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   43865   clinical trials with a EudraCT protocol, of which   7286   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 Two-arm, Phase 1b/2 Study of IPI-145 Administered in Combination with Rituximab or Obinutuzumab in Subjects with Previously Untreated CD20+ Follicular Lymphoma

    Summary
    EudraCT number
    		 2014-005459-13
    Trial protocol
    		 IT   BE   ES   GB  
    Global end of trial date
    06 Jan 2017

    Results information
    Results version number
    		 v2(current)
    This version publication date
    25 Nov 2023
    First version publication date
    06 Jul 2018
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Results contact has changed.
    Summary report(s)
    		 Sponsor Statement
    Transferring letter from Infinity
    Transferring letter from Verastem

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IPI-145-19
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND Number: 112,486
    Sponsors
    Sponsor organisation name
    Secura Bio, Inc.
    Sponsor organisation address
    1995 Village Center Circle, Suite 128, Las Vegas, NV, United States, 89134
    Public contact
    Beth Gregory, PharmD, MBA , Secura Bio, Inc., 1 702-254-0011, bgregory@securabio.com
    Scientific contact
    Beth Gregory, PharmD, MBA , Secura Bio, Inc., 1 702-254-0011, bgregory@securabio.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
    27 Dec 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jan 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Evaluate the safety and assess the clinical activityof IPI-145 in combination with rituximab or obinutuzumab in subjects with previously untreated CD20+ follicular lymphoma (FL)
    Protection of trial subjects
    Prior to screening for enrollment into the clinical trial, all patients were provided detailed information about the investigational product and the trial. During the informed consent process, patients were allowed to ask questions and have a conversation with the study staff providing consent. The informed consent form (ICF) included all elements required by ICH, GCP, and adhered to the IRB/IEC requirements and the ethical principles that have their origin in the Declaration of Helsinki. It was explained to patients during this conversation that they have the right to withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. The ICF was updated when important new information became available, and all patients still receiving treatment in the trial were re-consented on the new information. During the trial, protection of trial subjects took the form of adverse event and concomitant medication monitoring, and disease response monitoring. Adverse events (AEs) were monitored from the time of signing the ICF. The Protocol provided information on what concomitant medication and therapies were either not allowed or should be used with caution. An assessment of these medications and therapies was performed at every clinic visit. Lastly, disease response assessments were performed according to the schedule stipulated in the Protocol. If a study subject progressed, appropriate conversations were had with their study investigator to determine the best course of action for further treatment or management of their disease, outside of the clinical trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    07 May 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 13
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    United States: 19
    Country: Number of subjects enrolled
    Belgium: 9
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Italy: 2
    Worldwide total number of subjects
    55
    EEA total number of subjects
    36
    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)
    36
    From 65 to 84 years
    19
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 The Screening Period Assessments will occur over a period of up to 30 days prior to first dose of study drug (Cycle 1 Day 1).

    Period 1
    Period 1 title
    Treatment period (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Duvelisib (25 mg BID) + Rituximab
    Arm description
    		 Subjects self-administered duvelisib orally continuously twice per day (BID) over 28-day treatment cycles. Rituximab was administered as an intravenous (IV) infusion (375 mg/m ) in four weekly doses in an Induction Period and then a dose was administered every 2 cycles (12 doses) in the Maintenance Period for a total of up to 16 doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Duvelisib
    Investigational medicinal product code
    IPI-145
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Duvelisib will be self-administered BID at a starting dose of 25 mg (or, if determined by DLT assessment, a lower dose of 15 mg) in 28-day cycles beginning on the morning of Cycle 1 Day 1.

    Investigational medicinal product name
    Rituximab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Rituximab will be administered by IV infusion at a dose of 375 mg/m2. A treatment cycle is defined as lasting 28 days.

    Arm title
    		 Duvelisib (25 mg BID) + Obinutuzumab
    Arm description
    		 Subjects self-administered duvelisib orally continuously BID over 28-day treatment cycles. Obinutuzumab was administered as an IV infusion (1000 mg) in four weekly doses in the Induction Period and then a dose was administered every 2 cycles (12 doses) in the Maintenance Period for a total of up to 16 doses.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Duvelisib
    Investigational medicinal product code
    IPI-145
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Duvelisib will be self-administered BID at a starting dose of 25 mg (or, if determined by DLT assessment, a lower dose of 15 mg) in 28-day cycles beginning on the morning of Cycle 1 Day 1.

    Investigational medicinal product name
    Obinutuzumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Obinutuzumab will be administered by IV infusion at a dose of 1000 mg. A treatment cycle is defined as lasting 28 days.

    Number of subjects in period 1
    		Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Started
    28
    27
    Completed
    0
    1
    Not completed
    28
    26
         Consent withdrawn by subject
    1
    -
         Death
    2
    -
         Other
    4
    6
         Termination of the study by the sponsor
    20
    20
         Lost to follow-up
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Duvelisib (25 mg BID) + Rituximab
    Reporting group description
    		 Subjects self-administered duvelisib orally continuously twice per day (BID) over 28-day treatment cycles. Rituximab was administered as an intravenous (IV) infusion (375 mg/m ) in four weekly doses in an Induction Period and then a dose was administered every 2 cycles (12 doses) in the Maintenance Period for a total of up to 16 doses.

    Reporting group title
    Duvelisib (25 mg BID) + Obinutuzumab
    Reporting group description
    		 Subjects self-administered duvelisib orally continuously BID over 28-day treatment cycles. Obinutuzumab was administered as an IV infusion (1000 mg) in four weekly doses in the Induction Period and then a dose was administered every 2 cycles (12 doses) in the Maintenance Period for a total of up to 16 doses.

    Reporting group values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab Total
    Number of subjects
    		 28 27 55
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 20 16 36
        From 65-84 years
    		 8 11 19
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 58.2 (36 to 79) 58.4 (32 to 77) -
    Gender categorical
    Units: Subjects
        Female
    		 10 16 26
        Male
    		 18 11 29

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Duvelisib (25 mg BID) + Rituximab
    Reporting group description
    		 Subjects self-administered duvelisib orally continuously twice per day (BID) over 28-day treatment cycles. Rituximab was administered as an intravenous (IV) infusion (375 mg/m ) in four weekly doses in an Induction Period and then a dose was administered every 2 cycles (12 doses) in the Maintenance Period for a total of up to 16 doses.

    Reporting group title
    Duvelisib (25 mg BID) + Obinutuzumab
    Reporting group description
    		 Subjects self-administered duvelisib orally continuously BID over 28-day treatment cycles. Obinutuzumab was administered as an IV infusion (1000 mg) in four weekly doses in the Induction Period and then a dose was administered every 2 cycles (12 doses) in the Maintenance Period for a total of up to 16 doses.

    Primary: Dose Limiting Toxicities

    		 Close Top of page
    End point title
    		 Dose Limiting Toxicities [1]
    End point description
    The dose limiting toxicity (DLT)-Evaluable analysis set was defined as all subjects in Part 1 of the study who either experienced a DLT during Cycle 1 or completed at least 75% of the prescribed Cycle 1 doses of duvelisib and rituximab or duvelisib and obinutuzumab. This analysis set was used to determine the dose level for Part 2. One DLT occurred in the DO arm: Grade 3 elevated lipase on Day 8 of study treatment. Treatment with duvelisib was interrupted and obinutuzumab was continued.
    End point type
    Primary
    End point timeframe
    All subjects in Part 1 of the study who either experienced a DLT during Cycle 1 or completed at least 75% of the prescribed Cycle 1 doses of duvelisib and rituximab or duvelisib and obinutuzumab.
    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: Data were summarized as descriptive statistics only for this endpoint.
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    6
    6 [2]
    Units: Number of subjects
    0
    1
    Notes
    [2] - 1 DLT in DO arm: Treatment with duvelisib was interrupted and obinutuzumab was continued.
    No statistical analyses for this end point

    Primary: Complete Response (CR)

    		 Close Top of page
    End point title
    		 Complete Response (CR) [3]
    End point description
    CRR was tested against the null (≤ 15%) by a 1-sided exact binomial test at 0.05 level for each arm separately. The estimated CRR along with the 2-sided 95% exact confidence interval was provided. Subjects with missing data for overall response was assumed as not having achieved a CR. In the DR arm, 10 (35.7%) subjects had a best response of Complete Response (CR). In the DO arm, 11 (40.7%) subjects had a best response of Complete Response (CR).
    End point type
    Primary
    End point timeframe
    Throughout the study
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Data were summarized as descriptive statistics only for this endpoint.
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
    10
    11
    No statistical analyses for this end point

    Secondary: Anemia - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Anemia - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    13
    11
        Baseline value 0 / Max end value 1
    6
    11
        Baseline value 1 / Max end value 0
    3
    0
        Baseline value 1 / Max end value 1
    4
    2
        Baseline value 1 / Max end value 2
    1
    1
        Baseline value 2 / Max end value 1
    1
    2
    No statistical analyses for this end point

    Secondary: Hemoglobin increased -Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Hemoglobin increased -Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    28
    27
    No statistical analyses for this end point

    Secondary: Leukocytosis - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Leukocytosis - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    28
    27
    No statistical analyses for this end point

    Secondary: Lymphocyte count decreased - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Lymphocyte count decreased - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    10
    3
        Baseline value 0 / Max end value 1
    5
    3
        Baseline value 0 / Max end value 2
    0
    9
        Baseline value 0 / Max end value 3
    1
    2
        Baseline value 0 / Max end value 4
    0
    1
        Baseline value 1 / Max end value 0
    2
    0
        Baseline value 1 / Max end value 1
    4
    3
        Baseline value 1 / Max end value 2
    2
    1
        Baseline value 1 / Max end value 4
    0
    1
        Baseline value 2 / Max end value 0
    1
    0
        Baseline value 2 / Max end value 2
    2
    2
        Baseline value 2 / Max end value 3
    1
    1
        Baseline value 3 / Max end value 3
    0
    1
    No statistical analyses for this end point

    Secondary: Lymphocyte count increased - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Lymphocyte count increased - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    23
    21
        Baseline value 0 / Max end value 2
    4
    4
        Baseline value 0 / Max end value 3
    0
    1
        Baseline value 2 / Max end value 0
    0
    1
        Baseline value 2 / Max end value 2
    1
    0
    No statistical analyses for this end point

    Secondary: Neutrophil count decreased - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Neutrophil count decreased - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    26
    24
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    5
    3
        Baseline value 0 / Max end value 1
    10
    8
        Baseline value 0 / Max end value 2
    2
    0
        Baseline value 0 / Max end value 3
    1
    2
        Baseline value 0 / Max end value 4
    1
    3
        Baseline value 1 / Max end value 1
    1
    2
        Baseline value 1 / Max end value 2
    2
    1
        Baseline value 1 / Max end value 3
    3
    4
        Baseline value 1 / Max end value 4
    1
    0
        Baseline value 2 / Max end value 3
    0
    1
    No statistical analyses for this end point

    Secondary: Platelet count decreased - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Platelet count decreased - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    21
    13
        Baseline value 0 / Max end value 1
    3
    9
        Baseline value 0 / Max end value 2
    0
    1
        Baseline value 0 / Max end value 3
    1
    0
        Baseline value 1 / Max end value 0
    1
    1
        Baseline value 1 / Max end value 1
    2
    3
    No statistical analyses for this end point

    Secondary: White blood cell decreased - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 White blood cell decreased - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    12
    9
        Baseline value 0 / Max end value 1
    11
    10
        Baseline value 0 / Max end value 2
    1
    3
        Baseline value 1 / Max end value 1
    2
    1
        Baseline value 1 / Max end value 2
    1
    2
        Baseline value 1 / Max end value 3
    0
    1
        Baseline value 2 / Max end value 2
    1
    1
    No statistical analyses for this end point

    Secondary: Creatinine increased - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Creatinine increased - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    27
    26
        Baseline value 0/Max end value 1
    0
    1
        Baseline value 1 / Max end value 0
    1
    0
    No statistical analyses for this end point

    Secondary: Hypercalcemia - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Hypercalcemia - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    28
    27
    No statistical analyses for this end point

    Secondary: Hyperkalemia-Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hyperkalemia-Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    22
    24
        Baseline value 0/Max end value 1
    4
    1
        Baseline value 0 / Max end value 2
    1
    0
        Baseline value 0 / Max end value 4
    0
    1
        Baseline value 1 / Max end value 0
    0
    1
        Baseline value 2 / Max end value 2
    1
    0
    No statistical analyses for this end point

    Secondary: Hypermagnesemia - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hypermagnesemia - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    24
    24
    Units: Number of subjects
        Baseline value 0/Max end value 0
    23
    24
        Baseline value 0 / Max end value 3
    1
    0
    No statistical analyses for this end point

    Secondary: Hypernatremia - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hypernatremia - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    25
    23
        Baseline value 0/Max end value 1
    3
    2
        Baseline value 0 / Max end value 2
    0
    1
        Baseline value 1 / Max end value 0
    0
    1
    No statistical analyses for this end point

    Secondary: Hypoalbuminemia - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hypoalbuminemia - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    26
    Units: Number of subjects
        Baseline value 0/Max end value 0
    23
    16
        Baseline value 0/Max end value 1
    4
    7
        Baseline value 0 / Max end value 2
    0
    1
        Baseline value 1 / Max end value 0
    0
    1
        Baseline value 1 / Max end value 2
    0
    1
        Baseline value 2 / Max end value 2
    1
    0
    No statistical analyses for this end point

    Secondary: Hypocalcemia - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hypocalcemia - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    20
    10
        Baseline value 0 / Max end value 1
    5
    13
        Baseline value 1 / Max end value 0
    0
    1
        Baseline value 1 / Max end value 1
    3
    3
    No statistical analyses for this end point

    Secondary: Hypoglycemia - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hypoglycemia - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    27
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    21
    16
        Baseline value 0 / Max end value 1
    4
    9
        Baseline value 1 / Max end value 0
    0
    1
        Baseline value 1 / Max end value 1
    2
    1
    No statistical analyses for this end point

    Secondary: Hypokalemia - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hypokalemia - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    25
    21
        Baseline value 0 / Max end value 1
    3
    4
        Baseline value 0 / Max end value 3
    0
    2
    No statistical analyses for this end point

    Secondary: Hypomagnesemia- Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hypomagnesemia- Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    24
    24
    Units: Number of subjects
        Baseline value 0/Max end value 0
    15
    10
        Baseline value 0 / Max end value 1
    5
    8
        Baseline value 0 / Max end value 3
    0
    1
        Baseline value 1 / Max end value 1
    4
    5
    No statistical analyses for this end point

    Secondary: Hyponatremia - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hyponatremia - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0/Max end value 0
    19
    23
        Baseline value 0/Max end value 1
    9
    3
        Baseline value 1/ Max end value 1
    0
    1
    No statistical analyses for this end point

    Secondary: Hypophosphatemia - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Hypophosphatemia - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    24
    25
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    10
    5
        Baseline value 0 / Max end value 1
    10
    7
        Baseline value 0 / Max end value 2
    1
    4
        Baseline value 0 / Max end value 3
    0
    2
        Baseline value 1 / Max end value 1
    1
    5
        Baseline value 1 / Max end value 2
    2
    1
        Baseline value 2 / Max end value 2
    0
    1
    No statistical analyses for this end point

    Secondary: Lipase increased - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Lipase increased - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    23
    20
    Units: Number of subjects
        Baseline value 0/Max end value 0
    17
    16
        Baseline value 0 / Max end value 1
    4
    1
        Baseline value 0 / Max end value 3
    2
    1
        Baseline value 0 / Max end value 4
    0
    1
        Baseline value 1 / Max end value 2
    0
    1
    No statistical analyses for this end point

    Secondary: Serum amylase increased - Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Serum amylase increased - Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    22
    23
    Units: Number of subjects
        Baseline value 0/Max end value 0
    21
    21
        Baseline value 0 / Max end value 1
    1
    1
        Baseline value 0 / Max end value 3
    0
    1
    No statistical analyses for this end point

    Secondary: Alanine aminotransferase increased- Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Alanine aminotransferase increased- Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    0
    5
        Baseline value 0 / Max end value 1
    12
    9
        Baseline value 0 / Max end value 2
    2
    4
        Baseline value 0 / Max end value 3
    6
    4
        Baseline value 0 / Max end value 4
    2
    3
        Baseline value 1 / Max end value 0
    1
    0
        Baseline value 1 / Max end value 1
    2
    0
        Baseline value 1 / Max end value 3
    3
    2
    No statistical analyses for this end point

    Secondary: Alkaline phosphatase increased- Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Alkaline phosphatase increased- Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    18
    21
        Baseline value 0 / Max end value 1
    5
    3
        Baseline value 0 / Max end value 2
    0
    1
        Baseline value 0 / Max end value 3
    0
    1
        Baseline value 1 / Max end value 0
    3
    0
        Baseline value 1 / Max end value 1
    2
    1
    No statistical analyses for this end point

    Secondary: Aspartate aminotransferase increased- Maximum post -Baseline grade

    		 Close Top of page
    End point title
    		 Aspartate aminotransferase increased- Maximum post -Baseline grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    26
    24
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    4
    7
        Baseline value 0 / Max end value 1
    9
    8
        Baseline value 0 / Max end value 2
    4
    3
        Baseline value 0 / Max end value 3
    2
    5
        Baseline value 0 / Max end value 4
    1
    0
        Baseline value 1 / Max end value 0
    3
    0
        Baseline value 1 / Max end value 1
    3
    0
        Baseline value 1 / Max end value 3
    0
    1
    No statistical analyses for this end point

    Secondary: Blood bilirubin increased - Maximum Post-Baseline Grade

    		 Close Top of page
    End point title
    		 Blood bilirubin increased - Maximum Post-Baseline Grade
    End point description
    Completed when result different from 0 for at least one arm
    End point type
    Secondary
    End point timeframe
    Throughout the study
    End point values
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Number of subjects analysed
    28
    27
    Units: Number of subjects
        Baseline value 0 / Max end value 0
    20
    18
        Baseline value 0 / Max end value 1
    6
    6
        Baseline value 0 / Max end value 2
    1
    1
        Baseline value 1 / Max end value 0
    0
    1
        Baseline value 1 / Max end value 1
    1
    0
        Baseline value 2 / Max end value 3
    0
    1
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    For all subjects (including screen-failures), monitoring of AEs will be performed from the signing of the ICF through 30 days after the last dose or until the subject is deemed a study failure.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Duvelisib (25 mg BID) + Rituximab
    Reporting group description
    		 -

    Reporting group title
    Duvelisib (25 mg BID) + Obinutuzumab
    Reporting group description
    		 -

    Serious adverse events
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    10 / 28 (35.71%)
    16 / 27 (59.26%)
         number of deaths (all causes)
    2
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lymphoma
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Embolism
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 28 (7.14%)
    4 / 27 (14.81%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 27 (7.41%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Syncope
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    4 / 28 (14.29%)
    2 / 27 (7.41%)
         occurrences causally related to treatment / all
    4 / 4
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Odynophagia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatotoxicity
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash papular
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash generalised
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea infectious
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella infection
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii infection
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia cytomegaloviral
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Pneumonia pneumococcal
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Duvelisib (25 mg BID) + Rituximab Duvelisib (25 mg BID) + Obinutuzumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    27 / 28 (96.43%)
    26 / 27 (96.30%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Lymphoma
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Hypotension
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Orthostatic hypotension
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 27 (3.70%)
         occurrences all number
    2
    1
    Embolism
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 27 (0.00%)
         occurrences all number
    3
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    6 / 28 (21.43%)
    10 / 27 (37.04%)
         occurrences all number
    6
    10
    Fatigue
         subjects affected / exposed
    9 / 28 (32.14%)
    8 / 27 (29.63%)
         occurrences all number
    9
    8
    Asthenia
         subjects affected / exposed
    5 / 28 (17.86%)
    4 / 27 (14.81%)
         occurrences all number
    5
    4
    Malaise
         subjects affected / exposed
    1 / 28 (3.57%)
    4 / 27 (14.81%)
         occurrences all number
    1
    4
    Mucosal inflammation
         subjects affected / exposed
    3 / 28 (10.71%)
    2 / 27 (7.41%)
         occurrences all number
    3
    2
    Chills
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 27 (3.70%)
         occurrences all number
    2
    1
    Discomfort
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Oedema peripheral
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Peripheral swelling
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Systematic inflammatory response syndrome
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Chest discomfort
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Localised oedema
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Pain
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 27 (7.41%)
         occurrences all number
    0
    2
    Hypersensitivity
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Breast discomfort
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Erectile dysfunction
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Oedema genital
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Penile erythema
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    7 / 28 (25.00%)
    6 / 27 (22.22%)
         occurrences all number
    7
    6
    Oropharyngeal pain
         subjects affected / exposed
    2 / 28 (7.14%)
    4 / 27 (14.81%)
         occurrences all number
    2
    4
    Dyspnoea
         subjects affected / exposed
    4 / 28 (14.29%)
    3 / 27 (11.11%)
         occurrences all number
    4
    3
    Pneumonitis
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences all number
    1
    2
    Rhinorrhoea
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 27 (7.41%)
         occurrences all number
    0
    2
    Dyspnoea exertional
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Nasal congestion
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Paranasal sinus discomfort
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Productive cough
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 27 (3.70%)
         occurrences all number
    2
    1
    Sinus congestion
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Throat irritation
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Wheezing
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    5 / 28 (17.86%)
    3 / 27 (11.11%)
         occurrences all number
    5
    3
    Depression
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences all number
    1
    2
    Insomnia
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 27 (3.70%)
         occurrences all number
    2
    1
    Libido decreased
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    9 / 28 (32.14%)
    14 / 27 (51.85%)
         occurrences all number
    9
    14
    Aspartate aminotransferase increased
         subjects affected / exposed
    8 / 28 (28.57%)
    13 / 27 (48.15%)
         occurrences all number
    8
    13
    Amylase increased
         subjects affected / exposed
    3 / 28 (10.71%)
    3 / 27 (11.11%)
         occurrences all number
    3
    3
    Lipase increased
         subjects affected / exposed
    3 / 28 (10.71%)
    3 / 27 (11.11%)
         occurrences all number
    3
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Blood magnesium decreased
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Eosinophil count increased
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Liver function test abnormal
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Transaminases increased
         subjects affected / exposed
    3 / 28 (10.71%)
    1 / 27 (3.70%)
         occurrences all number
    3
    1
    Weight decreased
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Weight increased
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    1 / 28 (3.57%)
    4 / 27 (14.81%)
         occurrences all number
    1
    4
    Excoriation
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Skin abrasion
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Procedural pain
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Tongue injury
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Wound
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Sinus tachycardia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    1 / 28 (3.57%)
    4 / 27 (14.81%)
         occurrences all number
    1
    4
    Headache
         subjects affected / exposed
    4 / 28 (14.29%)
    4 / 27 (14.81%)
         occurrences all number
    4
    4
    Dizziness
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences all number
    1
    2
    Paraesthesia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Sedation
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Hemiparesis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Syncope
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Tremor
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Dysaesthesia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Polyneuropathy
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    4 / 28 (14.29%)
    5 / 27 (18.52%)
         occurrences all number
    4
    5
    Anaemia
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 27 (3.70%)
         occurrences all number
    2
    1
    Febrile neutropenia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Leukocytosis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Thrombocytopenia
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 27 (3.70%)
         occurrences all number
    2
    1
    Leukopenia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 27 (7.41%)
         occurrences all number
    0
    2
    Ear pain
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Ear pruritus
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Eye disorders
    Eye pain
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Eyelid oedema
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Periorbital oedema
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Vision blurred
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Visual acuity reduced
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    7 / 28 (25.00%)
    12 / 27 (44.44%)
         occurrences all number
    7
    12
    Diarrhoea
         subjects affected / exposed
    16 / 28 (57.14%)
    11 / 27 (40.74%)
         occurrences all number
    16
    11
    Abdominal pain
         subjects affected / exposed
    5 / 28 (17.86%)
    8 / 27 (29.63%)
         occurrences all number
    5
    8
    Vomiting
         subjects affected / exposed
    4 / 28 (14.29%)
    8 / 27 (29.63%)
         occurrences all number
    4
    8
    Abdominal pain upper
         subjects affected / exposed
    2 / 28 (7.14%)
    5 / 27 (18.52%)
         occurrences all number
    2
    5
    Constipation
         subjects affected / exposed
    5 / 28 (17.86%)
    4 / 27 (14.81%)
         occurrences all number
    5
    4
    Stomatitis
         subjects affected / exposed
    1 / 28 (3.57%)
    4 / 27 (14.81%)
         occurrences all number
    1
    4
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 28 (10.71%)
    3 / 27 (11.11%)
         occurrences all number
    3
    3
    Colitis
         subjects affected / exposed
    2 / 28 (7.14%)
    2 / 27 (7.41%)
         occurrences all number
    2
    2
    Dyspepsia
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 27 (7.41%)
         occurrences all number
    0
    2
    Odynophagia
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences all number
    1
    2
    Toothache
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 27 (7.41%)
         occurrences all number
    0
    2
    Abdominal discomfort
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Diverticulum
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Dry mouth
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Functional gastrointestinal disorder
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Gastrointestinal hypermotility
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Gingival bleeding
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Oesophagitis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Oral mucosal erythema
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Proctitis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Abdominal pain lower
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Oral pain
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Proctalgia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Hepatobiliary disorders
    Cholestasis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Hepatotoxicity
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Hepatitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    8 / 28 (28.57%)
    8 / 27 (29.63%)
         occurrences all number
    8
    8
    Dry skin
         subjects affected / exposed
    2 / 28 (7.14%)
    3 / 27 (11.11%)
         occurrences all number
    2
    3
    Alopecia
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences all number
    1
    2
    Rash erythematous
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences all number
    1
    2
    Eczema asteatotic
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Erythema
         subjects affected / exposed
    2 / 28 (7.14%)
    1 / 27 (3.70%)
         occurrences all number
    2
    1
    Hyperhidrosis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Night sweats
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Pigmentation disorder
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    3 / 28 (10.71%)
    1 / 27 (3.70%)
         occurrences all number
    3
    1
    Psoriasis
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Purpura
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Rash maculo-papular
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Rash papular
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Skin exfoliation
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Dermatitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Eczema
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Erythema multiforme
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Exfoliative rash
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Hand dermatitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Rash generalised
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 27 (0.00%)
         occurrences all number
    2
    0
    Skin hypopigmentation
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Skin lesion
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Dysuria
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Renal failure
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Pollakiuria
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 27 (0.00%)
         occurrences all number
    2
    0
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    6 / 28 (21.43%)
    3 / 27 (11.11%)
         occurrences all number
    6
    3
    Arthralgia
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences all number
    1
    2
    Muscle spasms
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 27 (7.41%)
         occurrences all number
    0
    2
    Arthritis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Musculoskeletal pain
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Pain in extremity
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Limb discomfort
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Muscular weakness
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 27 (0.00%)
         occurrences all number
    2
    0
    Musculoskeletal discomfort
         subjects affected / exposed
    2 / 28 (7.14%)
    0 / 27 (0.00%)
         occurrences all number
    2
    0
    Myalgia
         subjects affected / exposed
    3 / 28 (10.71%)
    0 / 27 (0.00%)
         occurrences all number
    3
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    1 / 28 (3.57%)
    6 / 27 (22.22%)
         occurrences all number
    1
    6
    Conjunctivitis
         subjects affected / exposed
    1 / 28 (3.57%)
    4 / 27 (14.81%)
         occurrences all number
    1
    4
    Sinusitis
         subjects affected / exposed
    1 / 28 (3.57%)
    2 / 27 (7.41%)
         occurrences all number
    1
    2
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 28 (7.14%)
    2 / 27 (7.41%)
         occurrences all number
    2
    2
    Angular cheilitis
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Bacterial diarrhoea
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Bronchitis
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Candida infections
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Cystitis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Dermatitis infected
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Diarrhoea infectious
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Folliculitis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Genital herpes simplex
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Herpes virus infection
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Herpes zoster
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Klebsiella infection
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Labyrinthitis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Oral herpes
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Otitis media
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Pyelonephritis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Respiratory tract infection
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Sepsis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Septic shock
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Tinea infection
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 28 (3.57%)
    1 / 27 (3.70%)
         occurrences all number
    1
    1
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Vulvovaginal candidiasis
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Anal abscess
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Campylobacter gastroenteritis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Corona virus infection
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Cytomegalovirus infection
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Hordeolum
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Laryngitis
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Lung infection
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Pneumocystis jirovecii infection
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Pneumocystis jirovecii pneumonia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Pneumonia cytomegaloviral
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Pneumonia pneumococcal
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Staphylococcal infection
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Tinea cruris
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 28 (3.57%)
    6 / 27 (22.22%)
         occurrences all number
    1
    6
    Hypokalaemia
         subjects affected / exposed
    1 / 28 (3.57%)
    3 / 27 (11.11%)
         occurrences all number
    1
    3
    Hypomagnesaemia
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 27 (7.41%)
         occurrences all number
    0
    2
    Hypophosphataemia
         subjects affected / exposed
    0 / 28 (0.00%)
    2 / 27 (7.41%)
         occurrences all number
    0
    2
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 28 (0.00%)
    1 / 27 (3.70%)
         occurrences all number
    0
    1
    Gout
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 28 (3.57%)
    0 / 27 (0.00%)
         occurrences all number
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Feb 2015
    Amendment 1, Global
    22 Oct 2015
    Amendment 2, Global
    19 Sep 2016
    Amendment 3, Global. Amendment 3 was not submitted in the EU but was submitted in US but never implemented. No subjects were enrolled under Amendment 3.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    16 Jun 2016
    On the 16th June an Administrative Letter requesting an enrollment hold in Europe until Amendment 3 was approved was issued to all EU investigators.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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-Sat Apr 27 08:46:23 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA