Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39211   clinical trials with a EudraCT protocol, of which   6426   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 1 Trial of PF-03084014 in Patients With Advanced Solid Tumor Malignancy and T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma

    Summary
    EudraCT number
    2010-022036-36
    Trial protocol
    IT  
    Global end of trial date
    22 Nov 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    10 Nov 2017
    First version publication date
    10 Nov 2017
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    A8641014
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00878189
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer, Inc.
    Sponsor organisation address
    235 E 42nd Street, New York, United States, 10017
    Public contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer ClinicalTrials.gov Call Center, 001 800781021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer ClinicalTrials.gov Call Center, Pfizer, Inc., 001 8007181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 May 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    10 Jan 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Nov 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objectives of this trial were: 1. To determine the maximum tolerated dose (MTD); and 2. To define the recommended phase 2 dose (RP2D) of PF-03084014 when administered twice daily (BID) for 21 days alone in patients with advanced malignancies.
    Protection of trial subjects
    The study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. In addition, all local regulatory requirements were followed, in particular, those affording greater protection to the safety of trial subjects.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    25 Jun 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United States: 68
    Country: Number of subjects enrolled
    Italy: 4
    Worldwide total number of subjects
    72
    EEA total number of subjects
    4
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    51
    From 65 to 84 years
    21
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    This study originally planned to give PF-03084014 in combination with dexamethasone in subjects with solid tumors and with T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma, including a drug-drug-interaction test of PF-03084014 and dexamethasone in solid tumor participants. But these parts were removed per protocol amendments.

    Pre-assignment
    Screening details
    This study was conducted in male or female with age greater than or equal to 16, and with advanced malignancies (encompassing solid tumors and refractory/ relapsed T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma [T-ALL/ LBL]). Female who were pregnant or giving breast feeding had been excluded.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    PF-03084014 20 mg BID in Solid Tumor Subjects
    Arm description
    PF-03084014 20 mg was administered BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of pharmacokinetic (PK) assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-03084014
    Investigational medicinal product code
    PF-03081014
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    PF-03084014 20 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Arm title
    PF-03084014 40 mg BID in Solid Tumor Subjects
    Arm description
    PF-03084014 40 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-03084014
    Investigational medicinal product code
    PF-03084014
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    PF-03084014 40 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Arm title
    PF-03084014 80 mg BID in Solid Tumor Subjects
    Arm description
    PF-03084014 80 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-03084014
    Investigational medicinal product code
    PF-03084014
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    PF-03084014 80 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Arm title
    PF-03084014 100 mg BID in Solid Tumor Subjects
    Arm description
    PF-03084014 100 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously..
    Arm type
    Experimental

    Investigational medicinal product name
    PF-03084014
    Investigational medicinal product code
    PF-03084014
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    PF-03084014 100 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Arm title
    PF-03084014 130 mg BID in Solid Tumor Subjects
    Arm description
    PF-03084014 130 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously..
    Arm type
    Experimental

    Investigational medicinal product name
    PF-03084014
    Investigational medicinal product code
    PF-03084014
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    PF-03084014 130 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Arm title
    PF-03084014 150 mg BID in Solid Tumor Subjects
    Arm description
    PF-03084014 150 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-03084014
    Investigational medicinal product code
    PF-03084014
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    PF-03084014 150 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Arm title
    PF-03084014 220 mg BID in Solid Tumor Subjects
    Arm description
    PF-03084014 220 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-03084014
    Investigational medicinal product code
    PF-03084014
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    PF-03084014 220 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Arm title
    PF-03084014 330 mg BID in Solid Tumor Subjects
    Arm description
    PF-03084014 330 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-03084014
    Investigational medicinal product code
    PF-03084014
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    PF-03084014 330 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Arm title
    PF-03084014 in T-ALL/LBL Subjects
    Arm description
    PF-03084014 150 mg was administered orally BID to subjects with T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) as single agent for 21 days per cycle continuously (except for Cycle 1). On Cycle 1 Day 21, only the morning dose was administered, followed by a 7-day washout interval.
    Arm type
    Experimental

    Investigational medicinal product name
    PF-03081014
    Investigational medicinal product code
    PF-03081014
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    PF-03084014 150 mg was administered orally BID to subjects with T-ALL/LBL as single agent for 21 days per cycle continuously (except for Cycle 1). On Cycle 1 Day 21, only the morning dose was administered, followed by a 7-day washout interval.

    Number of subjects in period 1
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Started
    3
    3
    4
    8
    4
    23
    16
    3
    8
    Completed
    0
    0
    0
    0
    0
    0
    0
    0
    0
    Not completed
    3
    3
    4
    8
    4
    23
    16
    3
    8
         Subject Refused Further Follow-up
    -
    -
    4
    -
    -
    4
    -
    -
    -
         Objective progression or relapse
    -
    -
    -
    -
    -
    -
    -
    -
    3
         Adverse event, serious fatal
    -
    1
    -
    1
    -
    -
    -
    -
    1
         Unspecified
    3
    2
    -
    7
    4
    18
    15
    3
    4
         Lost to follow-up
    -
    -
    -
    -
    -
    1
    1
    -
    -

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Study
    Reporting group description
    -

    Reporting group values
    Overall Study Total
    Number of subjects
    72 72
    Age categorical
    Units: Subjects
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    51 51
        From 65-84 years
    21 21
        85 years and over
    0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    52.9 ± 16.1 -
    Gender, Male/Female
    Units: Subjects
        Female
    35 35
        Male
    37 37
    Subject analysis sets

    Subject analysis set title
    PF-03084014 in T-ALL/LBL Subjects
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    PF-03084014 150 mg was administered orally BID to subjects with T-ALL/LBL as single agent for 21 days per cycle continuously (except for Cycle 1). On Cycle 1 Day 21, only the morning dose was administered, followed by a 7-day washout interval.

    Subject analysis set title
    PF-03084014 in Solid Tumor Subjects
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    PF-03084014 20, 40, 80, 100, 130, 150, 220 and 330 mg was administered orally BID to subjects with advanced solid tumor malignancies as single agent for 21 days per cycle continuously (except for Cycle 1). On Cycle 1 Day 21, only the morning dose was administered, followed by a 7-day washout interval.

    Subject analysis sets values
    PF-03084014 in T-ALL/LBL Subjects PF-03084014 in Solid Tumor Subjects
    Number of subjects
    8
    64
    Age categorical
    Units: Subjects
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    0
    0
        Adults (18-64 years)
    8
    43
        From 65-84 years
    0
    21
        85 years and over
    0
    0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    30.8 ± 9.0
    55.6 ± 14.7
    Gender, Male/Female
    Units: Subjects
        Female
    2
    33
        Male
    6
    31

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    PF-03084014 20 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 20 mg was administered BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of pharmacokinetic (PK) assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Reporting group title
    PF-03084014 40 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 40 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Reporting group title
    PF-03084014 80 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 80 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Reporting group title
    PF-03084014 100 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 100 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously..

    Reporting group title
    PF-03084014 130 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 130 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously..

    Reporting group title
    PF-03084014 150 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 150 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Reporting group title
    PF-03084014 220 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 220 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Reporting group title
    PF-03084014 330 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 330 mg was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, subjects with advanced solid tumor malignancies received PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was administered BID continuously.

    Reporting group title
    PF-03084014 in T-ALL/LBL Subjects
    Reporting group description
    PF-03084014 150 mg was administered orally BID to subjects with T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL) as single agent for 21 days per cycle continuously (except for Cycle 1). On Cycle 1 Day 21, only the morning dose was administered, followed by a 7-day washout interval.

    Subject analysis set title
    PF-03084014 in T-ALL/LBL Subjects
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    PF-03084014 150 mg was administered orally BID to subjects with T-ALL/LBL as single agent for 21 days per cycle continuously (except for Cycle 1). On Cycle 1 Day 21, only the morning dose was administered, followed by a 7-day washout interval.

    Subject analysis set title
    PF-03084014 in Solid Tumor Subjects
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    PF-03084014 20, 40, 80, 100, 130, 150, 220 and 330 mg was administered orally BID to subjects with advanced solid tumor malignancies as single agent for 21 days per cycle continuously (except for Cycle 1). On Cycle 1 Day 21, only the morning dose was administered, followed by a 7-day washout interval.

    Primary: Number of Solid Tumor Subjects With First-Cycle Dose-Limiting Toxicity (DLT)

    Close Top of page
    End point title
    Number of Solid Tumor Subjects With First-Cycle Dose-Limiting Toxicity (DLT) [1] [2]
    End point description
    Any DLT event attributable to PF-03084014 during Cycle 1: non-hematologic toxicities >= Grade 3 despite optimal care; treatment delay >=7 days or unable to deliver at least 80% of planned dose due to treatment-related toxicities; Grade 4 neutropenia >7 days; febrile neutropenia; neutropenic infection; Grade >=3 thrombocytopenia with bleeding. Analysis population included solid tumor subjects enrolled for dose-escalation who started treatment and who did not have first cycle major treatment deviations (including less than 80% of the planned dose of PF-03084014 in Cycle 1 for reasons other than treatment-related toxicities) were evaluable for DLTs.
    End point type
    Primary
    End point timeframe
    Baseline to the end of Cycle 1 (Week 4)
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint only applies to solid tumor subjects.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint only applies to solid tumor subjects.
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    3
    3
    3
    6
    3
    6
    6
    2
    Units: subjects
    0
    0
    0
    1
    0
    1
    1
    2
    No statistical analyses for this end point

    Primary: Number of T-ALL/LBL Subjects With First-Cycle DLT

    Close Top of page
    End point title
    Number of T-ALL/LBL Subjects With First-Cycle DLT [3] [4]
    End point description
    Any dose-limiting toxicity (DLT) attributable to PF-03084014 at 1st Cycle: non-hematologic toxicities >= Grade 3 despite optimal care; treatment delay >=7 days; unable to deliver at least 80% of planned dose; absolute neutrophil count (ANC) <1000/microliter (uL), or platelet count <30,000/uL, or hemoglobin <8 gram/deciliter (g/dL) in a bone marrow with <5% blasts and no evidence of leukemia or abnormal dysplasia for >42 days. Analysis population included T-ALL/LBL subjects enrolled for dose-escalation who started treatment and who did not have first cycle major treatment deviations (including less than 80% of the planned dose of PF-03084014 in Cycle 1 for reasons other than treatment-related toxicities) were evaluable for DLTs.
    End point type
    Primary
    End point timeframe
    Baseline to the end of Cycle 1 (Week 4)
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This endpoint only applies to T-ALL/LBL subjects
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint only applies to T-ALL/LBL subjects
    End point values
    PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    5
    Units: subjects
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) (All Causality)

    Close Top of page
    End point title
    Number of Subjects With Treatment-Emergent Adverse Events (TEAEs) (All Causality)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of casual relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious adverse event (SAE) was any untoward medical occurrence at any dose that: Resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), and resulted in congenital anomaly/birth defect. Analysis population included all subjects who received at least 1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline to the end of study (28 days after last dose of study drug)
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    4
    8
    4
    23
    16
    3
    8
    Units: subjects
        No. of Subjects With AEs
    3
    3
    4
    6
    4
    23
    16
    3
    8
        No. of Subjects With SAEs
    1
    1
    2
    4
    2
    8
    7
    1
    4
        No. of Subjects Discontinued PF-03084014
    0
    1
    0
    2
    1
    1
    4
    2
    3
        No. of Subjects Temp. Discontinued Treatment
    1
    1
    2
    1
    1
    9
    5
    1
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With TEAEs (Treatment-Related)

    Close Top of page
    End point title
    Number of Subjects With TEAEs (Treatment-Related)
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug. Treatment-related events were those assessed by the investigator as related to study medication. An SAE was any untoward medical occurrence at any dose that: Resulted in death, was life-threatening (immediate risk of death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), and resulted in congenital anomaly/birth defect. Analysis population included all subjects who received at least 1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline to the end of study (28 days after last dose of study drug).
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    4
    8
    4
    23
    16
    3
    8
    Units: subjects
        No. of Subjects With AEs
    2
    1
    2
    6
    4
    20
    16
    3
    5
        No. of Subjects With SAEs
    0
    0
    0
    1
    1
    0
    1
    0
    1
        No. of Subjects Discontinued PF-03084014
    0
    0
    0
    1
    0
    1
    1
    1
    0
        No. of Subjects Temp. Discontinued Treatment
    0
    0
    0
    0
    1
    7
    4
    1
    0
        No.of Subjects With Dose Reduction Due to AEs
    0
    0
    0
    0
    1
    4
    3
    1
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) (All Causality) by maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade

    Close Top of page
    End point title
    Number of Subjects with Treatment-Emergent Adverse Events (TEAEs) (All Causality) by maximum Common Terminology Criteria for Adverse Events (CTCAE) Grade
    End point description
    An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. CTCAE version 3.0 was used for AE grading: Grade 1 mild AE; Grade 2 moderate AE; Grade 3 severe AE; Grade 4 life-threatening or disabling AE; Grade 5 death related to AE. Analysis population included all subjects who received at least 1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline to the end of study (28 days after last dose of study drug)
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    4
    8
    4
    23
    16
    3
    8
    Units: subjects
        Any AEs, Grade 1
    0
    0
    1
    0
    0
    1
    1
    0
    1
        Any AEs, Grade 2
    2
    1
    0
    1
    2
    8
    3
    0
    1
        Any AEs, Grade 3
    1
    1
    2
    2
    2
    12
    9
    2
    4
        Any AEs, Grade 4
    0
    0
    1
    2
    0
    2
    1
    1
    1
        Any AEs, Grade 5
    0
    1
    0
    1
    0
    0
    2
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects with TEAEs (Treatment-Related) by Maximum CTCAE Grade

    Close Top of page
    End point title
    Number of Subjects with TEAEs (Treatment-Related) by Maximum CTCAE Grade
    End point description
    An AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. Treatment-related events were those assessed by the investigator as related to study medication. CTCAE version 3.0 was used for AE grading: Grade 1 mild AE; Grade 2 moderate AE; Grade 3 severe AE; Grade 4 life-threatening or disabling AE; Grade 5 death related to AE. Analysis population included all subjects who received at least 1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline to the end of study (28 days after last dose of study drug)
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    4
    8
    4
    23
    16
    3
    8
    Units: Subjects
        Any AEs, Grade 1
    1
    0
    1
    1
    1
    6
    2
    0
    3
        Any AEs, Grade 2
    1
    1
    0
    3
    2
    6
    4
    1
    0
        Any AEs, Grade 3
    0
    0
    1
    1
    1
    8
    10
    2
    1
        Any AEs, Grade 4
    0
    0
    0
    1
    0
    0
    0
    0
    0
        Any AEs, Grade 5
    0
    0
    0
    0
    0
    0
    0
    0
    0
        Missing or Unknown
    0
    0
    0
    0
    0
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of Subjects With Potentially Clinical Significant Categorical Changes From Baseline in Electrocardiogram (ECG) Findings in QTc Interval

    Close Top of page
    End point title
    Number of Subjects With Potentially Clinical Significant Categorical Changes From Baseline in Electrocardiogram (ECG) Findings in QTc Interval
    End point description
    Criteria for potentially important changes in ECG were defined as: maximum (max.) post-dose (post-baseline) time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole (QT interval) corrected for heart rate using Fridericia's formular (QTcF), or QT interval corrected for heart rate using Bazett's formula (QTcB): <450, 450 -<480, 480-<500, and >=500 msec. Maximum increase (inc.) from baseline in QTcF or QTcB: change (chg) <30, 30=<chg<60, and chg >=60 msec. Analysis population included all subjects who received at least 1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline to end of study treatment (Day 28).
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    4
    8
    4
    23
    16
    3
    8
    Units: subjects
        Max. QTcB interval <450
    0
    3
    2
    4
    2
    11
    5
    2
    8
        Max. QTcB interval 450-<480
    3
    0
    1
    3
    2
    8
    9
    1
    0
        Max. QTcB interval 480-<500
    0
    0
    0
    1
    0
    4
    0
    0
    0
        Max. QTcB interval >=500
    0
    0
    1
    0
    0
    0
    2
    0
    0
        Max. QTcF interval <450
    3
    3
    2
    7
    3
    13
    12
    3
    8
        Max. QTcF interval 450-<480
    0
    0
    1
    0
    1
    9
    2
    0
    0
        Max. QTcF interval 480-<500
    0
    0
    0
    1
    0
    1
    0
    0
    0
        Max. QTcF interval >=500
    0
    0
    1
    0
    0
    0
    2
    0
    0
        Max. QTcB interval inc. from baseline chg<30
    1
    2
    1
    7
    3
    21
    7
    3
    7
        Max. QTcB interval inc. from baseline 30=<chg<60
    2
    1
    2
    1
    1
    2
    7
    0
    1
        Max. QTcB interval inc. from baseline chg>=60
    0
    0
    1
    0
    0
    0
    2
    0
    0
        Max. QTcF interval inc. from baseline chg<30
    3
    2
    1
    7
    3
    22
    12
    3
    8
        Max. QTcF interval inc. from baseline 30=<chg<60
    0
    1
    2
    1
    1
    1
    2
    0
    0
        Max. QTcF interval inc. from baseline chg>=60
    0
    0
    1
    0
    0
    0
    2
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Subjects With Laboratory Tests Abnormalities Meeting the Criteria of Potential Clinical Concern (Hematology and Chemistries, All Cycles)

    Close Top of page
    End point title
    Number of Subjects With Laboratory Tests Abnormalities Meeting the Criteria of Potential Clinical Concern (Hematology and Chemistries, All Cycles)
    End point description
    Parameters analyzed included: White blood cell (WBC) count plus differential, absolute (Abs) neutrophil count, platelets, hemoglobin, sodium, potassium, bicarbonate, chloride, blood urea nitrogen, creatinine, glucose, uric acid, calcium, phosphate, magnesium, total protein, albumin, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), partial prothrombin time/international normalized ratio (PTT/INR). Urinalysis: pH, specific gravity, protein, glucose, ketones, blood, leukocyte esterase, and nitrites. Pregnancy test: Serum or urine pregnancy test for women of childbearing potential. There were no changes in urine protein among the solid tumor and T-ALL/LBL subjects that were clinically significant. Clinical significance was judged by the investigator. Analysis population included all subjects who received at least 1 dose of study medication.
    End point type
    Secondary
    End point timeframe
    Baseline to the end of study (28 days after last dose of study drug).
    End point values
    PF-03084014 in T-ALL/LBL Subjects PF-03084014 in Solid Tumor Subjects
    Number of subjects analysed
    8
    64
    Units: subjects
        Hemoglobin
    8
    45
        Lymphocytes (abs)
    8
    40
        Neutrophils (abs)
    5
    4
        Platelets
    6
    13
        WBC
    5
    4
        ALT
    4
    22
        ALP
    3
    24
        AST
    4
    32
        Bicarbonate
    1
    15
        Bilirubin
    2
    10
        Creatinine
    1
    17
        Hypercalcaemia
    0
    2
        Hyperglycaemia
    6
    55
        Hyperkalaemia
    0
    4
        Hypermagnesaemia
    0
    1
        Hypernatraemia
    0
    4
        Hypoalbuminaemia
    6
    43
        Hypocalcaemia
    6
    18
        Hypoglycaemia
    0
    6
        Hypokalaemia
    4
    23
        Hypomagnesaemia
    1
    8
        Hyponatraemia
    3
    19
        Hypophosphataemia
    4
    54
    No statistical analyses for this end point

    Secondary: Maximum Observed Serum Concentration (Cmax) After a Single Dose on Cycle 1 Day 1

    Close Top of page
    End point title
    Maximum Observed Serum Concentration (Cmax) After a Single Dose on Cycle 1 Day 1
    End point description
    Cmax was the maximum observed serum concentration. Analysis population included all treated subjects who had at least 1 of the pharmacokinetic (PK) parameters of interest. N=number of subjects evaluable for this endpoint
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (predose and 0.5, 1, 2, 4, and 10 hours [hr] postdose)
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    4
    8
    4
    22
    16
    3
    8
    Units: nanogram/milliliter (ng/mL)
        geometric mean (geometric coefficient of variation)
    163 ± 62
    368 ± 48
    230 ± 193
    691 ± 37
    536 ± 72
    943 ± 100
    861 ± 63
    1892 ± 54
    1604 ± 85
    No statistical analyses for this end point

    Secondary: Time to Reach Cmax (Tmax) After a Single Dose on Cycle 1 Day 1

    Close Top of page
    End point title
    Time to Reach Cmax (Tmax) After a Single Dose on Cycle 1 Day 1
    End point description
    Tmax was the time to reach maximum serum concentration (Cmax). Analysis population included all treated subjects who had at least 1 of the PK parameters of interest. N=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose)
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    4
    8
    4
    22
    16
    3
    8
    Units: hr
        median (full range (min-max))
    1.0 (0.9 to 1.0)
    1.0 (1.0 to 1.3)
    2.0 (1.0 to 8.0)
    1.0 (1.0 to 2.0)
    2.5 (1.0 to 4.0)
    1.1 (0.5 to 4.1)
    2.0 (1.0 to 4.1)
    1.2 (1.0 to 2.0)
    1.1 (0.9 to 4.0)
    No statistical analyses for this end point

    Secondary: Area Under the Time-Concentration Curve From Time 0 to the Dosing Interval (AUCtau) After a Single Dose on Cycle 1 Day 1

    Close Top of page
    End point title
    Area Under the Time-Concentration Curve From Time 0 to the Dosing Interval (AUCtau) After a Single Dose on Cycle 1 Day 1
    End point description
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval).99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3. Analysis population included all treated subjects who had at least 1 of the PK parameters of interest. N=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose)
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    3
    7
    3
    21
    16
    2 [5]
    4
    Units: nanogram*hour/milliliter (ng*hr/mL)
        geometric mean (geometric coefficient of variation)
    409 ± 83
    1329 ± 87
    1649 ± 98
    2204 ± 37
    2924 ± 81
    3677 ± 86
    3593 ± 58
    8014 ± 99999
    6412 ± 80
    Notes
    [5] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    No statistical analyses for this end point

    Secondary: Cmax After Multiple Dose on Cycle 1 Day 21

    Close Top of page
    End point title
    Cmax After Multiple Dose on Cycle 1 Day 21 [6]
    End point description
    Cmax was the maximum observed serum concentration. 99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3. Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)
    Notes
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2 [7]
    2 [8]
    3
    5
    3
    12
    8
    4
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    64.5 ± 99999
    381 ± 99999
    313 ± 29
    867 ± 44
    421 ± 130
    1246 ± 79
    1894 ± 76
    1828 ± 42
    Notes
    [7] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    [8] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    No statistical analyses for this end point

    Secondary: Time to Reach Cmax (Tmax) after multiple dose on Cycle 1 Day 21

    Close Top of page
    End point title
    Time to Reach Cmax (Tmax) after multiple dose on Cycle 1 Day 21 [9]
    End point description
    Tmax was the time to reach maximum serum concentration (Cmax). Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)
    Notes
    [9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2
    2
    3
    5
    3
    12
    8
    4
    Units: hr
        median (full range (min-max))
    1.1 (1.0 to 1.1)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 4.0)
    1.1 (1.0 to 2.7)
    3.7 (1.0 to 8.0)
    1.1 (1.0 to 4.0)
    1.0 (0.5 to 2.0)
    1.6 (1.0 to 2.0)
    No statistical analyses for this end point

    Secondary: AUCtau After Multiple Dose on Cycle 1 Day 21

    Close Top of page
    End point title
    AUCtau After Multiple Dose on Cycle 1 Day 21 [10]
    End point description
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). 99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3. Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2 [11]
    2 [12]
    3
    5
    3
    12
    8
    4
    Units: ng*hr/mL
        geometric mean (geometric coefficient of variation)
    309 ± 99999
    2521 ± 99999
    1572 ± 42
    4741 ± 70
    3155 ± 59
    6430 ± 89
    10520 ± 89
    9161 ± 30
    Notes
    [11] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    [12] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    No statistical analyses for this end point

    Secondary: Apparent Volume of Distribution (Vz/F) on Cycle 1 Day 21

    Close Top of page
    End point title
    Apparent Volume of Distribution (Vz/F) on Cycle 1 Day 21 [13]
    End point description
    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired concentration of a drug. 99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3. Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2 [14]
    2 [15]
    2 [16]
    5
    3
    12
    8
    3
    Units: liter (L)
        geometric mean (geometric coefficient of variation)
    2810 ± 99999
    516 ± 99999
    3353 ± 99999
    986 ± 52
    2048 ± 49
    801 ± 144
    852 ± 120
    424 ± 61
    Notes
    [14] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    [15] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    [16] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    No statistical analyses for this end point

    Secondary: Serum Decay Half-Life (t1/2) After Multiple Dose on Cycle 1 Day 21

    Close Top of page
    End point title
    Serum Decay Half-Life (t1/2) After Multiple Dose on Cycle 1 Day 21 [17]
    End point description
    Serum decay half-life is the time measured for the serum concentration to decrease by one half. 99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3. Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2 [18]
    2 [19]
    2 [20]
    5
    3
    12
    8
    3
    Units: hr
        arithmetic mean (standard deviation)
    30.3 ± 99999
    22.6 ± 99999
    38.6 ± 99999
    34.2 ± 11.7
    34.7 ± 5.3
    25.3 ± 9.2
    29.3 ± 9.3
    18.0 ± 3.6
    Notes
    [18] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    [19] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    [20] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    No statistical analyses for this end point

    Secondary: Apparent Oral Clearance (CL/F) on Cycle 1 Day 21

    Close Top of page
    End point title
    Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 [21]
    End point description
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. 99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3 Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2 [22]
    2 [23]
    3
    5
    3
    12
    8
    4
    Units: liter/hour (L/hr)
        geometric mean (geometric coefficient of variation)
    64.8 ± 99999
    15.9 ± 99999
    50.9 ± 42
    21.1 ± 70
    41.2 ± 59
    23.4 ± 88
    20.9 ± 89
    16.4 ± 30
    Notes
    [22] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    [23] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    No statistical analyses for this end point

    Secondary: Minimum Observed Serum Concentration (Cmin) After Multiple Dose on Cycle 1 Day 21

    Close Top of page
    End point title
    Minimum Observed Serum Concentration (Cmin) After Multiple Dose on Cycle 1 Day 21 [24]
    End point description
    Cmin was the minimum observed serum concentration. 99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3. Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (predose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr postdose)
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2 [25]
    2 [26]
    3
    5
    3
    12
    8
    4
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    10.7 ± 99999
    126 ± 99999
    59.2 ± 103
    232 ± 118
    206 ± 40
    266 ± 102
    469 ± 118
    420 ± 81
    Notes
    [25] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    [26] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    No statistical analyses for this end point

    Secondary: Average Serum Concentration (Cavg) at Steady State on Cycle 1 Day 21

    Close Top of page
    End point title
    Average Serum Concentration (Cavg) at Steady State on Cycle 1 Day 21 [27]
    End point description
    Cavg was the average serum concentration at steady state.99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3.Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (predose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr postdose)
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2 [28]
    2 [29]
    3
    5
    3
    12
    8
    4
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    25.7 ± 99999
    210 ± 99999
    131 ± 42
    395 ± 69
    263 ± 59
    536 ± 89
    877 ± 89
    763 ± 30
    Notes
    [28] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    [29] - Geometric %CV was NE when No. of subjects analyzed is <3, hence data was not calculated.
    No statistical analyses for this end point

    Secondary: Accumulation ratio (Rac) on Cycle 1 Day 21

    Close Top of page
    End point title
    Accumulation ratio (Rac) on Cycle 1 Day 21 [30]
    End point description
    Accumulation was calculated as AUCtau at steady state (Cycle 1 Day 21) divided by AUCtau after a single dose on Cycle 1 Day 1. 99999 signifies data not estimable. Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (predose and 0.5, 1, 2, 4, and 10 hr postdose), Cycle 1 Day 21 (predose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr postdose)
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2
    2
    2
    5
    3
    12
    8
    1 [31]
    Units: ratio
        median (full range (min-max))
    1.18 (0.72 to 1.63)
    1.60 (1.45 to 1.74)
    1.36 (0.93 to 1.79)
    2.49 (1.23 to 2.86)
    1.98 (1.81 to 2.15)
    2.29 (0.95 to 4.90)
    2.84 (1.14 to 5.80)
    0.97 (00000 to 99999)
    Notes
    [31] - Unable to calculate median and range as only 1 subject provided value.
    No statistical analyses for this end point

    Secondary: Dose-normalized AUCtau [AUCtau(dn)] in the Fasted State for Solid Tumor Subjects

    Close Top of page
    End point title
    Dose-normalized AUCtau [AUCtau(dn)] in the Fasted State for Solid Tumor Subjects
    End point description
    AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Analysis population included solid tumor subjects who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (predose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (predose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    End point values
    PF-03084014 in Solid Tumor Subjects
    Number of subjects analysed
    11
    Units: (ng*hr/mL)/mg
        geometric mean (geometric coefficient of variation)
    23.71 ± 115
    No statistical analyses for this end point

    Secondary: Dose-normalized AUCtau [AUCtau(dn)] in the Fed State for Solid Tumor Subjects

    Close Top of page
    End point title
    Dose-normalized AUCtau [AUCtau(dn)] in the Fed State for Solid Tumor Subjects
    End point description
    AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Analysis population included solid tumor subjects who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    End point values
    PF-03084014 in Solid Tumor Subjects
    Number of subjects analysed
    11
    Units: (ng*hr/mL)/mg
        geometric mean (geometric coefficient of variation)
    22.54 ± 67
    No statistical analyses for this end point

    Secondary: Dose-normalized Cmax [Cmax(dn)] in the Fasted State for Solid Tumor Subjects

    Close Top of page
    End point title
    Dose-normalized Cmax [Cmax(dn)] in the Fasted State for Solid Tumor Subjects
    End point description
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Analysis population included solid tumor subjects who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    End point values
    PF-03084014 in Solid Tumor Subjects
    Number of subjects analysed
    13
    Units: (ng/mL)/milligram (ng/mL)/mg
        geometric mean (geometric coefficient of variation)
    6.56 ± 106
    No statistical analyses for this end point

    Secondary: Dose-normalized Cmax(dn) in the Fed State for Solid Tumor Subjects

    Close Top of page
    End point title
    Dose-normalized Cmax(dn) in the Fed State for Solid Tumor Subjects
    End point description
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Analysis population included solid tumor subjects who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose) or Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose) and Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    End point values
    PF-03084014 in Solid Tumor Subjects
    Number of subjects analysed
    13
    Units: (ng/mL)/mg
        geometric mean (geometric coefficient of variation)
    5.22 ± 64
    No statistical analyses for this end point

    Secondary: Percentage of Solid Tumor Subjects With Objective Response (OR)

    Close Top of page
    End point title
    Percentage of Solid Tumor Subjects With Objective Response (OR) [32]
    End point description
    OR was defined as confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as >=30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (plus [+] or minus [-] 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to solid tumor subjects only
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    3
    3
    3
    5
    3
    18
    10
    1
    Units: percentage of subjects
        number (confidence interval 95%)
    33.3 (0.8 to 90.6)
    0 (0.0 to 70.8)
    66.7 (9.4 to 99.2)
    0 (0.0 to 52.2)
    0 (0.0 to 70.8)
    5.6 (0.1 to 27.3)
    10.0 (0.3 to 44.5)
    100 (2.5 to 100.0)
    No statistical analyses for this end point

    Secondary: Time to Progression (TTP) for Solid Tumor Subjects

    Close Top of page
    End point title
    Time to Progression (TTP) for Solid Tumor Subjects [33]
    End point description
    Time from Cycle 1 Day 1 to first documentation of disease progression. Progression was defined as per RECIST version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, uneuivocal progression of non-target disease, or the appearance of new lesions. TTP (months) was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30. 99999 signifies data not estimable.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to solid tumor subjects only
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    3 [34]
    3
    4 [35]
    8 [36]
    4
    23
    16
    3 [37]
    Units: months
        median (confidence interval 95%)
    99999 (0.8 to 99999)
    1.2 (1.0 to 2.8)
    99999 (1.7 to 99999)
    3.1 (1.0 to 99999)
    4.3 (1.6 to 19.5)
    1.6 (1.4 to 6.0)
    1.5 (1.1 to 4.2)
    99999 (99999 to 99999)
    Notes
    [34] - As 2 subjects were censored and only 1 subject was evaluable
    [35] - Unable to calculate as 3 subjects were censored and only 1 subject was evaluable
    [36] - The upper 95% confidence limit can not be calculated due to limited number of subjects
    [37] - Unable to calculate as all 3 subjects were censored
    No statistical analyses for this end point

    Secondary: Duration of Response (DR) for Solid Tumor Subjects

    Close Top of page
    End point title
    Duration of Response (DR) for Solid Tumor Subjects [38]
    End point description
    Time from the first documentation of OR to objective disease progression or death due to any cause. DR was only calculated for subjects with an OR. DR (months) was calculated as (date of first documentation of objective progression or death minus date of first documentation of PR or CR plus 1) divided by 30. 99999 signifies data not estimable.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or -5 days) of every odd cycle or as clinically indicated, up to Cycle 9. Afterwards, assessed on Day 1 (+ or -5 days) every 4 cycles.
    Notes
    [38] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to solid tumor subjects only
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    1 [39]
    2 [40]
    1 [41]
    1 [42]
    1 [43]
    Units: months
        median (confidence interval 95%)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Notes
    [39] - Unable to calculate as the subject was censored.
    [40] - Unable to calculate as the subject was censored.
    [41] - Unable to calculate as the subject was censored.
    [42] - Unable to calculate as the subject was censored.
    [43] - Unable to calculate as the subject was censored.
    No statistical analyses for this end point

    Secondary: Progression-Free Survival (PFS) for Solid Tumor Subjects

    Close Top of page
    End point title
    Progression-Free Survival (PFS) for Solid Tumor Subjects [44]
    End point description
    PFS was defined as the time from Cycle 1 Day 1 to date of first documentation of progression or death due to any cause. Progression was defined as per RECIST version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or target lesions over nadir, unequivocal progression of non-target disease, or the appearance of new lesions. PFS (months) was calculated as (the first event date minus the date of first dose of study medication plus 1) divided by 30. 99999 signifies data not applicable.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9; afterwards assessed on Day 1 (+ or -5 days) every 4 cycles
    Notes
    [44] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to solid tumor subjects only
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    3 [45]
    3
    4 [46]
    8 [47]
    4
    23
    16
    3 [48]
    Units: months
        median (confidence interval 95%)
    99999 (0.8 to 99999)
    1.2 (1.0 to 2.8)
    99999 (1.7 to 99999)
    2.3 (0.4 to 99999)
    4.3 (1.6 to 19.5)
    1.6 (1.4 to 6.0)
    1.5 (1.1 to 4.2)
    99999 (99999 to 99999)
    Notes
    [45] - Unable to calculate as 2 subjects were censored and only 1 subject was evaluable.
    [46] - Unable to calculate as 3 subjects were censored and only 1 subject was evaluable.
    [47] - The upper 95% confidence limit can not be determined due to limited number of subjects with PFS.
    [48] - Unable to calculate as all 3 subjects were censored.
    No statistical analyses for this end point

    Secondary: Percentage of T-ALL/LBL subjects with OR

    Close Top of page
    End point title
    Percentage of T-ALL/LBL subjects with OR [49]
    End point description
    OR was adapted from International Working Group Response Criteria for Acute Myeloid Leukemia (AML). The response categories of interest were CR, complete response with incomplete hematopoietic recovery (CRi), and PR. CR: ANC >1500/microliter (uL), no circulating blasts. Platelets >100,000/uL, <5% marrow blast cells, no extramedullary disease, bone marrow cellularity >20% with tri-lineage hematopoiesis and <5% marrow blast cells, none of which were neoplastic; CRi: same as CR but ANC may be >1500/uL or platelet count >100,000/uL, no requirement on bone marrow cellularity; PR: same as CR but bone marrow with >= 50% reduction of leukemia blast cells and an absolute blast count between 5% and 25%.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9.
    Notes
    [49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to T-ALL/LBL subjects only
    End point values
    PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    8
    Units: percentage of subjects
        number (confidence interval 95%)
    12.5 (0.3 to 52.7)
    No statistical analyses for this end point

    Secondary: Relapse Free Survival (RFS) for T-ALL/LBL subjects

    Close Top of page
    End point title
    Relapse Free Survival (RFS) for T-ALL/LBL subjects [50]
    End point description
    The RFS of CR was defined as the time from the date of first attaining CR to the date of relapse or death from any cause, whichever occurred first. Similarly, the RFS of CR + CRi (or RFS of CR + CRi + partial response [PR]) was defined as the time from the date of first attaining CR + CRi (or CR + CRi + PR) to the date of relapse or death from any cause, whichever occurred first.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9.
    Notes
    [50] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to T-ALL/LBL subjects only
    End point values
    PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    0 [51]
    Units: months
        median (confidence interval 95%)
    ( to )
    Notes
    [51] - Data not analyzed due to halting of T-ALL/LBL subject enrollment and the limited No. of subjects.
    No statistical analyses for this end point

    Secondary: Peripheral Blast Count Reduction (PBR) for T-ALL/LBL Subjects

    Close Top of page
    End point title
    Peripheral Blast Count Reduction (PBR) for T-ALL/LBL Subjects [52]
    End point description
    PBR was the maximum percentage of peripheral blast count reduction for each subject who received at least one dose of study medication. PBR was derived by the Sponsor from percentage of peripheral blood Blast Count reported by sites.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or - 5 days) of every odd cycle or as clinically indicated, up to Cycle 9.
    Notes
    [52] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to T-ALL/LBL subjects only
    End point values
    PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    0 [53]
    Units: percentage of PBR
        number (confidence interval 95%)
    ( to )
    Notes
    [53] - Data not analyzed due to halting of T-ALL/LBL subject enrollment and the limited No. of subjects.
    No statistical analyses for this end point

    Secondary: Changes in Expression Levels of Notch 1 Target Genes in Tumor Biopsies for Solid Tumor Subjects: Hes4 Gene Expression Levels on Cycle 1 Day 21 Relative to That at Baseline

    Close Top of page
    End point title
    Changes in Expression Levels of Notch 1 Target Genes in Tumor Biopsies for Solid Tumor Subjects: Hes4 Gene Expression Levels on Cycle 1 Day 21 Relative to That at Baseline [54]
    End point description
    Gene expression analysis in tumor biopsies was done using cDNA prepared from ribonucleic acid (RNA) extracted from tumor biopsies. Gene expression was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time polymerase chain reaction (PCR) system. Changes from baseline were calculated as ratios to baseline. Only Hes4 gene showed consistent down modulation across dosing cohorts (150 mg and 220 mg BID) and therefore results were reported for Hes4 only.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 1 Day 21 (-5 days)
    Notes
    [54] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to 150 mg BID and 220 mg BID in solid tumor subjects arms only
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    3
    2
    Units: ratio
        arithmetic mean (standard deviation)
    0.9 ± 0.57
    0.5 ± 0.50
    No statistical analyses for this end point

    Secondary: Changes From Baseline in Expression Levels of Notch 1 Target Genes in Peripheral Blood for T-ALL/LBL Subjects: Hes4 Gene Expression Levels on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 21 Relative to That at Baseline

    Close Top of page
    End point title
    Changes From Baseline in Expression Levels of Notch 1 Target Genes in Peripheral Blood for T-ALL/LBL Subjects: Hes4 Gene Expression Levels on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 1 Day 21 Relative to That at Baseline
    End point description
    RNA was extracted from peripheral blood and used as a template to synthesize complementary deoxyribonucleic acid (cDNA). Gene expression in cDNA was measured by custom Taqman low density array (TLDA) cards run on Applied Biosystems 7900HT Fast Real-Time PCR system. Changes from baseline were calculated as ratios to baseline. Results were reported Only for Hes4 as this was the only gene to show consistent down modulation across dosing cohorts (150 mg and 220 mg).
    End point type
    Secondary
    End point timeframe
    Baseline (morning), Cycle 1 Days 8, 15 and 21 (morning, matched with the first PK sample of the particular day), Cycle 1 Day 21 (24, 48, and 120 hr postdose) and at end of treatment (EoT)
    End point values
    PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    8 [55]
    Units: ratio
    arithmetic mean (standard deviation)
        Cycle 1 Day 8, n=7
    0.7 ± 0.65
        Cycle 1 Day 15, n=4
    0.3 ± 0.41
        Cycle 1 Day 21, n=4
    0.4 ± 0.27
        EOT, n=1
    2.0 ± 99999
    Notes
    [55] - Data for standard deviation at EOT was not estimable since only 1 participant was analyzed.
    No statistical analyses for this end point

    Secondary: Changes in Expression Levels of Notch 1 Target Genes in Peripheral Blood for Solid Tumor Subjects: Hairy and Enhancer of Split-4 (Hes4) Gene Expression Level on Cycle 1 Day 8 and Cycle 1 Day 21 Relative to That at Baseline

    Close Top of page
    End point title
    Changes in Expression Levels of Notch 1 Target Genes in Peripheral Blood for Solid Tumor Subjects: Hairy and Enhancer of Split-4 (Hes4) Gene Expression Level on Cycle 1 Day 8 and Cycle 1 Day 21 Relative to That at Baseline [56]
    End point description
    RNA was extracted from peripheral blood and used as a template to synthesize DNA. Gene expression in cDNA was measured by custom TLDA cards run on Applied Biosystems 7900HT Fast Real-Time PCR system. Changes from baseline were calculated as ratios to baseline. Results were reported Only for Hes4 as this was the only gene to show consistent down modulation across dosing cohorts (150 mg and 220 mg).
    End point type
    Secondary
    End point timeframe
    Baseline (morning), Cycle 1 Days 8 and 21 (predose)
    Notes
    [56] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to 150 mg BID and 220 mg BID in solid tumor subjects arms only
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    11
    7
    Units: ratio
    arithmetic mean (standard deviation)
        Cycle 1 Day 8, n=11, 7
    0.3 ± 0.24
    0.1 ± 0.14
        Cycle 1 Day 21, n=6, 5
    0.3 ± 0.33
    0.0 ± 0.02
    No statistical analyses for this end point

    Secondary: Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Peripheral Blood for T-ALL/LBL Subjects

    Close Top of page
    End point title
    Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Peripheral Blood for T-ALL/LBL Subjects [57]
    End point description
    NICD was measured in peripheral blood mononuclear cell (PBMC) pellets using a validated enzyme-linked immunosorbent assay (ELISA). LOQ is the lower limit of quantitation.
    End point type
    Secondary
    End point timeframe
    Baseline, Cycle 1 Days 8 and 15 (predose AM), Cycle 1 Day 21 (predose AM and 24, 48 and 120 hr postdose) and EOT
    Notes
    [57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to T-ALL/LBL subjects only
    End point values
    PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    0 [58]
    Units: optical density
        arithmetic mean (standard deviation)
    ±
    Notes
    [58] - As NICD levels fell below the LOQ of the assay in most cases, No data were reported.
    No statistical analyses for this end point

    Secondary: Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Bone Marrow for T-ALL/LBL Subjects

    Close Top of page
    End point title
    Changes From Baseline in Notch Intracellular Domain (NICD) Levels in Bone Marrow for T-ALL/LBL Subjects [59]
    End point description
    NICD was to be measured in bone marrow mononuclear cell (BMMC) cell pellets using a validated ELISA.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 and Cycles 2 Day 1
    Notes
    [59] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to T-ALL/LBL subjects only
    End point values
    PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    0 [60]
    Units: microgram/milliliter
        arithmetic mean (standard deviation)
    ±
    Notes
    [60] - No. of bone marrow samples received was insufficient and analyses were not mandatory per protocol.
    No statistical analyses for this end point

    Secondary: Dose-normalized Cmax [Cmax (dn)] After a Single Dose on Cycle 1 Day 1

    Close Top of page
    End point title
    Dose-normalized Cmax [Cmax (dn)] After a Single Dose on Cycle 1 Day 1
    End point description
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Analysis population included all treated subjects who had at least 1 of the PK parameters of interest. N=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose)
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    4
    8
    4
    22
    16
    3
    8
    Units: ng/mL/mg
        geometric mean (geometric coefficient of variation)
    8.1 ± 63
    9.2 ± 48
    2.9 ± 193
    6.9 ± 37
    4.1 ± 72
    6.3 ± 100
    3.9 ± 63
    5.7 ± 54
    10.7 ± 85
    No statistical analyses for this end point

    Secondary: Dose-normalized AUCtau [AUCtau (dn) ] After a single dose on Cycle 1 Day 1

    Close Top of page
    End point title
    Dose-normalized AUCtau [AUCtau (dn) ] After a single dose on Cycle 1 Day 1
    End point description
    AUCtau (dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Analysis population included all treated subjects who had at least 1 of the PK parameters of interest. N=number of subjects evaluable for this endpoint. 99999 signifies data that are not estimable.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, and 10 hr post-dose)
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    3
    3
    3
    7
    3
    21
    16
    2
    4
    Units: (ng*hr/mL)/mg
        geometric mean (geometric coefficient of variation)
    20.4 ± 83
    33.2 ± 87
    20.6 ± 98
    22.0 ± 37
    22.5 ± 81
    24.5 ± 86
    16.3 ± 58
    24.3 ± 99999
    42.7 ± 80
    No statistical analyses for this end point

    Secondary: Dose-normalized AUCtau [AUCtau (dn)] After Multiple Dose on Cycle 1 Day 21

    Close Top of page
    End point title
    Dose-normalized AUCtau [AUCtau (dn)] After Multiple Dose on Cycle 1 Day 21 [61]
    End point description
    AUCtau (dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. 99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3.Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)
    Notes
    [61] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2
    2
    3
    5
    3
    12
    8
    4
    Units: (ng*hr/mL)/mg
        geometric mean (geometric coefficient of variation)
    15.4 ± 99999
    63.0 ± 99999
    19.7 ± 41
    47.4 ± 70
    24.3 ± 59
    42.9 ± 88
    47.9 ± 89
    61.1 ± 30
    No statistical analyses for this end point

    Secondary: Dose-normalized Cmax [Cmax (dn)] After Multiple Dose on Cycle 1 Day 21

    Close Top of page
    End point title
    Dose-normalized Cmax [Cmax (dn)] After Multiple Dose on Cycle 1 Day 21 [62]
    End point description
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. 99999 represents data not estimable (NE) when the number (No.) of subjects analyzed is less than (<) 3.Analysis population included all subjects who had at least 6 days of uninterrupted dosing prior to the Cycle 1 Day 21 PK assessment. The 6-day duration was chosen based on the observed terminal half-life of PF-03084014. N=number of subjects evaluable for this endpoint. Cycle 1 Day 21 PK parameter summaries are presented only for subjects who were considered to be dose compliant.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 21 (pre-dose and 0.5, 1, 2, 4, 10, 24, 48, 96 and 120 hr post-dose)
    Notes
    [62] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No data was available for the 330 mg BID in solid tumor subjects arm
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Number of subjects analysed
    2
    2
    3
    5
    3
    12
    8
    4
    Units: ng/mL/mg
        geometric mean (geometric coefficient of variation)
    3.2 ± 99999
    9.6 ± 99999
    3.9 ± 29
    8.7 ± 44
    3.2 ± 130
    8.3 ± 79
    8.5 ± 76
    12.2 ± 42
    No statistical analyses for this end point

    Secondary: AUCtau in the Fasted State for Solid Tumor Subjects

    Close Top of page
    End point title
    AUCtau in the Fasted State for Solid Tumor Subjects [63]
    End point description
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). Analysis population included solid tumor subjects who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr postdose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    Notes
    [63] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint apples to only solid tumor subjects who participated in food effects study
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    7
    4
    Units: ng*hr/mL
        geometric mean (geometric coefficient of variation)
    2547 ± 101
    9353 ± 100
    No statistical analyses for this end point

    Secondary: AUCtau in the Fed State for Solid Tumor Subjects

    Close Top of page
    End point title
    AUCtau in the Fed State for Solid Tumor Subjects [64]
    End point description
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). Analysis population included solid tumor subjects who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr postdose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    Notes
    [64] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint apples to only solid tumor subjects who participated in food effects study
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    7
    4
    Units: ng*hr/mL
        geometric mean (geometric coefficient of variation)
    3163 ± 83
    5573 ± 39
    No statistical analyses for this end point

    Secondary: Cmax in the Fasted State for Solid Tumor Subjects

    Close Top of page
    End point title
    Cmax in the Fasted State for Solid Tumor Subjects [65]
    End point description
    Cmax was the maximum observed serum concentration. Analysis population included solid tumor subjects who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr postdose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    Notes
    [65] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint apples to only solid tumor subjects who participated in food effects study
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    9
    4
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    795.1 ± 104
    2334 ± 93
    No statistical analyses for this end point

    Secondary: Cmax in the Fed State for Solid Tumor Subjects

    Close Top of page
    End point title
    Cmax in the Fed State for Solid Tumor Subjects [66]
    End point description
    Cmax was the maximum observed serum concentration. Analysis population included solid tumor subjects who were enrolled in the food-effect sub-study, were treated and had evaluable PK data under both fed and fasted states.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr postdose) or Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    Notes
    [66] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint apples to only solid tumor subjects who participated in food effects study
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    9
    4
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    862.3 ± 74
    924.4 ± 40
    No statistical analyses for this end point

    Secondary: AUCtau on Cycle 2 Day 1

    Close Top of page
    End point title
    AUCtau on Cycle 2 Day 1 [67]
    End point description
    AUCtau was area under the serum concentration-time profile from time 0 to tau (dosing interval). Analysis population included all treated subjects who had at least 1 of the PK parameters of interest. N=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    Notes
    [67] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to 150 mg BID and 220 mg BID in solid tumor subjects arms only
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    8
    4
    Units: ng*hr/mL
        geometric mean (geometric coefficient of variation)
    2784 ± 80
    11870 ± 57
    No statistical analyses for this end point

    Secondary: Dose-normalized AUCtau [AUCtau (dn)] on Cycle 2 Day 1

    Close Top of page
    End point title
    Dose-normalized AUCtau [AUCtau (dn)] on Cycle 2 Day 1 [68]
    End point description
    AUCtau(dn) was calculated by area under the serum concentration-time profile from time 0 to tau (dosing interval) (AUCtau) divided by administered dose. Analysis population included all treated subjects who had at least 1 of the PK parameters of interest. N=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    Notes
    [68] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to 150 mg BID and 220 mg BID in solid tumor subjects arms only
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    8
    4
    Units: ng*hr/mL/mg
        geometric mean (geometric coefficient of variation)
    18.6 ± 80
    54.0 ± 57
    No statistical analyses for this end point

    Secondary: Cmax on Cycle 2 Day 1

    Close Top of page
    End point title
    Cmax on Cycle 2 Day 1 [69]
    End point description
    Cmax was the maximum observed serum concentration. Analysis population included all treated subjects who had at least 1 of the PK parameters of interest. N=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    Notes
    [69] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to 150 mg BID and 220 mg BID in solid tumor subjects arms only
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    9
    4
    Units: ng/mL
        geometric mean (geometric coefficient of variation)
    834.6 ± 76
    2640 ± 63
    No statistical analyses for this end point

    Secondary: Dose-normalized Cmax [Cmax (dn)] on Cycle 2 Day 1

    Close Top of page
    End point title
    Dose-normalized Cmax [Cmax (dn)] on Cycle 2 Day 1 [70]
    End point description
    Cmax(dn) was calculated by maximum observed serum concentration (Cmax) divided by administered dose. Analysis population included all treated subjects who had at least 1 of the PK parameters of interest. N=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    Notes
    [70] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to 150 mg BID and 220 mg BID in solid tumor subjects arms only
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    9
    4
    Units: ng/mL/mg
        geometric mean (geometric coefficient of variation)
    5.6 ± 76
    12.0 ± 63
    No statistical analyses for this end point

    Secondary: Tmax on Cycle 2 Day 1

    Close Top of page
    End point title
    Tmax on Cycle 2 Day 1 [71]
    End point description
    Tmax was the time to reach maximum serum concentration (Cmax). Analysis population included all treated subjects who had at least 1 of the PK parameters of interest. N=number of subjects evaluable for this endpoint.
    End point type
    Secondary
    End point timeframe
    Cycle 2 Day 1 (pre-dose and 0.5, 1, 2, 4, 10 and 24 hr post-dose)
    Notes
    [71] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to 150 mg BID and 220 mg BID in solid tumor subjects arms only
    End point values
    PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    9
    4
    Units: hr
        median (full range (min-max))
    2.00 (1.00 to 4.03)
    1.53 (0.98 to 4.00)
    No statistical analyses for this end point

    Post-hoc: Time to Response (TTR) for Solid Tumor Subjects

    Close Top of page
    End point title
    Time to Response (TTR) for Solid Tumor Subjects [72]
    End point description
    TTR was only defined for subjects with an OR. TTR (months) was calculated as (date of first documentation of PR or CR minus date of first dose of study medication plus 1) divided by 30. 99999 signifies data not estimable.
    End point type
    Post-hoc
    End point timeframe
    Baseline, Cycle 2 Day 1, Cycle 3 Day 1 and then Day 1 (+ or -5 days) of every odd cycle or as clinically indicated, up to Cycle 9. Afterwards, assessed on Day 1 (+ or -5 days) every 4 cycles.
    Notes
    [72] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint applies to solid tumor subjects only
    End point values
    PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects
    Number of subjects analysed
    1 [73]
    2
    1 [74]
    1 [75]
    1 [76]
    Units: months
        median (confidence interval 95%)
    11.2 (00000 to 99999)
    19.4 (8.5 to 30.4)
    2.9 (00000 to 99999)
    10.1 (00000 to 99999)
    5.9 (00000 to 99999)
    Notes
    [73] - Data for upper and lower limit of 95% CI were not estimable since only 1 subject was analyzed.
    [74] - Data for upper and lower limit of 95% CI were not estimable since only 1 subject was analyzed.
    [75] - Data for upper and lower limit of 95% CI were not estimable since only 1 subject was analyzed.
    [76] - Data for upper and lower limit of 95% CI were not estimable since only 1 subject was analyzed.
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Two (2) years
    Adverse event reporting additional description
    Same event may appear as AE and SAE, what is presented are distinct events. Event may be categorized as serious in 1 subject and non-serious in another subject or 1 subject may have experienced both serious and non-serious event. The safety analysis set includes all enrolled subjects who receive at least 1 dose of study medication.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    PF-03084014 40 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, patients were to receive PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was to be administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was to be administered BID continuously.

    Reporting group title
    PF-03084014 20 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 was administered orally twice daily (BID), beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, patients were to receive PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was to be administered) followed by 7 days' off-treatment for the purpose of pharmacokinetic (PK) assessments. In Cycle 2 and beyond, PF-03084014 was to be administered BID continuously.

    Reporting group title
    PF-03084014 100 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, patients were to receive PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was to be administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was to be administered BID continuously.

    Reporting group title
    PF-03084014 80 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, patients were to receive PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was to be administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was to be administered BID continuously.

    Reporting group title
    PF-03084014 130 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, patients were to receive PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was to be administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was to be administered BID continuously.

    Reporting group title
    PF-03084014 150 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, patients were to receive PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was to be administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was to be administered BID continuously.

    Reporting group title
    PF-03084014 220 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, patients were to receive PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was to be administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was to be administered BID continuously.

    Reporting group title
    PF-03084014 330 mg BID in Solid Tumor Subjects
    Reporting group description
    PF-03084014 was administered orally BID, beginning on Day 1 of each cycle, for 21 days. In Cycle 1 only, patients were to receive PF-03084014 BID for 21 days (on Cycle 1 Day 21 only the morning dose was to be administered) followed by 7 days' off-treatment for the purpose of PK assessments. In Cycle 2 and beyond, PF-03084014 was to be administered BID continuously.

    Reporting group title
    PF-03084014 in T-ALL/LBL Subjects
    Reporting group description
    PF-03084014 150 mg was administered orally BID to subjects with T-ALL/LBL as single agent for 21 days per cycle continuously (except for Cycle 1). On Cycle 1 Day 21, only the morning dose was administered, followed by a 7-day washout interval.

    Serious adverse events
    PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    4 / 8 (50.00%)
    2 / 4 (50.00%)
    2 / 4 (50.00%)
    8 / 23 (34.78%)
    7 / 16 (43.75%)
    2 / 3 (66.67%)
    4 / 8 (50.00%)
         number of deaths (all causes)
    1
    0
    1
    0
    0
    1
    2
    0
    1
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Arterial injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    GRAM POSITIVE COCCI
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic enzyme abnormal
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutrophil count increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    White blood cell count increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Haemoptysis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infiltration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    2 / 16 (12.50%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 1
    General physical health deterioration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mental status changes
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    2 / 4 (50.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Product issues
    Device dislocation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    2 / 23 (8.70%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abdominal abscess
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fungal infection
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    PF-03084014 40 mg BID in Solid Tumor Subjects PF-03084014 20 mg BID in Solid Tumor Subjects PF-03084014 100 mg BID in Solid Tumor Subjects PF-03084014 80 mg BID in Solid Tumor Subjects PF-03084014 130 mg BID in Solid Tumor Subjects PF-03084014 150 mg BID in Solid Tumor Subjects PF-03084014 220 mg BID in Solid Tumor Subjects PF-03084014 330 mg BID in Solid Tumor Subjects PF-03084014 in T-ALL/LBL Subjects
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    3 / 3 (100.00%)
    7 / 8 (87.50%)
    4 / 4 (100.00%)
    3 / 4 (75.00%)
    23 / 23 (100.00%)
    16 / 16 (100.00%)
    3 / 3 (100.00%)
    8 / 8 (100.00%)
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Flushing
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    2
    1
    0
    0
    Hot flush
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    1 / 23 (4.35%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    1
    1
    0
    0
    Lymphoedema
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Peripheral vascular disorder
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Central nervous system leukaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Lipoma
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Meningioma
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Tumour haemorrhage
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Tumour pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    Immune system disorders
    Contrast media allergy
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Seasonal allergy
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
         occurrences all number
    0
    1
    0
    0
    0
    2
    0
    1
    1
    Chest discomfort
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Chest pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Chills
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Early satiety
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    0
    0
    0
    0
    Facial pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Fatigue
         subjects affected / exposed
    2 / 3 (66.67%)
    2 / 3 (66.67%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    1 / 4 (25.00%)
    12 / 23 (52.17%)
    7 / 16 (43.75%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    3
    2
    2
    4
    1
    14
    11
    2
    0
    General physical health deterioration
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Induration
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    0
    0
    Influenza like illness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    1
    0
    Mucosal dryness
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    2 / 23 (8.70%)
    0 / 16 (0.00%)
    2 / 3 (66.67%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    2
    0
    3
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    1
    0
    1
    0
    1
    1
    0
    0
    Pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    3 / 23 (13.04%)
    2 / 16 (12.50%)
    1 / 3 (33.33%)
    2 / 8 (25.00%)
         occurrences all number
    0
    1
    0
    0
    1
    3
    2
    1
    3
    Psychiatric disorders
    Affective disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Anxiety
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    0
    2
    1
    Confusional state
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    1
    Depressed mood
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    3
    Depression
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    1
    0
    0
    0
    0
    Enuresis
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Hallucination
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Insomnia
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    3 / 23 (13.04%)
    3 / 16 (18.75%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    1
    0
    1
    0
    0
    3
    3
    0
    1
    Obsessive-compulsive disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Reproductive system and breast disorders
    Amenorrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Breast disorder
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Scrotal mass
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Sexual dysfunction
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    1 / 16 (6.25%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    1
    0
    Fall
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    1
    0
    1
    0
    Meniscus injury
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Muscle strain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Procedural pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Rib fracture
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    0
    Road traffic accident
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Skin abrasion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Stoma site pain
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Wound complication
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    1 / 4 (25.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    1
    0
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    0
    1
    4
    2
    0
    1
    0
    0
    5
    Alpha 1 foetoprotein increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    2 / 16 (12.50%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    1
    2
    2
    0
    1
    2
    0
    1
    Bacterial test positive
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    1
    1
    1
    0
    0
    1
    0
    3
    Blood bilirubin increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    2 / 8 (25.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    4
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    1 / 16 (6.25%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    1
    1
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Blood urea increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    C-reactive protein increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    2 / 4 (50.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    2
    0
    0
    0
    0
    0
    Fungal test positive
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    1
    Gamma-glutamyltransferase
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    0
    5
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    5
    Haemoglobin decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    2
    0
    0
    International normalised ratio increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    Platelet count decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Prothrombin time prolonged
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    3
    0
    0
    Transaminases increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    0
    1
    Weight decreased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    0
    0
    1
    0
    White blood cell count increased
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    2
    0
    Sinus tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    1 / 4 (25.00%)
    2 / 4 (50.00%)
    5 / 23 (21.74%)
    5 / 16 (31.25%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    0
    1
    3
    5
    5
    2
    2
    Dysphonia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Dyspnoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    4 / 23 (17.39%)
    2 / 16 (12.50%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    1
    0
    0
    4
    2
    1
    0
    Dyspnoea exertional
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    2 / 16 (12.50%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    1
    0
    0
    0
    1
    2
    0
    1
    Hypoxia
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    8
    Nasal congestion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    1
    0
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    4 / 23 (17.39%)
    1 / 16 (6.25%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    5
    1
    2
    0
    Pleural effusion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    1
    Productive cough
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    1 / 8 (12.50%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    1
    1
    Pulmonary embolism
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    0
    0
    0
    0
    Respiratory tract congestion
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    1
    0
    0
    Rhinitis allergic
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    0
    0
    0
    0
    0
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    1 / 16 (6.25%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    0
    1
    0
    0
    Rhonchi
         subjects affected / exposed
    0 / 3 (0.00%)
    0 / 3 (0.00%)
    1 / 8 (12.50%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    0 / 23 (0.00%)
    0 / 16 (0.00%)
    0 / 3 (0.00%)
    0 / 8 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    0
    0
    0
    0
    Sinus congestion
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
    0 / 4 (0.00%)
    0 / 4 (0.00%)
    1 / 23 (4.35%)
    1 / 16 (6.25%)
    1 / 3 (33.33%)
    0 / 8 (0.00%)
         occurrences all number
    0
    1
    0
    0