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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43976   clinical trials with a EudraCT protocol, of which   7312   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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 3, Randomized Study to Evaluate the Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects with Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis who were Treated with Ruxolitinib

    Summary
    EudraCT number
    2013-005007-13
    Trial protocol
    DE   GB   IT   FR  
    Global end of trial date
    25 Apr 2019

    Results information
    Results version number
    v1(current)
    This version publication date
    09 May 2021
    First version publication date
    09 May 2021
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    GS-US-352-1214
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02101268
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Sierra Oncology, Inc.
    Sponsor organisation address
    46701 Commerce Center Drive, Plymouth, MI, United States, 48170
    Public contact
    Martha Bond, Sierra Oncology, Inc., +1 4165287431, mbond@sierraoncology.com
    Scientific contact
    Martha Bond, Sierra Oncology, Inc., +1 4165287431, mbond@sierraoncology.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 Jun 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Apr 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To determine the efficacy of momelotinib (MMB) versus best available therapy (BAT) in anemic or thrombocytopenic subjects with primary myelofibrosis (PMF), or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/EF MF) who were treated with ruxolitinib as measured by splenic response rate at Week 24 (SRR24).
    Protection of trial subjects
    The protocol, protocol amendments, consent forms, and study subject information sheets were submitted by each investigator to a duly constituted Independent Ethics Committee (IEC) or Institutional Review Board (IRB) for review and approval before study initiation. Protocol amendments and all revisions to the consent form or study subject information sheet after initial IEC/IRB approval were submitted by the investigator to the IEC/IRB for review and approval before implementation in accordance with regulatory requirements. Study GS-US-352-1214 was conducted under a United States (US) Investigational New Drug (IND) application and in accordance with recognized international scientific and ethical standards, including but not limited to the International Council for Harmonisation (ICH) guideline for Good Clinical Practice (GCP) and the original principles embodied in the Declaration of Helsinki. These standards are consistent with the requirements of the US Code of Federal Regulations (CFR) Title 21, Part 312 (21CFR312), and the European Community Directive 2001/20/EC, as well as other local legislation. Investigators (or designee[s]) were responsible for obtaining written informed consent from each individual who participated in this study after adequate explanation of the aims, methods, objectives, and potential hazards of the study and before undertaking any study-related procedures. Subjects were informed that they were completely free to refuse to enter the study or to withdraw from it at any time for any reason.
    Background therapy
    -
    Evidence for comparator
    The control for this study was Best available therapy. Allowable options for BAT included the investigator’s choice of any agent(s) approved for the treatment of MF or are standard of care in the region where the study was being conducted and for which data or guidelines supported the use of that agent in the management of patients with MF. These included but were not limited to chemotherapy (eg, hydroxyurea), anagrelide, a corticosteroid, hematopoietic growth factor, an immunomodulating agent, androgen, or interferon and may include no MF treatment, as well as more than 1 treatment. Best available therapy could have also included no active therapy, where clinically appropriate, beyond standard supportive care measures which were to be provided to subjects in both arms during the active treatment phase of the study. Multiple BAT agents could have been used in combination or sequentially. In contrast, use of other MF therapeutic agents including hematopoietic growth factor support was not allowed during the treatment phase for subjects in the MMB treatment arm. Subjects randomized to BAT were allowed to receive ruxolitinib because of the absence of alternative approved or guideline-recommended therapies following ruxolitinib. This also reflects the lack of a universally-accepted definition of ruxolitinib treatment failure. In practice, ruxolitinib is often continued despite toxicity if side effects are considered manageable with dose reduction(s), or despite suboptimal disease control given the multifaceted nature of the illness where some disease manifestations may be assessed as potentially benefitting from the continuation of ruxolitinib therapy.
    Actual start date of recruitment
    19 Jun 2014
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety, Efficacy
    Long term follow-up duration
    5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 16
    Country: Number of subjects enrolled
    United Kingdom: 10
    Country: Number of subjects enrolled
    France: 23
    Country: Number of subjects enrolled
    Germany: 16
    Country: Number of subjects enrolled
    Italy: 29
    Country: Number of subjects enrolled
    Canada: 10
    Country: Number of subjects enrolled
    United States: 33
    Country: Number of subjects enrolled
    Israel: 19
    Worldwide total number of subjects
    156
    EEA total number of subjects
    84
    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)
    55
    From 65 to 84 years
    101
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Study was designed for subjects with PMF, post-PV MF, or post-ET MF whose prior treatment with ruxolitinib was associated with anemia and/or thrombocytopenia.

    Pre-assignment
    Screening details
    Subjects were required to be treated with ruxolitinib (RUX) for at least 28 days, complicated by hematologic toxicity characterized by a requirement for RBC transfusion while on RUX, OR, a dose adjustment of RUX to < 20 twice daily at start of or during RUX AND the occurrence of Grade 3 or 4 thrombocytopenia, anemia, or hematoma while on RUX.

    Pre-assignment period milestones
    Number of subjects started
    244 [1]
    Number of subjects completed
    156

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Physician decision: 1
    Reason: Number of subjects
    Consent withdrawn by subject: 3
    Reason: Number of subjects
    Adverse event, non-fatal: 2
    Reason: Number of subjects
    Outside of visit window: 10
    Reason: Number of subjects
    Other: 6
    Reason: Number of subjects
    Did not meet eligibility criteria: 66
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Of the 244 subjects that were screened for the study, 88 subjects were screen failed as described in the Subject Non-Completion reasons (primarily due to not meeting eligibility criteria). 156 subjects completed the baseline period and were randomized for the study.
    Period 1
    Period 1 title
    Baseline
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Momelotinib (MMB)
    Arm description
    -
    Arm type
    Experimental

    Investigational medicinal product name
    Momelotinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects self-administered MMB tablets at 100 mg, 150 mg or 200 mg orally once daily.

    Arm title
    Best Available Therapy (BAT)
    Arm description
    -
    Arm type
    No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Number of subjects in period 1
    Momelotinib (MMB) Best Available Therapy (BAT)
    Started
    104
    52
    Completed
    104
    52
    Period 2
    Period 2 title
    Randomized Treatment Phase
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Momelotinib (MMB)
    Arm description
    Momelotinib is a potent, orally-bioavailable small-molecule inhibitor of JAK1, JAK2 and uniquely amongst the development-stage JAK inhibitors, ACVR1. Subjects were randomized on a 2:1 basis to MMB:BAT. The starting dose of MMB for all subjects in the RT phase was 200 mg (or placebo equivalent) in a single tablet. Momelotinib was to be orally self-administered once daily in the morning, and thereafter at approximately the same time each day.
    Arm type
    Experimental

    Investigational medicinal product name
    Momelotinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects self-administered MMB tablets at 100 mg, 150 mg or 200 mg orally once daily.

    Arm title
    Best Available Therapy (BAT)
    Arm description
    Subjects in the BAT treatment arm received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. Regimens for BAT could include but were not limited to chemotherapy (eg, hydroxyurea), anagrelide, a corticosteroid, hematopoietic growth factor, an immunomodulating agent, androgen, or interferon and may include no MF treatment, as well as more than 1 treatment. Subjects were randomized 2:1 to MMB:BAT.
    Arm type
    Comparator

    Investigational medicinal product name
    Best Available Therapy
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    The reference therapy in this study was BAT. Regimens for BAT could include but were not limited to chemotherapy (eg, hydroxyurea), anagrelide, a corticosteroid, hematopoietic growth factor, an immunomodulating agent, androgen, or interferon and may include no MF treatment, as well as more than 1 treatment.

    Number of subjects in period 2
    Momelotinib (MMB) Best Available Therapy (BAT)
    Started
    104
    52
    Completed
    77
    41
    Not completed
    27
    11
         Physician decision
    4
    1
         Consent withdrawn by subject
    8
    4
         Symptomatic Spleen Growth
    -
    1
         Adverse event, non-fatal
    6
    -
         Death
    5
    4
         Disease Progression
    4
    1
    Period 3
    Period 3 title
    Extension Treatment Phase
    Is this the baseline period?
    No
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    MMB to MMB
    Arm description
    Subjects randomized to the MMB group who tolerated and derived clinical benefit from MMB had the option to continue MMB treatment in an ET phase for up to an additional 204 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Momelotinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects self-administered MMB tablets at 100 mg, 150 mg or 200 mg orally once daily.

    Arm title
    BAT to MMB
    Arm description
    After completion of the RT phase, subjects randomized to the BAT treatment arm had the option to receive MMB 200 mg once daily in an ET phase for up to an additional 204 weeks.
    Arm type
    Experimental

    Investigational medicinal product name
    Momelotinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Subjects self-administered MMB tablets at 100 mg, 150 mg or 200 mg orally once daily.

    Number of subjects in period 3 [2]
    MMB to MMB BAT to MMB
    Started
    64
    40
    Completed
    0
    0
    Not completed
    64
    40
         Physician decision
    5
    2
         Consent withdrawn by subject
    3
    2
         Adverse event, non-fatal
    14
    18
         Death
    5
    1
         Transferred to study SRA-MMB-4365
    15
    7
         Disease Progression
    13
    6
         Lack of efficacy
    9
    4
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: All subjects that participated in the Extension Treatment period either discontinued as described in the Subject Non-Completion Reasons or were transferred to the extended access study SRA-MMB-4365.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Momelotinib (MMB)
    Reporting group description
    -

    Reporting group title
    Best Available Therapy (BAT)
    Reporting group description
    -

    Reporting group values
    Momelotinib (MMB) Best Available Therapy (BAT) Total
    Number of subjects
    104 52 156
    Age categorical
    Units: Subjects
        < 65 years
    41 14 55
        >= 65 years
    63 38 101
    Age continuous
    Units: years
        median (full range (min-max))
    67.0 (61.5 to 72.0) 69.5 (64.0 to 75.0) -
    Gender categorical
    Units: Subjects
        Female
    69 24 93
        Male
    35 28 63
    Race
    Units: Subjects
        White
    83 44 127
        Black or African American
    6 0 6
        Native Hawaiian or Other Pacific Islander
    0 0 0
        Asian
    0 0 0
        American Indian or Alaska Native
    0 0 0
        Not Permitted
    15 8 23
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    5 4 9
        Not Hispanic or Latino
    81 40 121
        Not Permitted
    18 8 26
    Transfusion Dependent
    Units: Subjects
        Yes
    58 27 85
        No
    46 25 71
    Total Symptom Score (TSS)
    Units: Subjects
        < 18
    61 28 89
        >= 18
    43 24 67
    Weight
    Units: kg
        median (inter-quartile range (Q1-Q3))
    75.4 (68.0 to 87.0) 74.0 (62.0 to 81.3) -
    Height
    Units: cm
        median (inter-quartile range (Q1-Q3))
    170.0 (164.0 to 177.8) 168.0 (160.0 to 175.0) -
    Body Mass Index
    Units: kg/m^2
        median (inter-quartile range (Q1-Q3))
    25.9 (23.6 to 28.2) 26.1 (23.5 to 29.1) -
    Hemoglobin
    Units: g/dL
        median (inter-quartile range (Q1-Q3))
    9.0 (7.9 to 10.7) 9.2 (8.5 to 10.1) -
    Subject analysis sets

    Subject analysis set title
    Intent-to-Treat Analysis Set
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    For the RT phase, the ITT Analysis Set included all subjects who were randomized in the study. Subjects were grouped within the ITT by the treatment group to which they were randomized. This is the primary analysis set for efficacy analyses and for demographic and baseline characteristics. For the secondary efficacy endpoint of TSS response rate at Week 24, the analysis was performed on subjects in the ITT Analysis Set who had a baseline TSS > 0 or who had a baseline TSS = 0 but a nonzero or missing TSS at Week 24.

    Subject analysis sets values
    Intent-to-Treat Analysis Set
    Number of subjects
    156
    Age categorical
    Units: Subjects
        < 65 years
    55
        >= 65 years
    101
    Age continuous
    Units: years
        median (full range (min-max))
    68.0 (62.0 to 73.5)
    Gender categorical
    Units: Subjects
        Female
    93
        Male
    63
    Race
    Units: Subjects
        White
    127
        Black or African American
    6
        Native Hawaiian or Other Pacific Islander
    0
        Asian
    0
        American Indian or Alaska Native
    0
        Not Permitted
    23
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    9
        Not Hispanic or Latino
    121
        Not Permitted
    26
    Transfusion Dependent
    Units: Subjects
        Yes
    85
        No
    71
    Total Symptom Score (TSS)
    Units: Subjects
        < 18
    89
        >= 18
    67
    Weight
    Units: kg
        median (inter-quartile range (Q1-Q3))
    75.0 (66.0 to 85.7)
    Height
    Units: cm
        median (inter-quartile range (Q1-Q3))
    170.0 (162.5 to 176.0)
    Body Mass Index
    Units: kg/m^2
        median (inter-quartile range (Q1-Q3))
    26.0 (23.6 to 28.6)
    Hemoglobin
    Units: g/dL
        median (inter-quartile range (Q1-Q3))
    9.0 (8.1 to 10.6)

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Momelotinib (MMB)
    Reporting group description
    -

    Reporting group title
    Best Available Therapy (BAT)
    Reporting group description
    -
    Reporting group title
    Momelotinib (MMB)
    Reporting group description
    Momelotinib is a potent, orally-bioavailable small-molecule inhibitor of JAK1, JAK2 and uniquely amongst the development-stage JAK inhibitors, ACVR1. Subjects were randomized on a 2:1 basis to MMB:BAT. The starting dose of MMB for all subjects in the RT phase was 200 mg (or placebo equivalent) in a single tablet. Momelotinib was to be orally self-administered once daily in the morning, and thereafter at approximately the same time each day.

    Reporting group title
    Best Available Therapy (BAT)
    Reporting group description
    Subjects in the BAT treatment arm received treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may have been changed at any time during the study except during the screening period. Regimens for BAT could include but were not limited to chemotherapy (eg, hydroxyurea), anagrelide, a corticosteroid, hematopoietic growth factor, an immunomodulating agent, androgen, or interferon and may include no MF treatment, as well as more than 1 treatment. Subjects were randomized 2:1 to MMB:BAT.
    Reporting group title
    MMB to MMB
    Reporting group description
    Subjects randomized to the MMB group who tolerated and derived clinical benefit from MMB had the option to continue MMB treatment in an ET phase for up to an additional 204 weeks.

    Reporting group title
    BAT to MMB
    Reporting group description
    After completion of the RT phase, subjects randomized to the BAT treatment arm had the option to receive MMB 200 mg once daily in an ET phase for up to an additional 204 weeks.

    Subject analysis set title
    Intent-to-Treat Analysis Set
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    For the RT phase, the ITT Analysis Set included all subjects who were randomized in the study. Subjects were grouped within the ITT by the treatment group to which they were randomized. This is the primary analysis set for efficacy analyses and for demographic and baseline characteristics. For the secondary efficacy endpoint of TSS response rate at Week 24, the analysis was performed on subjects in the ITT Analysis Set who had a baseline TSS > 0 or who had a baseline TSS = 0 but a nonzero or missing TSS at Week 24.

    Primary: Splenic Response Rate at Week 24

    Close Top of page
    End point title
    Splenic Response Rate at Week 24
    End point description
    The primary endpoint of the study, splenic response rate at Week 24, was defined as the proportion of subjects who achieved a spleen volume reduction of ≥ 35% from baseline at the Week 24 assessment as measured by MRI or CT scans. A similar proportion of subjects achieved a response in the MMB group (6.7%, 7 of 104 subjects) as in the BAT group (5.8%, 3 of 52 subjects) in the ITT population. The difference in response rates was not statistically significant (proportion difference by stratified CMH method [95% CI]: 0.01 [−0.09, 0.10]; p = 0.90). Of the 3 responders in the BAT group, 1 subject received 5 mg ruxolitinib twice daily, increased to 10 mg twice daily, and prednisone/prednisolone; 1 subject received 5 mg ruxolitinib twice daily, prednisone/prednisolone, and hydroxyurea; and 1 subject received 20 mg ruxolitinib twice daily.
    End point type
    Primary
    End point timeframe
    Week 24
    End point values
    Momelotinib (MMB) Best Available Therapy (BAT) Intent-to-Treat Analysis Set
    Number of subjects analysed
    104
    52
    156
    Units: Subjects
        Responder
    7
    3
    10
        Non Responder
    97
    49
    146
    Attachments
    Untitled (Filename: t-srr24.pdf)
    Statistical analysis title
    Analysis of Splenic Response Rate
    Statistical analysis description
    The primary endpoint was splenic response rate at Week 24 is defined as the proportion of subjects who achieved a ≥ 35% reduction in spleen volume at Week 24 versus baseline measured by MRI or CT.
    Comparison groups
    Momelotinib (MMB) v Best Available Therapy (BAT)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.9
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Proportion Difference - Stratified CMH
    Point estimate
    0.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.09
         upper limit
    0.1

    Secondary: Total Symptom Score (TSS) Response Rate at Week 24

    Close Top of page
    End point title
    Total Symptom Score (TSS) Response Rate at Week 24
    End point description
    Response rate in TSS from baseline at Week 24, a prespecified secondary endpoint, was defined as the proportion of subjects who achieved a ≥ 50% reduction in TSS from baseline at Week 24 as measured by the modified MPN-SAF TSS v2.0 diary. Response rate in TSS at Week 24 was analyzed for subjects in the ITT who had a baseline TSS > 0 or subjects who had a baseline TSS = 0 but nonzero or missing TSS at Week 24. In the MMB group, 27 (26.2%) of the 103 evaluable patients had a TSS reduction of ≥ 50% from baseline compared to 3 (5.9%) of the 51 evaluable subjects in the BAT group, indicating a 4- to 5 fold greater symptomatic response improvement in subjects who received MMB compared to BAT. The proportion difference by stratified CMH method (95% CI) was 0.20 (0.09, 0.32); this difference was nominally significant (p < 0.001).
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Momelotinib (MMB) Best Available Therapy (BAT) Intent-to-Treat Analysis Set
    Number of subjects analysed
    103
    51
    154
    Units: Subject
        Responder
    27
    3
    30
        Non Responder
    76
    48
    124
    Attachments
    Untitled (Filename: t-tss24.pdf)
    Statistical analysis title
    Analysis of Response Rate in TSS at Week 24
    Statistical analysis description
    Response rate in TSS from baseline to Week 24 is defined as the proportion of subjects who achieved a ≥ 50% reduction from baseline in TSS at Week 24 as measured by the modified MPN SAF TSS v2.0 diary
    Comparison groups
    Momelotinib (MMB) v Best Available Therapy (BAT)
    Number of subjects included in analysis
    154
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    < 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Proportion Difference - Stratified CMH
    Point estimate
    0.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.09
         upper limit
    0.32

    Secondary: Rate of Red Blood Cell Transfusions in the RT

    Close Top of page
    End point title
    Rate of Red Blood Cell Transfusions in the RT
    End point description
    The rate of RBC transfusions in the RT phase was a prespecified secondary endpoint, defined as the average number of RBC units not associated with clinically overt bleeding per subject-month during the RT Phase. For the ITT analysis set, the median (Q1, Q3) rate of RBC transfusion was lower in the MMB group (0.5 [0.0, 2.4] units/month) compared with the BAT group (1.2 [0.0, 2.8] units/month) through Week 24. The median (Q1, Q3) total number of RBC transfusion units through Week 24 was lower in the MMB group (2.0 [0.0, 11.0]) compared with the BAT group (6.0 [0.0, 10.5]).
    End point type
    Secondary
    End point timeframe
    Baseline to Week 24
    End point values
    Momelotinib (MMB) Best Available Therapy (BAT) Intent-to-Treat Analysis Set
    Number of subjects analysed
    104
    52
    156
    Units: units/month
    median (inter-quartile range (Q1-Q3))
        Responder
    0.5 (0.0 to 2.4)
    1.2 (0.0 to 2.8)
    0.8 (0.0 to 2.6)
    Attachments
    Untitled (Filename: t-rbc24.pdf)
    Statistical analysis title
    Analysis of Rate of RBC Transfusion in the RT
    Statistical analysis description
    Rate of RBC transfusion in the RT phase is defined as the average number of RBC units transfused that was not associated with clinically overt bleeding per subject month during the RT phase
    Comparison groups
    Momelotinib (MMB) v Best Available Therapy (BAT)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.38
    Method
    Negative Binomial Model, Adjusted
    Parameter type
    Rate ratio of RBC transfusion
    Point estimate
    0.8
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.49
         upper limit
    1.31

    Secondary: RBC Transfusion Independence Rate at Week 24

    Close Top of page
    End point title
    RBC Transfusion Independence Rate at Week 24
    End point description
    Red blood cell TI at Week 24 is defined as the absence of RBC transfusion and no hemoglobin level < 8 g/dL in the prior 12 weeks, excluding cases associated with clinically overt bleeding. A nominally greater proportion of subjects in the MMB group was TI at Week 24 (43.3%, 45 subjects) compared with the BAT group (21.2%, 11 subjects) despite containing a lower proportion of TI subjects in the MMB group at baseline (MMB: 30.8%; BAT: 36.5%). The difference was nominally significant (p = 0.001). Overall, the proportion of subjects with TI status increased by 12.5% in the MMB group and decreased by 15.3% in the BAT group at Week 24 compared to baseline.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Momelotinib (MMB) Best Available Therapy (BAT) Intent-to-Treat Analysis Set
    Number of subjects analysed
    104
    52
    156
    Units: Subjects
        Responder
    45
    11
    56
        Non-Responder
    59
    41
    100
    Attachments
    Untitled (Filename: t-rbcti24.pdf)
    Statistical analysis title
    Analysis of RBC TI Rate at Week 24
    Statistical analysis description
    Response rate for TI at Week 24 is defined as the proportion of subjects who were TI at Week 24, where TI was defined as absence of RBC transfusion and no hemoglobin level below 8 g/dL in the prior 12 weeks, excluding cases associated with clinically overt bleeding.
    Comparison groups
    Momelotinib (MMB) v Best Available Therapy (BAT)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.001
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Proportion Difference - Stratified CMH
    Point estimate
    0.23
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.09
         upper limit
    0.37

    Secondary: RBC Transfusion Dependence Rate at Week 24

    Close Top of page
    End point title
    RBC Transfusion Dependence Rate at Week 24
    End point description
    Red blood cell TD rate at Week 24 for the ITT population was a prespecified secondary endpoint, and was defined as having had at least 4 units of RBC transfusion or a hemoglobin level below 8 g/dL in the prior 8 weeks ending with Week 24 (excluding cases associated with clinically overt bleeding). Subjects with the last RT phase participation date prior to Day 162 (ie. missing at Week 24) were considered TD at Week 24. A smaller proportion of the MMB group was TD at Week 24 (50.0%, 52 subjects) compared with the BAT group (63.5%, 33 subjects). The difference was not statistically significant.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    Momelotinib (MMB) Best Available Therapy (BAT) Intent-to-Treat Analysis Set
    Number of subjects analysed
    104
    52
    71
    Units: Subjects
        Dependent
    52
    33
    85
        Not-Dependent
    52
    19
    71
    Attachments
    Untitled (Filename: t-rbctd24.pdf)
    Statistical analysis title
    Analysis of RBC TD Rate at Week 24
    Statistical analysis description
    Response rate for TD at Week 24 is defined as the proportion of subjects who were transfusion dependent at Week 24, where TD was defined as at least 4 units of RBC transfusion or a hemoglobin level below 8 g/dL in the prior 8 weeks excluding cases associated with clinically overt bleeding
    Comparison groups
    Momelotinib (MMB) v Best Available Therapy (BAT)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.1
    Method
    Cochran-Mantel-Haenszel
    Parameter type
    Proportion Difference - Stratified CMH
    Point estimate
    -0.13
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -0.29
         upper limit
    0.03

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were recorded that occurred from initiation of investigational product (IP) until 30 days after the last administration of IP regardless of cause or relationship.
    Adverse event reporting additional description
    All adverse events were recorded in the eCRF database. Serious adverse events needed to be reported within 24 hours of investigator being aware. Severity of AEs were graded using the CTCAE, Version 4.03, per AE (episode) the highest severity grade attained should be reported. All AEs were followed up until resolution when possible.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Momelotinib (MMB)
    Reporting group description
    -

    Reporting group title
    Best Available Therapy (BAT)
    Reporting group description
    -

    Reporting group title
    MMB to MMB
    Reporting group description
    -

    Reporting group title
    BAT to MMB
    Reporting group description
    -

    Serious adverse events
    Momelotinib (MMB) Best Available Therapy (BAT) MMB to MMB BAT to MMB
    Total subjects affected by serious adverse events
         subjects affected / exposed
    37 / 104 (35.58%)
    12 / 52 (23.08%)
    33 / 64 (51.56%)
    19 / 40 (47.50%)
         number of deaths (all causes)
    8
    5
    29
    18
         number of deaths resulting from adverse events
    6
    4
    14
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant melanoma
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Metastatic squamous cell carcinoma
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic vascular disorder
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Embolism
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    2 / 104 (1.92%)
    2 / 52 (3.85%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    3 / 40 (7.50%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 2
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Generalised oedema
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Postmenopausal haemorrhage
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory failure
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary congestion
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory distress
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Post lumbar puncture syndrome
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Procedural pain
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    3 / 104 (2.88%)
    1 / 52 (1.92%)
    1 / 64 (1.56%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Left ventricular failure
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Myocardial ischaemia
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Presyncope
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Restless legs syndrome
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 14
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 104 (3.85%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    4 / 40 (10.00%)
         occurrences causally related to treatment / all
    2 / 9
    0 / 0
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Spontaneous haematoma
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenopathy
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Splenic infarction
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    3 / 40 (7.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematoma
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vestibular disorder
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Retinal vein thrombosis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 104 (0.96%)
    1 / 52 (1.92%)
    1 / 64 (1.56%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastric ulcer
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal angiodysplasia
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 104 (0.00%)
    2 / 52 (3.85%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varices oesophageal
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal wall haematoma
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Visceral venous thrombosis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic cirrhosis
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatic failure
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Skin and subcutaneous tissue disorders
    Erythema multiforme
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephritis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Groin pain
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chondrocalcinosis pyrophosphate
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 104 (1.92%)
    1 / 52 (1.92%)
    6 / 64 (9.38%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    3 / 9
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Sepsis
         subjects affected / exposed
    2 / 104 (1.92%)
    2 / 52 (3.85%)
    4 / 64 (6.25%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 1
    Bacterial sepsis
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterobacter bacteraemia
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung Infection
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis bacterial
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia viral
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Soft tissue infection
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    1 / 40 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Tumour lysis syndrome
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetes mellitus
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    2 / 40 (5.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gout
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    0 / 40 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Momelotinib (MMB) Best Available Therapy (BAT) MMB to MMB BAT to MMB
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    99 / 104 (95.19%)
    46 / 52 (88.46%)
    63 / 64 (98.44%)
    40 / 40 (100.00%)
    Vascular disorders
    hypertension
         subjects affected / exposed
    10 / 104 (9.62%)
    2 / 52 (3.85%)
    5 / 64 (7.81%)
    2 / 40 (5.00%)
         occurrences all number
    29
    3
    9
    2
    Hypotension
         subjects affected / exposed
    3 / 104 (2.88%)
    2 / 52 (3.85%)
    2 / 64 (3.13%)
    4 / 40 (10.00%)
         occurrences all number
    6
    2
    2
    5
    Haematoma
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    4 / 40 (10.00%)
         occurrences all number
    0
    0
    2
    4
    General disorders and administration site conditions
    Ascites
         subjects affected / exposed
    4 / 104 (3.85%)
    2 / 52 (3.85%)
    2 / 64 (3.13%)
    2 / 40 (5.00%)
         occurrences all number
    5
    2
    4
    2
    Asthenia
         subjects affected / exposed
    20 / 104 (19.23%)
    11 / 52 (21.15%)
    8 / 64 (12.50%)
    11 / 40 (27.50%)
         occurrences all number
    33
    19
    13
    20
    Fatigue
         subjects affected / exposed
    16 / 104 (15.38%)
    10 / 52 (19.23%)
    7 / 64 (10.94%)
    7 / 40 (17.50%)
         occurrences all number
    18
    14
    7
    9
    Pyrexia
         subjects affected / exposed
    13 / 104 (12.50%)
    4 / 52 (7.69%)
    16 / 64 (25.00%)
    10 / 40 (25.00%)
         occurrences all number
    20
    5
    22
    13
    Oedema peripheral
         subjects affected / exposed
    11 / 104 (10.58%)
    6 / 52 (11.54%)
    10 / 64 (15.63%)
    6 / 40 (15.00%)
         occurrences all number
    15
    6
    13
    6
    Early satiety
         subjects affected / exposed
    3 / 104 (2.88%)
    6 / 52 (11.54%)
    2 / 64 (3.13%)
    1 / 40 (2.50%)
         occurrences all number
    4
    6
    2
    1
    Chills
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    2 / 40 (5.00%)
         occurrences all number
    3
    0
    2
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    18 / 104 (17.31%)
    6 / 52 (11.54%)
    17 / 64 (26.56%)
    8 / 40 (20.00%)
         occurrences all number
    22
    7
    27
    17
    Dyspnoea
         subjects affected / exposed
    12 / 104 (11.54%)
    7 / 52 (13.46%)
    5 / 64 (7.81%)
    6 / 40 (15.00%)
         occurrences all number
    18
    7
    5
    9
    Epistaxis
         subjects affected / exposed
    8 / 104 (7.69%)
    6 / 52 (11.54%)
    2 / 64 (3.13%)
    2 / 40 (5.00%)
         occurrences all number
    9
    9
    2
    3
    Pneumonitis
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    1
    2
    Pulmonary oedema
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    0
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    3 / 104 (2.88%)
    4 / 52 (7.69%)
    4 / 64 (6.25%)
    3 / 40 (7.50%)
         occurrences all number
    3
    4
    4
    3
    Investigations
    Weight decreased
         subjects affected / exposed
    10 / 104 (9.62%)
    3 / 52 (5.77%)
    7 / 64 (10.94%)
    5 / 40 (12.50%)
         occurrences all number
    10
    3
    7
    6
    Blood creatinine increased
         subjects affected / exposed
    6 / 104 (5.77%)
    0 / 52 (0.00%)
    5 / 64 (7.81%)
    1 / 40 (2.50%)
         occurrences all number
    7
    0
    5
    1
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    5 / 104 (4.81%)
    3 / 52 (5.77%)
    2 / 64 (3.13%)
    2 / 40 (5.00%)
         occurrences all number
    6
    3
    2
    2
    Fall
         subjects affected / exposed
    2 / 104 (1.92%)
    2 / 52 (3.85%)
    3 / 64 (4.69%)
    2 / 40 (5.00%)
         occurrences all number
    2
    2
    3
    2
    Procedural pain
         subjects affected / exposed
    0 / 104 (0.00%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    1
    0
    2
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    1 / 104 (0.96%)
    1 / 52 (1.92%)
    1 / 64 (1.56%)
    2 / 40 (5.00%)
         occurrences all number
    1
    1
    1
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    16 / 104 (15.38%)
    4 / 52 (7.69%)
    6 / 64 (9.38%)
    6 / 40 (15.00%)
         occurrences all number
    19
    4
    6
    7
    Headache
         subjects affected / exposed
    16 / 104 (15.38%)
    3 / 52 (5.77%)
    4 / 64 (6.25%)
    6 / 40 (15.00%)
         occurrences all number
    20
    4
    5
    10
    Paraesthesia
         subjects affected / exposed
    8 / 104 (7.69%)
    1 / 52 (1.92%)
    4 / 64 (6.25%)
    3 / 40 (7.50%)
         occurrences all number
    11
    1
    4
    3
    Peripheral sensory neuropathy
         subjects affected / exposed
    7 / 104 (6.73%)
    0 / 52 (0.00%)
    6 / 64 (9.38%)
    7 / 40 (17.50%)
         occurrences all number
    9
    0
    8
    8
    Somnolence
         subjects affected / exposed
    2 / 104 (1.92%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    2
    1
    0
    3
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    18 / 104 (17.31%)
    6 / 52 (11.54%)
    8 / 64 (12.50%)
    11 / 40 (27.50%)
         occurrences all number
    30
    9
    13
    17
    Anaemia
         subjects affected / exposed
    15 / 104 (14.42%)
    10 / 52 (19.23%)
    14 / 64 (21.88%)
    6 / 40 (15.00%)
         occurrences all number
    24
    16
    40
    6
    Neutropenia
         subjects affected / exposed
    7 / 104 (6.73%)
    1 / 52 (1.92%)
    2 / 64 (3.13%)
    3 / 40 (7.50%)
         occurrences all number
    10
    3
    4
    3
    Splenomegaly
         subjects affected / exposed
    2 / 104 (1.92%)
    3 / 52 (5.77%)
    1 / 64 (1.56%)
    1 / 40 (2.50%)
         occurrences all number
    3
    3
    1
    3
    Leukocytosis
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    5 / 64 (7.81%)
    3 / 40 (7.50%)
         occurrences all number
    1
    0
    5
    3
    Eye disorders
    Dry eye
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    3 / 40 (7.50%)
         occurrences all number
    0
    0
    0
    3
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    33 / 104 (31.73%)
    8 / 52 (15.38%)
    19 / 64 (29.69%)
    10 / 40 (25.00%)
         occurrences all number
    42
    16
    26
    13
    Nausea
         subjects affected / exposed
    20 / 104 (19.23%)
    5 / 52 (9.62%)
    8 / 64 (12.50%)
    5 / 40 (12.50%)
         occurrences all number
    25
    6
    10
    6
    Abdominal pain
         subjects affected / exposed
    16 / 104 (15.38%)
    7 / 52 (13.46%)
    7 / 64 (10.94%)
    5 / 40 (12.50%)
         occurrences all number
    22
    9
    14
    5
    Constipation
         subjects affected / exposed
    11 / 104 (10.58%)
    2 / 52 (3.85%)
    5 / 64 (7.81%)
    1 / 40 (2.50%)
         occurrences all number
    15
    2
    7
    1
    Dyspepsia
         subjects affected / exposed
    10 / 104 (9.62%)
    1 / 52 (1.92%)
    2 / 64 (3.13%)
    1 / 40 (2.50%)
         occurrences all number
    10
    1
    2
    1
    Abdominal pain upper
         subjects affected / exposed
    8 / 104 (7.69%)
    1 / 52 (1.92%)
    2 / 64 (3.13%)
    4 / 40 (10.00%)
         occurrences all number
    8
    1
    2
    4
    Vomiting
         subjects affected / exposed
    7 / 104 (6.73%)
    1 / 52 (1.92%)
    5 / 64 (7.81%)
    4 / 40 (10.00%)
         occurrences all number
    7
    1
    7
    4
    Abdominal distension
         subjects affected / exposed
    1 / 104 (0.96%)
    3 / 52 (5.77%)
    3 / 64 (4.69%)
    2 / 40 (5.00%)
         occurrences all number
    1
    4
    3
    2
    Dry mouth
         subjects affected / exposed
    2 / 104 (1.92%)
    1 / 52 (1.92%)
    1 / 64 (1.56%)
    2 / 40 (5.00%)
         occurrences all number
    2
    1
    1
    2
    Melaena
         subjects affected / exposed
    1 / 104 (0.96%)
    1 / 52 (1.92%)
    2 / 64 (3.13%)
    2 / 40 (5.00%)
         occurrences all number
    1
    1
    2
    3
    Dysphagia
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    1
    0
    0
    2
    Abdominal wall haematoma
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    0 / 64 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    0
    2
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    13 / 104 (12.50%)
    4 / 52 (7.69%)
    8 / 64 (12.50%)
    3 / 40 (7.50%)
         occurrences all number
    19
    4
    9
    4
    Night sweats
         subjects affected / exposed
    8 / 104 (7.69%)
    4 / 52 (7.69%)
    3 / 64 (4.69%)
    6 / 40 (15.00%)
         occurrences all number
    10
    4
    5
    7
    Hyperhidrosis
         subjects affected / exposed
    5 / 104 (4.81%)
    5 / 52 (9.62%)
    3 / 64 (4.69%)
    2 / 40 (5.00%)
         occurrences all number
    5
    7
    4
    3
    Alopecia
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    4 / 64 (6.25%)
    1 / 40 (2.50%)
         occurrences all number
    1
    0
    4
    1
    Dry skin
         subjects affected / exposed
    2 / 104 (1.92%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    2 / 40 (5.00%)
         occurrences all number
    2
    0
    1
    2
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    3 / 64 (4.69%)
    3 / 40 (7.50%)
         occurrences all number
    1
    0
    4
    4
    Dysuria
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    2 / 40 (5.00%)
         occurrences all number
    1
    0
    4
    2
    Renal failure
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    2
    2
    Urinary incontinence
         subjects affected / exposed
    0 / 104 (0.00%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    2 / 40 (5.00%)
         occurrences all number
    0
    0
    1
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    10 / 104 (9.62%)
    4 / 52 (7.69%)
    6 / 64 (9.38%)
    1 / 40 (2.50%)
         occurrences all number
    10
    4
    6
    1
    Back pain
         subjects affected / exposed
    5 / 104 (4.81%)
    4 / 52 (7.69%)
    9 / 64 (14.06%)
    3 / 40 (7.50%)
         occurrences all number
    7
    4
    9
    4
    Pain in extremity
         subjects affected / exposed
    5 / 104 (4.81%)
    5 / 52 (9.62%)
    7 / 64 (10.94%)
    1 / 40 (2.50%)
         occurrences all number
    5
    5
    7
    1
    Bone pain
         subjects affected / exposed
    2 / 104 (1.92%)
    6 / 52 (11.54%)
    2 / 64 (3.13%)
    3 / 40 (7.50%)
         occurrences all number
    2
    6
    2
    3
    Muscle spasms
         subjects affected / exposed
    3 / 104 (2.88%)
    1 / 52 (1.92%)
    5 / 64 (7.81%)
    2 / 40 (5.00%)
         occurrences all number
    3
    1
    9
    2
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    11 / 104 (10.58%)
    4 / 52 (7.69%)
    8 / 64 (12.50%)
    8 / 40 (20.00%)
         occurrences all number
    15
    7
    14
    16
    Upper respiratory tract infection
         subjects affected / exposed
    9 / 104 (8.65%)
    3 / 52 (5.77%)
    8 / 64 (12.50%)
    5 / 40 (12.50%)
         occurrences all number
    9
    4
    10
    5
    Oral herpes
         subjects affected / exposed
    7 / 104 (6.73%)
    0 / 52 (0.00%)
    2 / 64 (3.13%)
    1 / 40 (2.50%)
         occurrences all number
    7
    0
    2
    1
    Bronchitis
         subjects affected / exposed
    5 / 104 (4.81%)
    2 / 52 (3.85%)
    6 / 64 (9.38%)
    4 / 40 (10.00%)
         occurrences all number
    5
    3
    6
    4
    Nasopharyngitis
         subjects affected / exposed
    4 / 104 (3.85%)
    2 / 52 (3.85%)
    3 / 64 (4.69%)
    2 / 40 (5.00%)
         occurrences all number
    4
    3
    3
    2
    Pneumonia
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    4 / 64 (6.25%)
    3 / 40 (7.50%)
         occurrences all number
    1
    0
    4
    4
    Oral candidiasis
         subjects affected / exposed
    2 / 104 (1.92%)
    1 / 52 (1.92%)
    0 / 64 (0.00%)
    2 / 40 (5.00%)
         occurrences all number
    2
    1
    0
    2
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    8 / 104 (7.69%)
    1 / 52 (1.92%)
    5 / 64 (7.81%)
    2 / 40 (5.00%)
         occurrences all number
    8
    1
    6
    3
    Decreased appetite
         subjects affected / exposed
    7 / 104 (6.73%)
    2 / 52 (3.85%)
    4 / 64 (6.25%)
    5 / 40 (12.50%)
         occurrences all number
    8
    2
    5
    7
    Vitamin B1 deficiency
         subjects affected / exposed
    7 / 104 (6.73%)
    2 / 52 (3.85%)
    6 / 64 (9.38%)
    1 / 40 (2.50%)
         occurrences all number
    7
    2
    6
    1
    Hyperuricaemia
         subjects affected / exposed
    6 / 104 (5.77%)
    2 / 52 (3.85%)
    4 / 64 (6.25%)
    3 / 40 (7.50%)
         occurrences all number
    7
    2
    5
    3
    Hypokalaemia
         subjects affected / exposed
    4 / 104 (3.85%)
    0 / 52 (0.00%)
    3 / 64 (4.69%)
    4 / 40 (10.00%)
         occurrences all number
    5
    0
    4
    5
    Hypocalcaemia
         subjects affected / exposed
    4 / 104 (3.85%)
    1 / 52 (1.92%)
    3 / 64 (4.69%)
    2 / 40 (5.00%)
         occurrences all number
    4
    1
    9
    2
    Hyponatraemia
         subjects affected / exposed
    4 / 104 (3.85%)
    2 / 52 (3.85%)
    2 / 64 (3.13%)
    3 / 40 (7.50%)
         occurrences all number
    5
    2
    2
    3
    Hypophosphataemia
         subjects affected / exposed
    1 / 104 (0.96%)
    0 / 52 (0.00%)
    1 / 64 (1.56%)
    2 / 40 (5.00%)
         occurrences all number
    1
    0
    1
    3

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references

    http://www.ncbi.nlm.nih.gov/pubmed/29275119
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA