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   43857   clinical trials with a EudraCT protocol, of which   7284   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:
    Open-label Study to Assess the Long-term Safety and Efficacy of Momelotinib in Subjects with Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia

    Summary
    EudraCT number
    		 2013-004476-36
    Trial protocol
    		 DE  
    Global end of trial date
    06 Dec 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Jun 2020
    First version publication date
    14 Jun 2020
    Other versions
    Summary report(s)
    		 GS-US-352-1154 Final CSR Synopsis

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GS-US-352-1154
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02124746
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Sierra Oncology, Inc.
    Sponsor organisation address
    46701 Commerce Center Drive, Plymouth, United States,
    Public contact
    Dr. Barbara Klencke, Sierra Oncology, Inc., bklencke@sierraoncology.com
    Scientific contact
    Dr. Barbara Klencke, Sierra Oncology, Inc., bklencke@sierraoncology.com
    Sponsor organisation name
    Gilead Sciences International Ltd.
    Sponsor organisation address
    333 Lakeside Drive, Foster City, United States,
    Public contact
    Clinical Trials Mailbox,, Gilead Sciences International Ltd., clinical.trials@gilead.com
    Scientific contact
    Clinical Trials Mailbox,, Gilead Sciences International Ltd., clinical.trials@gilead.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
    21 Jan 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Dec 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Dec 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this extension study was to determine long-term safety and tolerability of momelotinib (MMB) in 4 cohorts: • Cohort 1: Subjects who received MMB capsules in Study CCL09101E for primary myelofibrosis (PMF), post-polycythemia vera (PV) myelofibrosis (MF), and post essential thrombocythemia (ET) MF without documented progressive disease. • Cohort 2: Subjects who received MMB capsules in Study YM387-II-02 for PMF, post PV/ET MF without documented progressive disease. • Cohort 3: Subjects who received MMB tablets in Study GS-US-354-0101 for PV or ET who completed 24 weeks of treatment and whose disease had not progressed on study. • Cohort 4: Subjects who received MMB tablets in Study GS-US-352-1672 for PMF, post-PV MF, and post-ET MF, who completed 24 weeks of treatment in Study GS-US-352-1672 and responded to treatment while on study. Cohort 3 was discontinued due to limited efficacy of MMB in the treatment of PV and ET in Study GS-US-354-0101.
    Protection of trial subjects
    The protocol, protocol amendments, consent forms, and administrative letters 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 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. This study was conducted in accordance with recognized international scientific and ethical standards, including but not limited to the International Council for Harmonization (ICH) guideline for Good Clinical Practice (GCP) and the original principles embodied in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 May 2014
    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
    Germany: 1
    Country: Number of subjects enrolled
    France: 2
    Country: Number of subjects enrolled
    United States: 68
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Canada: 13
    Worldwide total number of subjects
    87
    EEA total number of subjects
    3
    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)
    40
    From 65 to 84 years
    46
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Benefiting subjects enrolled in select prior MMB studies (parent studies) were included for continued administration of MMB. Cohort 3 (PV/ET; n=13) was closed and subjects were discontinued due to limited efficacy of MMB in the treatment of PV/ET observed in the parent study. Cohort 3 was excluded from safety and efficacy analyses.

    Pre-assignment
    Screening details
    		 Procedures performed at a regular follow-up visit in the subject’s parent MMB study could be used to fulfill screening criteria and to establish any new medical history for this extension study.

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

    Arms
    Arm title
    		 Rollover Safety Analysis Set (RSAS)
    Arm description
    		 The Rollover Safety Analysis Set as defined in the statistical analysis plan included all subjects with MF (ie, Cohorts 1, 2 and 4) who were enrolled in Study GS-US-352-1154. This analysis set was used for demographic and baseline characteristics, study treatment administration and compliance, safety and efficacy analyses. Subjects enrolled in Cohort 3 (non-MF subjects) were excluded in the analysis sets as the cohort was discontinued due to limited efficacy in the parent study. Of note, 19 subjects in Study GS-US-352-1154 were transitioned to a separate extended access study (SRA-MMB-4365) to continue MMB treatment. These 19 subjects include 13 subjects who completed 48 months or more of the allowed MMB therapy on Study GS-US-352-1154 and 6 additional subjects who were transferred into Study SRA-MMB-4365 prior to reaching Month 48 so that GS-US-352-1154 could be terminated by the sponsor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    momelotinib (MMB)
    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 1 [1]
    		Rollover Safety Analysis Set (RSAS)
    Started
    74
    Completed
    15
    Not completed
    59
         Physician decision
    15
         Consent withdrawn by subject
    6
         Disease progression
    13
         Adverse event, non-fatal
    5
         Death
    6
         Non-compliance with study drug
    1
         Study Terminated by Sponsor
    6
         Lack of efficacy
    7
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The study enrolled subjects in 4 cohorts. One of the cohorts, Cohort 3, consisted of 13 patients who received MMB in Study GS-US-354-0101 for the treatment of PV and ET. Per Amendment 3, Cohort 3 was closed, and all enrolled subjects were discontinued from Study GS-US-352-1154 due to limited efficacy of MMB in the treatment of PV and ET in parent study GS-US-354-0101. All analyses were performed excluding this cohort of non-MF subjects.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Rollover Safety Analysis Set (RSAS)
    Reporting group description
    		 The Rollover Safety Analysis Set as defined in the statistical analysis plan included all subjects with MF (ie, Cohorts 1, 2 and 4) who were enrolled in Study GS-US-352-1154. This analysis set was used for demographic and baseline characteristics, study treatment administration and compliance, safety and efficacy analyses. Subjects enrolled in Cohort 3 (non-MF subjects) were excluded in the analysis sets as the cohort was discontinued due to limited efficacy in the parent study. Of note, 19 subjects in Study GS-US-352-1154 were transitioned to a separate extended access study (SRA-MMB-4365) to continue MMB treatment. These 19 subjects include 13 subjects who completed 48 months or more of the allowed MMB therapy on Study GS-US-352-1154 and 6 additional subjects who were transferred into Study SRA-MMB-4365 prior to reaching Month 48 so that GS-US-352-1154 could be terminated by the sponsor.

    Reporting group values
    		 Rollover Safety Analysis Set (RSAS) Total
    Number of subjects
    		 74 74
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 34 34
        From 65-84 years
    		 39 39
        85 years and over
    		 1 1
    Age continuous
    Units: years
        median (full range (min-max))
    		 66.5 (34.0 to 88.0) -
    Gender categorical
    Units: Subjects
        Female
    		 36 36
        Male
    		 38 38
    Transfusion Dependent at Baseline
    Units: Subjects
        Yes
    		 36 36
        No
    		 35 35
        Missing
    		 3 3

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Rollover Safety Analysis Set (RSAS)
    Reporting group description
    		 The Rollover Safety Analysis Set as defined in the statistical analysis plan included all subjects with MF (ie, Cohorts 1, 2 and 4) who were enrolled in Study GS-US-352-1154. This analysis set was used for demographic and baseline characteristics, study treatment administration and compliance, safety and efficacy analyses. Subjects enrolled in Cohort 3 (non-MF subjects) were excluded in the analysis sets as the cohort was discontinued due to limited efficacy in the parent study. Of note, 19 subjects in Study GS-US-352-1154 were transitioned to a separate extended access study (SRA-MMB-4365) to continue MMB treatment. These 19 subjects include 13 subjects who completed 48 months or more of the allowed MMB therapy on Study GS-US-352-1154 and 6 additional subjects who were transferred into Study SRA-MMB-4365 prior to reaching Month 48 so that GS-US-352-1154 could be terminated by the sponsor.

    Primary: Long Term Safety and Tolerability as Measured by the Incidence and Severity of Adverse Events and Clinical Laboratory Abnormalities

    		 Close Top of page
    End point title
    		 Long Term Safety and Tolerability as Measured by the Incidence and Severity of Adverse Events and Clinical Laboratory Abnormalities [1]
    End point description
    Long-term safety and tolerability profile of MMB based on safety data (adverse events and selected hematology and chemistry laboratory parameters) collected after the first dose of MMB in the parent study.
    End point type
    Primary
    End point timeframe
    From the first dose of MMB in the parent study to 30 days following permanent discontinuation of MMB in Study GS-US-352-1154.
    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: Due to the nature of this endpoint, a statistical analysis was not conducted.
    End point values
    		 Rollover Safety Analysis Set (RSAS)
    Number of subjects analysed
    74
    Units: subjects
        Subjects with at least one AE (any grade)
    73
        Subjects with at least one Grade 3 or higher AE
    62
        Subjects with Grade 3 lab toxicity (highest grade)
    36
        Subjects with Grade 4 lab toxicity (highest grade)
    16
    No statistical analyses for this end point

    Secondary: Splenic Response Rate

    		 Close Top of page
    End point title
    		 Splenic Response Rate
    End point description
    The proportion of subjects achieving a spleen response, defined as a reduction of 50% or more in palpable splenomegaly of a spleen that was at least 10 cm below the LCM at baseline, or a spleen that was palpable at > 5 cm and < 10 cm below the LCM at baseline becoming not palpable for at least 56 days, using baseline of the parent study as the reference.
    End point type
    Secondary
    End point timeframe
    From baseline in the parent study until the last spleen assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of MMB.
    End point values
    		 Rollover Safety Analysis Set (RSAS)
    Number of subjects analysed
    63 [2]
    Units: percentage of subjects
    number (not applicable)
        Spleen response rate
    71.4
    Notes
    [2] - There were 63 RSAS subjects with splenomegaly >5 cm at baseline in the parent studies.
    No statistical analyses for this end point

    Secondary: Duration of Splenic Response

    		 Close Top of page
    End point title
    		 Duration of Splenic Response
    End point description
    The interval from the first onset of splenic response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of splenic response. Loss of response was defined as the reduction of splenomegaly by < 50% among responders (with splenomegaly ≥ 10 cm below the LCM at baseline) that lasts ≥ 56 days, or the recurrence of > 0 cm splenomegaly among responders (with splenomegaly > 5 and < 10 cm at baseline) that lasts ≥ 56 days. Duration of splenic response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
    End point type
    Secondary
    End point timeframe
    From baseline in the parent study until the last spleen assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of MMB.
    End point values
    		 Rollover Safety Analysis Set (RSAS)
    Number of subjects analysed
    45 [3]
    Units: days
        median (inter-quartile range (Q1-Q3))
    990.00 (226.00 to 1802.00)
    Notes
    [3] - There were 45 spleen responders.
    No statistical analyses for this end point

    Secondary: Transfusion Independence Response Rate

    		 Close Top of page
    End point title
    		 Transfusion Independence Response Rate
    End point description
    The proportion of transfusion dependent subjects at entry to a parent study who became transfusion-independent for ≥ 12 weeks at any time from the first dose of MMB in the parent study until the end of Study GS-US-352-1154.
    End point type
    Secondary
    End point timeframe
    From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of MMB.
    End point values
    		 Rollover Safety Analysis Set (RSAS)
    Number of subjects analysed
    36 [4]
    Units: percentage of subjects
    number (not applicable)
        Transfusion independence response rate
    77.8
    Notes
    [4] - There were 36 RSAS subjects who were transfusion dependent at baseline in the parent studies.
    No statistical analyses for this end point

    Secondary: Duration of Transfusion Independence Response

    		 Close Top of page
    End point title
    		 Duration of Transfusion Independence Response
    End point description
    The interval from the first onset date of transfusion independence (in the parent study or Study GS-US-352-1154) to the earliest date of loss of response for participants who are transfusion dependent at baseline in the parent study. Loss of TI response was defined as receiving an RBC transfusion after achieving a TI response. Duration of transfusion independence response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
    End point type
    Secondary
    End point timeframe
    From baseline in the parent study until the last assessment date in Study GS-US-352-1154, up to 30 days following permanent discontinuation of MMB.
    End point values
    		 Rollover Safety Analysis Set (RSAS)
    Number of subjects analysed
    28 [5]
    Units: days
        median (inter-quartile range (Q1-Q3))
    193.50 (110.00 to 701.00)
    Notes
    [5] - There were 28 transfusion independence responders.
    No statistical analyses for this end point

    Secondary: Anemia Response Rate

    		 Close Top of page
    End point title
    		 Anemia Response Rate
    End point description
    The proportion of subjects achieving an anemia response, defined as: • Achieving transfusion independence for ≥ 12 weeks, for subjects who were transfusion-dependent at baseline in the parent study, or • Having ≥ 2 g/dL increase in Hgb from baseline for ≥ 12 weeks, for subjects with Hgb < 10 g/dL at baseline in the parent study who were not transfusion-dependent (Cohort 1) or who were transfusion-independent (Cohort 2).
    End point type
    Secondary
    End point timeframe
    From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of MMB.
    End point values
    		 Rollover Safety Analysis Set (RSAS)
    Number of subjects analysed
    52 [6]
    Units: percentage of subjects
    number (not applicable)
        Anemia response rate
    67.3
    Notes
    [6] - There were 52 RSAS subjects who were anemia response-evaluable at baseline in the parent studies.
    No statistical analyses for this end point

    Secondary: Duration of Anemia Response

    		 Close Top of page
    End point title
    		 Duration of Anemia Response
    End point description
    The interval from the first onset of anemia response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of anemia response. Loss of anemia response was defined as having any RBC transfusion after achieving an anemia response. Duration of anemia response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
    End point type
    Secondary
    End point timeframe
    From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of MMB.
    End point values
    		 Rollover Safety Analysis Set (RSAS)
    Number of subjects analysed
    35 [7]
    Units: days
        median (inter-quartile range (Q1-Q3))
    358.00 (114.0 to 954.00)
    Notes
    [7] - There were 35 anemia responders.
    No statistical analyses for this end point

    Secondary: Rate of RBC Transfusion

    		 Close Top of page
    End point title
    		 Rate of RBC Transfusion
    End point description
    The average number of RBC units per subject month during the parent study and/or Study GS-US-352-1154.
    End point type
    Secondary
    End point timeframe
    From the first dose of MMB in the parent study until the last dose of MMB in Study GS-US-352-1154.
    End point values
    		 Rollover Safety Analysis Set (RSAS)
    Number of subjects analysed
    74
    Units: RBC units per month
    median (full range (min-max))
        Rate in Parent Studies
    0.08 (0.0 to 5.4)
        Rate in Study GS-US-352-1154
    0.00 (0.0 to 4.8)
        Rate Since First Dose of MMB in Parent Studies
    0.06 (0.0 to 4.9)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the first dose of MMB in the parent study until 30 days following permanent discontinuation of MMB in Study GS-US-352-1154.
    Adverse event reporting additional description
    Occurrences may be counted multiple times, since within a given subject, individual grade or causality changes may be recorded. In addition, distinct verbatim terms that are coded to a single preferred term are also counted as separate occurrences. Per protocol, disease progression AEs assessed as unrelated to MMB were not captured as serious.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Rollover Safety Analysis Set
    Reporting group description
    		 The Rollover Safety Analysis Set (RSAS) as defined in the SAP included all subjects with MF (ie, Cohorts 1, 2 and 4) who were enrolled in Study GS-US-352-1154. This analysis set was used for demographic and baseline characteristics, study treatment administration and compliance, safety and efficacy analyses. Subjects enrolled in Cohort 3 (non-MF subjects) were excluded in the analysis sets as the cohort was discontinued due to limited efficacy in the parent study.

    Serious adverse events
    		 Rollover Safety Analysis Set
    Total subjects affected by serious adverse events
         subjects affected / exposed
    49 / 74 (66.22%)
         number of deaths (all causes)
    8
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    ADENOCARCINOMA OF COLON
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    MANTLE CELL LYMPHOMA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    NON-HODGKIN'S LYMPHOMA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    OVARIAN CANCER
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    DEEP VEIN THROMBOSIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HYPOTENSION
         subjects affected / exposed
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    THROMBOSIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    CHEST PAIN
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DEATH
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    PAIN
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PYREXIA
         subjects affected / exposed
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    DYSPNOEA
         subjects affected / exposed
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    PULMONARY EMBOLISM
         subjects affected / exposed
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Psychiatric disorders
    DELIRIUM
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Investigations
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    EJECTION FRACTION DECREASED
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    CRANIOCEREBRAL INJURY
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    FALL
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SUBDURAL HAEMATOMA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    TENDON INJURY
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    TIBIA FRACTURE
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    ANGINA PECTORIS
         subjects affected / exposed
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    AORTIC VALVE DISEASE
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ATRIAL FIBRILLATION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ATRIAL FLUTTER
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ATRIOVENTRICULAR BLOCK
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CARDIAC FAILURE
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    CARDIAC FAILURE ACUTE
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CARDIAC FAILURE CONGESTIVE
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences causally related to treatment / all
    1 / 5
         deaths causally related to treatment / all
    0 / 1
    CARDIOMYOPATHY
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MYOCARDIAL INFARCTION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MYOCARDIAL ISCHAEMIA
         subjects affected / exposed
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    PALPITATIONS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SINUS NODE DYSFUNCTION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    VENTRICULAR TACHYCARDIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    CEREBRAL HAEMORRHAGE
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DIZZINESS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    INTRACRANIAL VENOUS SINUS THROMBOSIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    ISCHAEMIC STROKE
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SYNCOPE
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    TRANSIENT GLOBAL AMNESIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    WERNICKE'S ENCEPHALOPATHY
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    FEBRILE NEUTROPENIA
         subjects affected / exposed
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    NEUTROPENIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    THROMBOCYTOPENIA
         subjects affected / exposed
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    6 / 74 (8.11%)
         occurrences causally related to treatment / all
    1 / 6
         deaths causally related to treatment / all
    0 / 0
    ASCITES
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    COLITIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CONSTIPATION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    DIARRHOEA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    GASTROINTESTINAL HAEMORRHAGE
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HAEMATOCHEZIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MOUTH HAEMORRHAGE
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SALIVARY GLAND ENLARGEMENT
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SMALL INTESTINAL OBSTRUCTION
         subjects affected / exposed
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    VARICES OESOPHAGEAL
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    CHOLECYSTITIS CHRONIC
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Skin and subcutaneous tissue disorders
    HYPERHIDROSIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    HAEMATURIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    NEPHROLITHIASIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PROTEINURIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    BACK PAIN
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    BONE PAIN
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    MUSCULAR WEAKNESS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    MYALGIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    APPENDICITIS
         subjects affected / exposed
    2 / 74 (2.70%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    BACTERIAL INFECTION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    BRONCHITIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CELLULITIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    CLOSTRIDIUM DIFFICILE COLITIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    GASTROENTERITIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    GASTROENTERITIS ESCHERICHIA COLI
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    INFECTION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    LOCALISED INFECTION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    LUNG INFECTION
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 1
    PERITONITIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PHARYNGITIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMOCOCCAL SEPSIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMONIA
         subjects affected / exposed
    7 / 74 (9.46%)
         occurrences causally related to treatment / all
    3 / 8
         deaths causally related to treatment / all
    0 / 0
    PNEUMONIA KLEBSIELLA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PNEUMONIA PNEUMOCOCCAL
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    PYELONEPHRITIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    RESPIRATORY SYNCYTIAL VIRUS INFECTION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    SEPSIS
         subjects affected / exposed
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    SINUSITIS BACTERIAL
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    SYSTEMIC MYCOSIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    URINARY TRACT INFECTION
         subjects affected / exposed
    3 / 74 (4.05%)
         occurrences causally related to treatment / all
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    DEHYDRATION
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    HYPOKALAEMIA
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    METABOLIC ACIDOSIS
         subjects affected / exposed
    1 / 74 (1.35%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Rollover Safety Analysis Set
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    73 / 74 (98.65%)
    Vascular disorders
    FLUSHING
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    9
    HAEMATOMA
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    8
    HYPERTENSION
         subjects affected / exposed
    14 / 74 (18.92%)
         occurrences all number
    16
    HYPOTENSION
         subjects affected / exposed
    16 / 74 (21.62%)
         occurrences all number
    19
    Surgical and medical procedures
    TOOTH EXTRACTION
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    6
    General disorders and administration site conditions
    ASTHENIA
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    5
    CHEST PAIN
         subjects affected / exposed
    7 / 74 (9.46%)
         occurrences all number
    7
    CHILLS
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    5
    FATIGUE
         subjects affected / exposed
    35 / 74 (47.30%)
         occurrences all number
    55
    INFLUENZA LIKE ILLNESS
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    5
    OEDEMA PERIPHERAL
         subjects affected / exposed
    19 / 74 (25.68%)
         occurrences all number
    26
    PAIN
         subjects affected / exposed
    6 / 74 (8.11%)
         occurrences all number
    6
    PYREXIA
         subjects affected / exposed
    16 / 74 (21.62%)
         occurrences all number
    22
    Respiratory, thoracic and mediastinal disorders
    COUGH
         subjects affected / exposed
    21 / 74 (28.38%)
         occurrences all number
    33
    DYSPNOEA
         subjects affected / exposed
    29 / 74 (39.19%)
         occurrences all number
    42
    DYSPNOEA EXERTIONAL
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    EPISTAXIS
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    15
    NASAL CONGESTION
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    5
    OROPHARYNGEAL PAIN
         subjects affected / exposed
    7 / 74 (9.46%)
         occurrences all number
    7
    PRODUCTIVE COUGH
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    5
    SINUS CONGESTION
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    Psychiatric disorders
    ANXIETY
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    DEPRESSION
         subjects affected / exposed
    7 / 74 (9.46%)
         occurrences all number
    7
    INSOMNIA
         subjects affected / exposed
    13 / 74 (17.57%)
         occurrences all number
    13
    Investigations
    ACTIVATED PARTIAL THROMBOPLASTIN TIME PROLONGED
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    7
    ALANINE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    19 / 74 (25.68%)
         occurrences all number
    35
    AMYLASE INCREASED
         subjects affected / exposed
    12 / 74 (16.22%)
         occurrences all number
    30
    ASPARTATE AMINOTRANSFERASE INCREASED
         subjects affected / exposed
    11 / 74 (14.86%)
         occurrences all number
    27
    BLOOD ALKALINE PHOSPHATASE INCREASED
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    12
    BLOOD BILIRUBIN INCREASED
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    15
    BLOOD CREATININE INCREASED
         subjects affected / exposed
    17 / 74 (22.97%)
         occurrences all number
    29
    BLOOD URIC ACID INCREASED
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    ELECTROCARDIOGRAM QT PROLONGED
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    8
    GAMMA-GLUTAMYLTRANSFERASE INCREASED
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    7
    INTERNATIONAL NORMALISED RATIO INCREASED
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    8
    LIPASE INCREASED
         subjects affected / exposed
    15 / 74 (20.27%)
         occurrences all number
    21
    LYMPHOCYTE COUNT DECREASED
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    NEUTROPHIL COUNT DECREASED
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    14
    PLATELET COUNT DECREASED
         subjects affected / exposed
    11 / 74 (14.86%)
         occurrences all number
    32
    WEIGHT DECREASED
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    11
    WEIGHT INCREASED
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    WHITE BLOOD CELL COUNT DECREASED
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    22
    Injury, poisoning and procedural complications
    CONTUSION
         subjects affected / exposed
    22 / 74 (29.73%)
         occurrences all number
    32
    FALL
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    10
    FOOT FRACTURE
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    Cardiac disorders
    ATRIAL FIBRILLATION
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    PERICARDIAL EFFUSION
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    SINUS BRADYCARDIA
         subjects affected / exposed
    7 / 74 (9.46%)
         occurrences all number
    10
    Nervous system disorders
    DIZZINESS
         subjects affected / exposed
    28 / 74 (37.84%)
         occurrences all number
    58
    DYSGEUSIA
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    6
    HEADACHE
         subjects affected / exposed
    28 / 74 (37.84%)
         occurrences all number
    40
    HYPOAESTHESIA
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    6
    NEUROPATHY PERIPHERAL
         subjects affected / exposed
    19 / 74 (25.68%)
         occurrences all number
    38
    PARAESTHESIA
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    7
    PERIPHERAL SENSORY NEUROPATHY
         subjects affected / exposed
    31 / 74 (41.89%)
         occurrences all number
    63
    SYNCOPE
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    Blood and lymphatic system disorders
    ANAEMIA
         subjects affected / exposed
    27 / 74 (36.49%)
         occurrences all number
    73
    LEUKOCYTOSIS
         subjects affected / exposed
    7 / 74 (9.46%)
         occurrences all number
    8
    LEUKOPENIA
         subjects affected / exposed
    9 / 74 (12.16%)
         occurrences all number
    22
    NEUTROPENIA
         subjects affected / exposed
    17 / 74 (22.97%)
         occurrences all number
    36
    THROMBOCYTOPENIA
         subjects affected / exposed
    28 / 74 (37.84%)
         occurrences all number
    126
    THROMBOCYTOSIS
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    7
    Ear and labyrinth disorders
    EAR DISCOMFORT
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    Eye disorders
    CATARACT
         subjects affected / exposed
    9 / 74 (12.16%)
         occurrences all number
    10
    DRY EYE
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    8
    LACRIMATION INCREASED
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    VISION BLURRED
         subjects affected / exposed
    7 / 74 (9.46%)
         occurrences all number
    7
    Gastrointestinal disorders
    ABDOMINAL PAIN
         subjects affected / exposed
    23 / 74 (31.08%)
         occurrences all number
    33
    ABDOMINAL PAIN UPPER
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    CONSTIPATION
         subjects affected / exposed
    19 / 74 (25.68%)
         occurrences all number
    23
    DIARRHOEA
         subjects affected / exposed
    41 / 74 (55.41%)
         occurrences all number
    59
    DYSPEPSIA
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    9
    GASTROOESOPHAGEAL REFLUX DISEASE
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    6
    NAUSEA
         subjects affected / exposed
    33 / 74 (44.59%)
         occurrences all number
    65
    VOMITING
         subjects affected / exposed
    21 / 74 (28.38%)
         occurrences all number
    28
    Skin and subcutaneous tissue disorders
    ALOPECIA
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    8
    NIGHT SWEATS
         subjects affected / exposed
    10 / 74 (13.51%)
         occurrences all number
    13
    PETECHIAE
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    8
    PRURITUS
         subjects affected / exposed
    10 / 74 (13.51%)
         occurrences all number
    12
    RASH
         subjects affected / exposed
    12 / 74 (16.22%)
         occurrences all number
    20
    SKIN LESION
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    SKIN ULCER
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    Renal and urinary disorders
    ACUTE KIDNEY INJURY
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    6
    POLLAKIURIA
         subjects affected / exposed
    6 / 74 (8.11%)
         occurrences all number
    6
    PROTEINURIA
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    6
    URINARY RETENTION
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    5
    Musculoskeletal and connective tissue disorders
    ARTHRALGIA
         subjects affected / exposed
    21 / 74 (28.38%)
         occurrences all number
    34
    BACK PAIN
         subjects affected / exposed
    12 / 74 (16.22%)
         occurrences all number
    22
    BONE PAIN
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    8
    MUSCLE SPASMS
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    5
    MUSCULAR WEAKNESS
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    8
    MUSCULOSKELETAL PAIN
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    5
    MYALGIA
         subjects affected / exposed
    6 / 74 (8.11%)
         occurrences all number
    7
    NECK PAIN
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    5
    PAIN IN EXTREMITY
         subjects affected / exposed
    18 / 74 (24.32%)
         occurrences all number
    31
    Infections and infestations
    BRONCHITIS
         subjects affected / exposed
    7 / 74 (9.46%)
         occurrences all number
    7
    HERPES ZOSTER
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    5
    INFLUENZA
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    9
    LUNG INFECTION
         subjects affected / exposed
    6 / 74 (8.11%)
         occurrences all number
    7
    SINUSITIS
         subjects affected / exposed
    14 / 74 (18.92%)
         occurrences all number
    15
    UPPER RESPIRATORY TRACT INFECTION
         subjects affected / exposed
    14 / 74 (18.92%)
         occurrences all number
    21
    URINARY TRACT INFECTION
         subjects affected / exposed
    23 / 74 (31.08%)
         occurrences all number
    40
    Metabolism and nutrition disorders
    DECREASED APPETITE
         subjects affected / exposed
    10 / 74 (13.51%)
         occurrences all number
    11
    DEHYDRATION
         subjects affected / exposed
    5 / 74 (6.76%)
         occurrences all number
    5
    HYPERGLYCAEMIA
         subjects affected / exposed
    8 / 74 (10.81%)
         occurrences all number
    12
    HYPERKALAEMIA
         subjects affected / exposed
    11 / 74 (14.86%)
         occurrences all number
    16
    HYPERURICAEMIA
         subjects affected / exposed
    18 / 74 (24.32%)
         occurrences all number
    25
    HYPOCALCAEMIA
         subjects affected / exposed
    4 / 74 (5.41%)
         occurrences all number
    4
    HYPOKALAEMIA
         subjects affected / exposed
    6 / 74 (8.11%)
         occurrences all number
    6

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Jul 2014
    • Added ophthalmic examinations • Clarified co-administration of CYP3A4 inhibitors/inducers, breast cancer resistance protein substrates, and organic anion transporting polypeptide inhibitors based on new data • Removed thiocyanate testing as supported by data analysis from Study CCL09101
    22 Aug 2014
    • For Cohorts 1 and 2, added an optional twice-daily dosing regimen for subjects who changed to a once-daily dosing regimen after enrolling in this study • Added more thiamine testing time points • Updated safety information
    24 Jul 2015
    • Removed Cohort 3 because the parent Study GS-US-354-0101 was closed due to limited efficacy of MMB in the treatment of PV and ET. All subjects enrolled in Cohort 3 were discontinued from treatment and Study GS-US -352-1154 • Added Cohort 4 – subjects who completed 24 weeks on Study GS-US-352-1672
    06 Nov 2017
    • Extended protocol study visits to allow continued treatment with MMB as long as the extended access program was available, after which time this study would be terminated

    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.
    Cohort 3 was discontinued and excluded from the safety and efficacy analyses. Data for survival analyses (overall, progression-free, and leukemia-free) could not be presented due to the high level of censoring.
    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-Wed Apr 24 10:18:00 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA