docetaxel (75 mg/m2/IV) once every 3 (q3) weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 1 week off for each cycle (3 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by one week off repeated every 3 weeks as tolerated in combination with chemotherapy Gemcitabine (1000 mg/m2/IV) once weekly (7 days +/- 2 days) for 3 consecutive weeks followed by 1 week off + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 week off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy. Liposomal doxorubicin (40 mg/m2/IV) every 4 weeks + TL32711 once weekly (7 days +/- 2 days) for 2 consecutive weeks followed by 2 weeks off for each cycle (4 weeks per cycle). TL32711: 30 minute intravenous (IV) infusion of TL32711 administered once weekly for two consecutive weeks followed by two weeks off repeated every 4 weeks as tolerated in combination with chemotherapy.
    All Cause Mortality
    Arm 1: Carboplatin/Paclitaxel + Birinapant Arm 2: Irinotecan + Birinapant Arm 3: Docetaxel + Birinapant Arm 4: Gemcitabine + Birinapant Arm 5: Liposomal Doxorubicin + Birinapant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Arm 1: Carboplatin/Paclitaxel + Birinapant Arm 2: Irinotecan + Birinapant Arm 3: Docetaxel + Birinapant Arm 4: Gemcitabine + Birinapant Arm 5: Liposomal Doxorubicin + Birinapant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/24 (37.5%) 41/83 (49.4%) 16/33 (48.5%) 13/18 (72.2%) 9/18 (50%)
    Blood and lymphatic system disorders
    Anaemia 2/24 (8.3%) 3/83 (3.6%) 2/33 (6.1%) 1/18 (5.6%) 1/18 (5.6%)
    Coagulopathy 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Disseminated intravascular coagulation 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Febrile neutropenia 0/24 (0%) 7/83 (8.4%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Neutropenia 0/24 (0%) 5/83 (6%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Leukocytosis 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Thrombocytopenia 0/24 (0%) 3/83 (3.6%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Pancytopenia 0/24 (0%) 3/83 (3.6%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Cardiac disorders
    Cardiac tamponade 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Stress cardiomyopathy 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Congenital, familial and genetic disorders
    Pyloric stenosis 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Gastrointestinal disorders
    Abdominal pain 0/24 (0%) 4/83 (4.8%) 1/33 (3%) 0/18 (0%) 2/18 (11.1%)
    Abdominal pain upper 1/24 (4.2%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Anal fissure 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Ascites 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Colitis 0/24 (0%) 3/83 (3.6%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Constipation 2/24 (8.3%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Diarrhoea 0/24 (0%) 6/83 (7.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Gastrointestinal haemorrhage 0/24 (0%) 2/83 (2.4%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Intestinal obstruction 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Intestinal perforation 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Lower gastrointestinal haemorrhage 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Nausea 1/24 (4.2%) 2/83 (2.4%) 0/33 (0%) 1/18 (5.6%) 1/18 (5.6%)
    Oesophagitis 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Reflux gastritis 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Small intestinal obstruction 1/24 (4.2%) 3/83 (3.6%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Upper gastrointestinal haemorrhage 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Vomiting 1/24 (4.2%) 5/83 (6%) 0/33 (0%) 2/18 (11.1%) 2/18 (11.1%)
    Caecitis 0/24 (0%) 2/83 (2.4%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Gastric ulcer 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Gastritis 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Haematemesis 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Oesophageal varices haemorrhage 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    General disorders
    Chest pain 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Death 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Disease progression 0/24 (0%) 4/83 (4.8%) 5/33 (15.2%) 1/18 (5.6%) 1/18 (5.6%)
    Generalized oedema 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Oedema peripheral 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Pain 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Pyrexia 0/24 (0%) 1/83 (1.2%) 2/33 (6.1%) 3/18 (16.7%) 1/18 (5.6%)
    Asthenia 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Fatigue 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Hepatobiliary disorders
    Bile duct stenosis 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Cholelithiasis 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Jaundice cholestatic 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Infections and infestations
    Bronchitis 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Cholangitis suppurative 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Cystitis 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Device related infection 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Empyema 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Escherichia bacteraemia 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Kidney infection 0/24 (0%) 0/83 (0%) 0/33 (0%) 2/18 (11.1%) 0/18 (0%)
    Pneumonia 3/24 (12.5%) 2/83 (2.4%) 5/33 (15.2%) 2/18 (11.1%) 1/18 (5.6%)
    Sepsis 1/24 (4.2%) 4/83 (4.8%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Septic shock 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Upper respiratory tract infection 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Urinary tract infection 0/24 (0%) 5/83 (6%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Bacterial sepsis 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Injury, poisoning and procedural complications
    Fall 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Femoral neck fracture 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Investigations
    Electrocardiogram QT prolonged 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    International normalised ratio increased 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Metabolism and nutrition disorders
    Dehydration 1/24 (4.2%) 8/83 (9.6%) 1/33 (3%) 1/18 (5.6%) 1/18 (5.6%)
    Failure to thrive 0/24 (0%) 0/83 (0%) 2/33 (6.1%) 0/18 (0%) 0/18 (0%)
    Fluid overload 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Hyperglycaemia 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Hyponatraemia 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Metabolic acidosis 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Hypokalaemia 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Hypovolaemia 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/24 (0%) 0/83 (0%) 0/33 (0%) 2/18 (11.1%) 0/18 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Intracranial tumour haemorrhage 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Colon cancer stage IV 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Nervous system disorders
    Spinal cord compression 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Psychiatric disorders
    Confusional state 1/24 (4.2%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Mental status changes 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Renal and urinary disorders
    Hydronephrosis 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Renal failure acute 0/24 (0%) 4/83 (4.8%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Urinary incontinence 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 0/24 (0%) 2/83 (2.4%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Bronchial fistula 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Dyspnoea 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Haemoptysis 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Pleural effusion 0/24 (0%) 0/83 (0%) 0/33 (0%) 3/18 (16.7%) 1/18 (5.6%)
    Pleurisy 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Pneumonitis 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Pulmonary embolism 0/24 (0%) 4/83 (4.8%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Pulmonary haemorrhage 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Pulmonary oedema 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Respiratory failure 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Aspiration 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Respiratory distress 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Vascular disorders
    Deep vein thrombosis 0/24 (0%) 1/83 (1.2%) 1/33 (3%) 1/18 (5.6%) 2/18 (11.1%)
    Venous thrombosis limb 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Hypotension 0/24 (0%) 5/83 (6%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Other (Not Including Serious) Adverse Events
    Arm 1: Carboplatin/Paclitaxel + Birinapant Arm 2: Irinotecan + Birinapant Arm 3: Docetaxel + Birinapant Arm 4: Gemcitabine + Birinapant Arm 5: Liposomal Doxorubicin + Birinapant
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 24/24 (100%) 83/83 (100%) 33/33 (100%) 18/18 (100%) 18/18 (100%)
    Blood and lymphatic system disorders
    Anaemia 16/24 (66.7%) 35/83 (42.2%) 13/33 (39.4%) 11/18 (61.1%) 4/18 (22.2%)
    Coagulopathy 0/24 (0%) 1/83 (1.2%) 1/33 (3%) 1/18 (5.6%) 1/18 (5.6%)
    Febrile neutropenia 0/24 (0%) 7/83 (8.4%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Iron deficiency anaemia 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 3/18 (16.7%) 1/18 (5.6%)
    Leukopenia 0/24 (0%) 8/83 (9.6%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Lymphadenopathy 2/24 (8.3%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Neutropenia 7/24 (29.2%) 23/83 (27.7%) 10/33 (30.3%) 7/18 (38.9%) 0/18 (0%)
    Thrombocytopenia 11/24 (45.8%) 28/83 (33.7%) 7/33 (21.2%) 8/18 (44.4%) 2/18 (11.1%)
    Cardiac disorders
    Atrial fibrillation 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Cardiac failure congestive 0/24 (0%) 1/83 (1.2%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Cardiac tamponade 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Cardiomyopathy 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Palpitations 1/24 (4.2%) 1/83 (1.2%) 0/33 (0%) 2/18 (11.1%) 1/18 (5.6%)
    Pericardial effusion 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Sinus tachycardia 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Stress cardiomyopathy 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Tachycardia 5/24 (20.8%) 6/83 (7.2%) 4/33 (12.1%) 3/18 (16.7%) 2/18 (11.1%)
    Ventricular extrasystoles 2/24 (8.3%) 2/83 (2.4%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Ear and labyrinth disorders
    External ear pain 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Hearing impaired 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Endocrine disorders
    Cushingoid 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Eye disorders
    Arcus lipoides 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Eye irritation 1/24 (4.2%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Lacrimation increased 3/24 (12.5%) 1/83 (1.2%) 4/33 (12.1%) 0/18 (0%) 0/18 (0%)
    Vision blurred 1/24 (4.2%) 2/83 (2.4%) 2/33 (6.1%) 0/18 (0%) 0/18 (0%)
    Gastrointestinal disorders
    Abdominal discomfort 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 2/18 (11.1%) 0/18 (0%)
    Abdominal distension 2/24 (8.3%) 3/83 (3.6%) 4/33 (12.1%) 6/18 (33.3%) 2/18 (11.1%)
    Abdominal pain 4/24 (16.7%) 32/83 (38.6%) 5/33 (15.2%) 5/18 (27.8%) 4/18 (22.2%)
    Abdominal pain lower 0/24 (0%) 2/83 (2.4%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Abdominal pain upper 4/24 (16.7%) 9/83 (10.8%) 5/33 (15.2%) 0/18 (0%) 1/18 (5.6%)
    Abdominal tenderness 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Ascites 2/24 (8.3%) 7/83 (8.4%) 4/33 (12.1%) 2/18 (11.1%) 3/18 (16.7%)
    Cheilitis 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Constipation 10/24 (41.7%) 25/83 (30.1%) 15/33 (45.5%) 5/18 (27.8%) 9/18 (50%)
    Diarrhoea 6/24 (25%) 58/83 (69.9%) 12/33 (36.4%) 5/18 (27.8%) 3/18 (16.7%)
    Dry mouth 1/24 (4.2%) 7/83 (8.4%) 4/33 (12.1%) 2/18 (11.1%) 1/18 (5.6%)
    Dyspepsia 2/24 (8.3%) 6/83 (7.2%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Dysphagia 0/24 (0%) 2/83 (2.4%) 3/33 (9.1%) 1/18 (5.6%) 1/18 (5.6%)
    Flatulence 0/24 (0%) 5/83 (6%) 1/33 (3%) 1/18 (5.6%) 1/18 (5.6%)
    Gastrooesophageal reflux disease 3/24 (12.5%) 2/83 (2.4%) 1/33 (3%) 2/18 (11.1%) 2/18 (11.1%)
    Gingival pain 1/24 (4.2%) 2/83 (2.4%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Haemorrhoidal haemorrhage 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Haemorrhoids 1/24 (4.2%) 1/83 (1.2%) 1/33 (3%) 0/18 (0%) 1/18 (5.6%)
    Mucous stools 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 1/18 (5.6%)
    Nausea 14/24 (58.3%) 62/83 (74.7%) 16/33 (48.5%) 9/18 (50%) 11/18 (61.1%)
    Oesophagitis 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Oral pain 1/24 (4.2%) 4/83 (4.8%) 3/33 (9.1%) 0/18 (0%) 0/18 (0%)
    Rectal haemorrhage 2/24 (8.3%) 1/83 (1.2%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Reflux gastritis 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Stomatitis 3/24 (12.5%) 11/83 (13.3%) 5/33 (15.2%) 4/18 (22.2%) 2/18 (11.1%)
    Tongue ulceration 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Vomiting 8/24 (33.3%) 47/83 (56.6%) 9/33 (27.3%) 10/18 (55.6%) 7/18 (38.9%)
    General disorders
    Asthenia 9/24 (37.5%) 23/83 (27.7%) 10/33 (30.3%) 7/18 (38.9%) 5/18 (27.8%)
    Catheter site reaction 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Chest discomfort 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Chest pain 1/24 (4.2%) 3/83 (3.6%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Chills 6/24 (25%) 14/83 (16.9%) 4/33 (12.1%) 2/18 (11.1%) 2/18 (11.1%)
    Device occlusion 1/24 (4.2%) 5/83 (6%) 2/33 (6.1%) 1/18 (5.6%) 0/18 (0%)
    Disease progression 0/24 (0%) 4/83 (4.8%) 5/33 (15.2%) 1/18 (5.6%) 1/18 (5.6%)
    Early satiety 0/24 (0%) 3/83 (3.6%) 2/33 (6.1%) 1/18 (5.6%) 1/18 (5.6%)
    Face oedema 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Fatigue 17/24 (70.8%) 57/83 (68.7%) 21/33 (63.6%) 13/18 (72.2%) 13/18 (72.2%)
    Generalized oedema 0/24 (0%) 2/83 (2.4%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Influenza like illness 1/24 (4.2%) 1/83 (1.2%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Infusion related reaction 3/24 (12.5%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Infusion site reaction 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Localised oedema 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Malaise 1/24 (4.2%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 1/18 (5.6%)
    Mucosal inflammation 0/24 (0%) 2/83 (2.4%) 10/33 (30.3%) 2/18 (11.1%) 1/18 (5.6%)
    Non-cardiac chest pain 0/24 (0%) 2/83 (2.4%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Oedema peripheral 9/24 (37.5%) 28/83 (33.7%) 15/33 (45.5%) 9/18 (50%) 9/18 (50%)
    Pain 2/24 (8.3%) 3/83 (3.6%) 2/33 (6.1%) 1/18 (5.6%) 0/18 (0%)
    Pyrexia 6/24 (25%) 16/83 (19.3%) 6/33 (18.2%) 8/18 (44.4%) 4/18 (22.2%)
    Hepatobiliary disorders
    Cholelithiasis 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Hyperbilirubinaemia 0/24 (0%) 1/83 (1.2%) 2/33 (6.1%) 0/18 (0%) 0/18 (0%)
    Jaundice 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Jaundice cholestatic 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Immune system disorders
    Drug hypersensitivity 3/24 (12.5%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Seasonal allergy 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Infections and infestations
    Bronchitis 2/24 (8.3%) 0/83 (0%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Candidiasis 0/24 (0%) 6/83 (7.2%) 5/33 (15.2%) 0/18 (0%) 2/18 (11.1%)
    Cellulitis 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Cystitis 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Device related infection 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Empyema 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Folliculitis 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Fungal infection 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Fungal skin infection 0/24 (0%) 2/83 (2.4%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Herpes zoster 2/24 (8.3%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Kidney infection 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Lower respiratory tract infection 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Oral candidiasis 0/24 (0%) 2/83 (2.4%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Pneumonia 4/24 (16.7%) 3/83 (3.6%) 3/33 (9.1%) 1/18 (5.6%) 2/18 (11.1%)
    Rhinitis 2/24 (8.3%) 6/83 (7.2%) 3/33 (9.1%) 1/18 (5.6%) 0/18 (0%)
    Sepsis 1/24 (4.2%) 4/83 (4.8%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Septic shock 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Sinusitis 2/24 (8.3%) 1/83 (1.2%) 2/33 (6.1%) 0/18 (0%) 1/18 (5.6%)
    Upper respiratory tract infection 3/24 (12.5%) 5/83 (6%) 3/33 (9.1%) 1/18 (5.6%) 2/18 (11.1%)
    Urinary tract infection 3/24 (12.5%) 12/83 (14.5%) 3/33 (9.1%) 1/18 (5.6%) 0/18 (0%)
    Urosepsis 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Vaginal infection 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Vulvovaginal candidiasis 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Vulvovaginal mycotic infection 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Injury, poisoning and procedural complications
    Contusion 2/24 (8.3%) 5/83 (6%) 1/33 (3%) 3/18 (16.7%) 0/18 (0%)
    Excoriation 2/24 (8.3%) 3/83 (3.6%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Fall 3/24 (12.5%) 2/83 (2.4%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Feeding tube complication 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Post procedural oedema 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Procedural pain 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Thermal burn 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Investigations
    Activated partial thromboplastin time prolonged 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Alanine aminotransferase increased 1/24 (4.2%) 4/83 (4.8%) 2/33 (6.1%) 1/18 (5.6%) 0/18 (0%)
    Aspartate aminotransferase increased 1/24 (4.2%) 6/83 (7.2%) 2/33 (6.1%) 2/18 (11.1%) 0/18 (0%)
    Bacterial test positive 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Blood alkaline phosphatase increased 1/24 (4.2%) 6/83 (7.2%) 1/33 (3%) 3/18 (16.7%) 1/18 (5.6%)
    Blood bilirubin increased 1/24 (4.2%) 8/83 (9.6%) 0/33 (0%) 3/18 (16.7%) 2/18 (11.1%)
    Blood creatinine increased 3/24 (12.5%) 11/83 (13.3%) 3/33 (9.1%) 3/18 (16.7%) 0/18 (0%)
    Blood lactate dehydrogenase increased 0/24 (0%) 7/83 (8.4%) 5/33 (15.2%) 2/18 (11.1%) 3/18 (16.7%)
    Blood urea increased 3/24 (12.5%) 5/83 (6%) 3/33 (9.1%) 2/18 (11.1%) 1/18 (5.6%)
    Blood uric acid increased 0/24 (0%) 3/83 (3.6%) 2/33 (6.1%) 1/18 (5.6%) 0/18 (0%)
    Brain natriuretic peptide increased 0/24 (0%) 0/83 (0%) 2/33 (6.1%) 0/18 (0%) 0/18 (0%)
    Breath sounds abnormal 2/24 (8.3%) 4/83 (4.8%) 6/33 (18.2%) 2/18 (11.1%) 1/18 (5.6%)
    Ejection fraction decreased 0/24 (0%) 0/83 (0%) 1/33 (3%) 0/18 (0%) 1/18 (5.6%)
    Electrocardiogram QT prolonged 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 1/18 (5.6%)
    Gamma-glutamyltransferase increased 0/24 (0%) 8/83 (9.6%) 4/33 (12.1%) 2/18 (11.1%) 1/18 (5.6%)
    Haptoglobin increased 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Heart rate irregular 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    International normalised ratio increased 1/24 (4.2%) 7/83 (8.4%) 2/33 (6.1%) 2/18 (11.1%) 1/18 (5.6%)
    Neutrophil count decreased 1/24 (4.2%) 6/83 (7.2%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Occult blood positive 1/24 (4.2%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Platelet count decreased 4/24 (16.7%) 4/83 (4.8%) 0/33 (0%) 2/18 (11.1%) 0/18 (0%)
    Pulmonary percussion test abnormality 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Urine analysis abnormal 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Urine bilirubin increased 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Urine ketone body present 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Urine leukocyte esterase positive 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Urine output decreased 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Urine output increased 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Urobilinogen urine increased 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Vitamin D decreased 0/24 (0%) 0/83 (0%) 2/33 (6.1%) 1/18 (5.6%) 0/18 (0%)
    Weight decreased 4/24 (16.7%) 16/83 (19.3%) 3/33 (9.1%) 4/18 (22.2%) 3/18 (16.7%)
    Weight increased 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 1/18 (5.6%)
    White blood cell count decreased 2/24 (8.3%) 10/83 (12%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    White blood cell count increased 3/24 (12.5%) 3/83 (3.6%) 2/33 (6.1%) 1/18 (5.6%) 1/18 (5.6%)
    White blood cells urine positive 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Metabolism and nutrition disorders
    Cachexia 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Decreased appetite 10/24 (41.7%) 42/83 (50.6%) 15/33 (45.5%) 8/18 (44.4%) 7/18 (38.9%)
    Dehydration 4/24 (16.7%) 31/83 (37.3%) 6/33 (18.2%) 3/18 (16.7%) 5/18 (27.8%)
    Fluid overload 0/24 (0%) 0/83 (0%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Fluid retention 0/24 (0%) 0/83 (0%) 4/33 (12.1%) 1/18 (5.6%) 0/18 (0%)
    Hyperglycaemia 1/24 (4.2%) 6/83 (7.2%) 2/33 (6.1%) 0/18 (0%) 0/18 (0%)
    Hyperkalaemia 0/24 (0%) 0/83 (0%) 1/33 (3%) 2/18 (11.1%) 1/18 (5.6%)
    Hyperuricaemia 0/24 (0%) 6/83 (7.2%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Hypoalbuminaemia 1/24 (4.2%) 9/83 (10.8%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Hypocalcaemia 0/24 (0%) 7/83 (8.4%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Hypoglycaemia 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Hypokalaemia 6/24 (25%) 20/83 (24.1%) 8/33 (24.2%) 7/18 (38.9%) 1/18 (5.6%)
    Hypomagnesaemia 2/24 (8.3%) 6/83 (7.2%) 2/33 (6.1%) 1/18 (5.6%) 0/18 (0%)
    Hyponatraemia 3/24 (12.5%) 12/83 (14.5%) 6/33 (18.2%) 1/18 (5.6%) 3/18 (16.7%)
    Hypophosphataemia 1/24 (4.2%) 5/83 (6%) 3/33 (9.1%) 1/18 (5.6%) 0/18 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 7/24 (29.2%) 10/83 (12%) 7/33 (21.2%) 4/18 (22.2%) 1/18 (5.6%)
    Back pain 7/24 (29.2%) 11/83 (13.3%) 5/33 (15.2%) 3/18 (16.7%) 3/18 (16.7%)
    Bone pain 5/24 (20.8%) 3/83 (3.6%) 3/33 (9.1%) 1/18 (5.6%) 0/18 (0%)
    Muscle spasms 2/24 (8.3%) 2/83 (2.4%) 3/33 (9.1%) 1/18 (5.6%) 1/18 (5.6%)
    Muscular weakness 3/24 (12.5%) 6/83 (7.2%) 3/33 (9.1%) 1/18 (5.6%) 1/18 (5.6%)
    Musculoskeletal chest pain 0/24 (0%) 5/83 (6%) 2/33 (6.1%) 1/18 (5.6%) 1/18 (5.6%)
    Musculoskeletal pain 3/24 (12.5%) 8/83 (9.6%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Myalgia 8/24 (33.3%) 8/83 (9.6%) 5/33 (15.2%) 6/18 (33.3%) 2/18 (11.1%)
    Neck pain 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Pain in extremity 5/24 (20.8%) 1/83 (1.2%) 4/33 (12.1%) 3/18 (16.7%) 1/18 (5.6%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Skin papilloma 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Tumour pain 0/24 (0%) 1/83 (1.2%) 2/33 (6.1%) 0/18 (0%) 0/18 (0%)
    Nervous system disorders
    Balance disorder 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Cognitive disorder 2/24 (8.3%) 3/83 (3.6%) 0/33 (0%) 0/18 (0%) 0/18 (0%)
    Dizziness 11/24 (45.8%) 17/83 (20.5%) 2/33 (6.1%) 2/18 (11.1%) 2/18 (11.1%)
    Dysgeusia 1/24 (4.2%) 6/83 (7.2%) 6/33 (18.2%) 1/18 (5.6%) 1/18 (5.6%)
    Extensor plantar response 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Headache 3/24 (12.5%) 14/83 (16.9%) 1/33 (3%) 5/18 (27.8%) 3/18 (16.7%)
    Hyporeflexia 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Lethargy 1/24 (4.2%) 3/83 (3.6%) 1/33 (3%) 0/18 (0%) 1/18 (5.6%)
    Nerve compression 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Neuralgia 0/24 (0%) 3/83 (3.6%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Neuropathy peripheral 7/24 (29.2%) 1/83 (1.2%) 7/33 (21.2%) 2/18 (11.1%) 1/18 (5.6%)
    Peripheral motor neuropathy 3/24 (12.5%) 9/83 (10.8%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Peripheral sensory neuropathy 4/24 (16.7%) 2/83 (2.4%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Peroneal nerve palsy 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Restless leg syndrome 2/24 (8.3%) 1/83 (1.2%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Sciatica 0/24 (0%) 0/83 (0%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Sinus headache 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Tardive dyskinesia 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Tremor 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    VIIth nerve paralysis 0/24 (0%) 5/83 (6%) 1/33 (3%) 0/18 (0%) 1/18 (5.6%)
    Psychiatric disorders
    Anxiety 1/24 (4.2%) 7/83 (8.4%) 2/33 (6.1%) 3/18 (16.7%) 0/18 (0%)
    Confusional state 1/24 (4.2%) 7/83 (8.4%) 3/33 (9.1%) 1/18 (5.6%) 1/18 (5.6%)
    Depression 4/24 (16.7%) 2/83 (2.4%) 6/33 (18.2%) 2/18 (11.1%) 0/18 (0%)
    Hallucination 1/24 (4.2%) 1/83 (1.2%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Insomnia 1/24 (4.2%) 10/83 (12%) 1/33 (3%) 0/18 (0%) 3/18 (16.7%)
    Mental status changes 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Renal and urinary disorders
    Dysuria 1/24 (4.2%) 2/83 (2.4%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Haematuria 1/24 (4.2%) 4/83 (4.8%) 0/33 (0%) 1/18 (5.6%) 1/18 (5.6%)
    Hydronephrosis 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Micturition urgency 1/24 (4.2%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Pollakiuria 2/24 (8.3%) 2/83 (2.4%) 0/33 (0%) 2/18 (11.1%) 0/18 (0%)
    Renal failure 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Renal failure acute 0/24 (0%) 3/83 (3.6%) 2/33 (6.1%) 1/18 (5.6%) 1/18 (5.6%)
    Urinary tract obstruction 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Reproductive system and breast disorders
    Genital rash 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Pelvic pain 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Perineal pain 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Vaginal inflammation 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 2/18 (11.1%) 0/18 (0%)
    Bronchial fistula 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Cough 6/24 (25%) 13/83 (15.7%) 4/33 (12.1%) 3/18 (16.7%) 7/18 (38.9%)
    Dysphonia 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Dyspnoea 6/24 (25%) 19/83 (22.9%) 7/33 (21.2%) 5/18 (27.8%) 5/18 (27.8%)
    Dyspnoea exertional 6/24 (25%) 8/83 (9.6%) 4/33 (12.1%) 2/18 (11.1%) 2/18 (11.1%)
    Epistaxis 6/24 (25%) 2/83 (2.4%) 3/33 (9.1%) 0/18 (0%) 0/18 (0%)
    Haemoptysis 0/24 (0%) 2/83 (2.4%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Hiccups 0/24 (0%) 4/83 (4.8%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Hypoventilation 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Hypoxia 0/24 (0%) 2/83 (2.4%) 2/33 (6.1%) 1/18 (5.6%) 0/18 (0%)
    Laryngeal inflammation 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Lung infiltration 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Nasal congestion 1/24 (4.2%) 2/83 (2.4%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Oropharyngeal pain 3/24 (12.5%) 6/83 (7.2%) 5/33 (15.2%) 1/18 (5.6%) 0/18 (0%)
    Pleural effusion 1/24 (4.2%) 2/83 (2.4%) 3/33 (9.1%) 5/18 (27.8%) 1/18 (5.6%)
    Pneumonitis 1/24 (4.2%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Pneumothorax 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Productive cough 0/24 (0%) 2/83 (2.4%) 2/33 (6.1%) 1/18 (5.6%) 2/18 (11.1%)
    Pulmonary embolism 0/24 (0%) 5/83 (6%) 2/33 (6.1%) 1/18 (5.6%) 0/18 (0%)
    Pulmonary haemorrhage 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Rales 1/24 (4.2%) 5/83 (6%) 1/33 (3%) 1/18 (5.6%) 1/18 (5.6%)
    Respiratory failure 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Rhinitis allergic 1/24 (4.2%) 1/83 (1.2%) 1/33 (3%) 0/18 (0%) 1/18 (5.6%)
    Rhonchi 3/24 (12.5%) 3/83 (3.6%) 1/33 (3%) 1/18 (5.6%) 1/18 (5.6%)
    Sinus congestion 2/24 (8.3%) 1/83 (1.2%) 0/33 (0%) 3/18 (16.7%) 0/18 (0%)
    Sputum discoloured 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Wheezing 3/24 (12.5%) 4/83 (4.8%) 2/33 (6.1%) 2/18 (11.1%) 0/18 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 14/24 (58.3%) 34/83 (41%) 8/33 (24.2%) 0/18 (0%) 3/18 (16.7%)
    Blister 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Decubitus ulcer 0/24 (0%) 2/83 (2.4%) 3/33 (9.1%) 1/18 (5.6%) 0/18 (0%)
    Dermal cyst 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Dermatitis 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 1/18 (5.6%)
    Dry skin 3/24 (12.5%) 7/83 (8.4%) 2/33 (6.1%) 0/18 (0%) 3/18 (16.7%)
    Erythema 0/24 (0%) 1/83 (1.2%) 2/33 (6.1%) 0/18 (0%) 1/18 (5.6%)
    Hyperhidrosis 3/24 (12.5%) 4/83 (4.8%) 2/33 (6.1%) 2/18 (11.1%) 0/18 (0%)
    Nail discolouration 0/24 (0%) 0/83 (0%) 2/33 (6.1%) 0/18 (0%) 0/18 (0%)
    Onychomadesis 1/24 (4.2%) 0/83 (0%) 2/33 (6.1%) 0/18 (0%) 0/18 (0%)
    Pain of skin 2/24 (8.3%) 2/83 (2.4%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Palmar-plantar erythrodysaesthesia syndrome 0/24 (0%) 0/83 (0%) 2/33 (6.1%) 0/18 (0%) 2/18 (11.1%)
    Petechiae 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Pruritus 3/24 (12.5%) 9/83 (10.8%) 3/33 (9.1%) 2/18 (11.1%) 0/18 (0%)
    Pruritus generalised 0/24 (0%) 0/83 (0%) 1/33 (3%) 1/18 (5.6%) 0/18 (0%)
    Rash 5/24 (20.8%) 16/83 (19.3%) 4/33 (12.1%) 4/18 (22.2%) 2/18 (11.1%)
    Rash follicular 0/24 (0%) 1/83 (1.2%) 1/33 (3%) 0/18 (0%) 1/18 (5.6%)
    Rash macular 1/24 (4.2%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Rash maculo-papular 0/24 (0%) 5/83 (6%) 0/33 (0%) 2/18 (11.1%) 0/18 (0%)
    Rash pruritic 1/24 (4.2%) 2/83 (2.4%) 1/33 (3%) 1/18 (5.6%) 1/18 (5.6%)
    Skin discolouration 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Skin disorder 0/24 (0%) 0/83 (0%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Skin exfoliation 0/24 (0%) 0/83 (0%) 3/33 (9.1%) 2/18 (11.1%) 2/18 (11.1%)
    Skin hyperpigmentation 1/24 (4.2%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 2/18 (11.1%)
    Skin hypertrophy 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Vascular disorders
    Deep vein thrombosis 1/24 (4.2%) 4/83 (4.8%) 1/33 (3%) 1/18 (5.6%) 3/18 (16.7%)
    Flushing 4/24 (16.7%) 2/83 (2.4%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Hot flush 0/24 (0%) 5/83 (6%) 0/33 (0%) 0/18 (0%) 1/18 (5.6%)
    Hypertension 0/24 (0%) 1/83 (1.2%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)
    Hypotension 3/24 (12.5%) 12/83 (14.5%) 6/33 (18.2%) 2/18 (11.1%) 4/18 (22.2%)
    Orthostatic hypotension 2/24 (8.3%) 2/83 (2.4%) 1/33 (3%) 0/18 (0%) 0/18 (0%)
    Pallor 0/24 (0%) 0/83 (0%) 0/33 (0%) 1/18 (5.6%) 0/18 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

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

    Results Point of Contact

    Name/Title Vice President, Clinical Research
    Organization TetraLogic Pharmaceuticals
    Phone 610-889-9900 ext 141
    Email Jeffrey.Skolnik@tetralogicpharma.com
    Responsible Party:
    TetraLogic Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01188499
    Other Study ID Numbers:
    • TL32711-POC-0078-PTL
    First Posted:
    Aug 25, 2010
    Last Update Posted:
    May 30, 2016
    Last Verified:
    Apr 1, 2016