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   43845   clinical trials with a EudraCT protocol, of which   7282   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase 2 Study of TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) After at Least 2 Prior Lines of Chemotherapy

    Summary
    EudraCT number
    		 2016-003716-12
    Trial protocol
    		 GB   ES   DE   IT  
    Global end of trial date
    17 Dec 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    22 Aug 2020
    First version publication date
    22 Aug 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    C34004
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03123393
    WHO universal trial number (UTN)
    		 U1111-1187-6208
    Other trial identifiers
    		 NRES: 17/YH/0181
    Sponsors
    Sponsor organisation name
    Takeda
    Sponsor organisation address
    Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge,MA, United States,
    Public contact
    Medical Director, Takeda, +1 866835-2233, GlobalOncologyMedinfo@takeda.com
    Scientific contact
    Medical Director, Takeda, +1 8778253327, trialdisclosures@takeda.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
    17 Dec 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    17 Dec 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study is to assess the efficacy of TAK-659 measured by the independent radiologic review committee (IRC)-assessed overall response rate (ORR) in participants with relapsed or refractory DLBCL.
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Oct 2017
    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
    France: 14
    Country: Number of subjects enrolled
    United Kingdom: 6
    Country: Number of subjects enrolled
    Italy: 8
    Country: Number of subjects enrolled
    Spain: 6
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    United States: 14
    Worldwide total number of subjects
    49
    EEA total number of subjects
    34
    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)
    23
    From 65 to 84 years
    26
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants took part in the study at 26 investigative sites in France, Great Britain, Italy, Spain, Canada, United States from 10 October 2017 to 17 December 2019. The study was terminated by the sponsor before the initiation of the stage 2 efficacy evaluation.

    Pre-assignment
    Screening details
    		 Participants with a diagnosis of relapsed or refractory diffuse large B-cell lymphoma who had at least 2 prior lines of chemotherapy were enrolled in Cohorts A and B. Cohort A received a single dose and Cohort B received ramp-up doses of TAK-659 in Stage 1 of the study.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort A: TAK-659 100 mg
    Arm description
    		 TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-659
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    TAK-659 tablets

    Arm title
    		 Cohort B: TAK-659 Ramp-up Dosing
    Arm description
    		 TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).
    Arm type
    		 Experimental

    Investigational medicinal product name
    TAK-659
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    TAK-659 tablets

    Number of subjects in period 1
    		Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Started
    24
    25
    Completed
    3
    2
    Not completed
    21
    23
         Consent withdrawn by subject
    2
    1
         Study Terminated by Sponsor
    6
    9
         Reason not Specified
    13
    13

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Cohort A: TAK-659 100 mg
    Reporting group description
    		 TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).

    Reporting group title
    Cohort B: TAK-659 Ramp-up Dosing
    Reporting group description
    		 TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).

    Reporting group values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing Total
    Number of subjects
    		 24 25 49
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 13 10 23
        From 65-84 years
    		 11 15 26
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.2 ( 9.01 ) 64.6 ( 11.37 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 6 14 20
        Male
    		 18 11 29
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 1 0 1
        Asian
    		 0 0 0
        Native Hawaiian or Other Pacific Islander
    		 0 0 0
        Black or African American
    		 0 0 0
        White
    		 21 19 40
        More than one race
    		 0 0 0
        Unknown or Not Reported
    		 2 6 8
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino
    		 1 4 5
        Non-Hispanic and Latino
    		 21 13 34
        Not Reported
    		 2 7 9
        Unknown
    		 0 1 1
    Region of Enrollment
    Units: Subjects
        France
    		 3 11 14
        United Kingdom
    		 3 3 6
        Italy
    		 4 4 8
        Spain
    		 3 3 6
        Canada
    		 1 0 1
        United States
    		 10 4 14
    Height
    Units: cm
        arithmetic mean (standard deviation)
    		 172.8 ( 9.55 ) 167.5 ( 9.52 ) -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    		 92.88 ( 21.132 ) 72.81 ( 18.388 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Cohort A: TAK-659 100 mg
    Reporting group description
    		 TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).

    Reporting group title
    Cohort B: TAK-659 Ramp-up Dosing
    Reporting group description
    		 TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).

    Primary: Stage 2: ORR as Assessed by Independent Radiologic Review Committee (IRRC) Based on Modified 2007 International Working Group (IWG) Criteria

    		 Close Top of page
    End point title
    		 Stage 2: ORR as Assessed by Independent Radiologic Review Committee (IRRC) Based on Modified 2007 International Working Group (IWG) Criteria [1]
    End point description
    ORR was defined as the percentage of participants with complete response (CR), or partial response (PR) as assessed by IRRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
    End point type
    Primary
    End point timeframe
    Up to 12 months
    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: Not Applicable.
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [2]
    0 [3]
    Units: percentage of participants
    Notes
    [2] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [3] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: CR Rate as Assessed by IRC Based on Modified 2007 IWG Criteria

    		 Close Top of page
    End point title
    		 Stage 2: CR Rate as Assessed by IRC Based on Modified 2007 IWG Criteria
    End point description
    CR rate was defined as percentage of participants with complete response as assessed by IRC according to the modified 2007 IWG. CR was defined as disappearance of all evidence of disease.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [4]
    0 [5]
    Units: percentage of participants
    Notes
    [4] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [5] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: ORR as Assessed by IRRC Based on 2014 IWG-Lugano Criteria

    		 Close Top of page
    End point title
    		 Stage 2: ORR as Assessed by IRRC Based on 2014 IWG-Lugano Criteria
    End point description
    ORR was defined as the percentage of participants with CR or PR as assessed by IRRC according to the 2014 Lugano classification, IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [6]
    0 [7]
    Units: percentage of participants
    Notes
    [6] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [7] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: CR Rate as Assessed by IRRC Based on 2014 IWG-Lugano Criteria

    		 Close Top of page
    End point title
    		 Stage 2: CR Rate as Assessed by IRRC Based on 2014 IWG-Lugano Criteria
    End point description
    CR rate was defined as percentage of participants with complete response as assessed by IRC according to the 2014 Lugano classification, IWG criteria. CR was defined as disappearance of all evidence of disease.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [8]
    0 [9]
    Units: percentage of participants
    Notes
    [8] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [9] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: Duration of Response (DOR)

    		 Close Top of page
    End point title
    		 Stage 2: Duration of Response (DOR)
    End point description
    DOR was defined as the time from the date of first documentation of a CR/PR to the date of first documentation of tumor progression or progressive disease (PD) per IRRC assessment according to IWG criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [10]
    0 [11]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    Notes
    [10] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [11] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: Duration of CR

    		 Close Top of page
    End point title
    		 Stage 2: Duration of CR
    End point description
    Duration of CR was defined as the time from the date of first documentation of a CR/PR to the date of first documentation of tumor progression or PD per IRRC assessment according to IWG criteria. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [12]
    0 [13]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    Notes
    [12] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [13] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: ORR as Assessed by IRRC in Participants with Germinal Center B-cell (GCB) DLBCL

    		 Close Top of page
    End point title
    		 Stage 2: ORR as Assessed by IRRC in Participants with Germinal Center B-cell (GCB) DLBCL
    End point description
    ORR was defined as the percentage of participants with CR or PR as assessed by IRRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [14]
    0 [15]
    Units: percentage of participants
    Notes
    [14] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [15] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: ORR as Assessed by IRC in Participants with DLBCL Transformed from Indolent Non-Hodgkin’s Lymphoma (NHL)

    		 Close Top of page
    End point title
    		 Stage 2: ORR as Assessed by IRC in Participants with DLBCL Transformed from Indolent Non-Hodgkin’s Lymphoma (NHL)
    End point description
    ORR was defined as the percentage of participants with CR or PR as assessed by IRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [16]
    0 [17]
    Units: percentage of participants
    Notes
    [16] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [17] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: Progression Free Survival (PFS) as Assessed by IRC

    		 Close Top of page
    End point title
    		 Stage 2: Progression Free Survival (PFS) as Assessed by IRC
    End point description
    PFS was defined as time from start of study treatment to first documentation of PD per IRC assessment or up to death due to any cause, whichever occurs first based on IWG criteria. PD was defined as presence of any new lesion or increase by >=50% of previously involved sites from nadir.
    End point type
    Secondary
    End point timeframe
    Up to 18 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [18]
    0 [19]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    Notes
    [18] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [19] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Stage 2: Overall Survival (OS)
    End point description
    OS was defined as the time from start of study treatment to date of death due to any cause.
    End point type
    Secondary
    End point timeframe
    Up to 24 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [20]
    0 [21]
    Units: months
        median (full range (min-max))
    ( to )
    ( to )
    Notes
    [20] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [21] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 1: ORR as Assessed by IRRC to Select Stage 2 Dose Regimen of TAK-659 from the Lead-in Dose Exploration Phase

    		 Close Top of page
    End point title
    		 Stage 1: ORR as Assessed by IRRC to Select Stage 2 Dose Regimen of TAK-659 from the Lead-in Dose Exploration Phase
    End point description
    ORR was defined as the percentage of participants with CR or PR as assessed by IRC. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
    End point type
    Secondary
    End point timeframe
    Up to 12 months
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [22]
    0 [23]
    Units: percentage of participants
    Notes
    [22] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [23] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Secondary: Stage 2: ORR as Assessed by IRC at 3, 6, and 9 cycles in Participants with DLBCL

    		 Close Top of page
    End point title
    		 Stage 2: ORR as Assessed by IRC at 3, 6, and 9 cycles in Participants with DLBCL
    End point description
    ORR was defined as the percentage of participants with CR or PR as assessed by IRC according to the modified 2007 IWG criteria for malignant lymphoma. CR was defined as disappearance of all evidence of disease. PR was defined as regression of measurable disease and no new sites.
    End point type
    Secondary
    End point timeframe
    At Cycles 3, 6 and 9 (Up to 12 months) (Each cycle of 28 days)
    End point values
    		 Cohort A: TAK-659 100 mg Cohort B: TAK-659 Ramp-up Dosing
    Number of subjects analysed
    0 [24]
    0 [25]
    Units: percentage of participants
    Notes
    [24] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    [25] - Study was terminated before the initiation of Stage 2, data was not collected for this endpoint.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the signing of the informed consent form (ICF) through 28 days after administration of the last dose of study drug or until the start of subsequent anticancer therapy, whichever occurs first (Up to approximately 14 months).
    Adverse event reporting additional description
    At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Cohort B: TAK-659 Ramp-up Dosing
    Reporting group description
    		 TAK-659 60-100 mg tablet, orally, QD, dose based on safety and tolerability during each 28-days cycle (median exposure was 28 days).

    Reporting group title
    Cohort A: TAK-659 100 mg
    Reporting group description
    		 TAK-659 100 mg tablet, orally, once daily (QD), during each 28-days cycle (median exposure was 41 days).

    Serious adverse events
    		 Cohort B: TAK-659 Ramp-up Dosing Cohort A: TAK-659 100 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 25 (52.00%)
    14 / 24 (58.33%)
         number of deaths (all causes)
    3
    3
         number of deaths resulting from adverse events
    1
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Lymphoma
         subjects affected / exposed
    3 / 25 (12.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal adenocarcinoma
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour associated fever
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural fever
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Encephalopathy
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 25 (8.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone marrow failure
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphocytic infiltration
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 25 (8.00%)
    3 / 24 (12.50%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthenia
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 25 (4.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 25 (4.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 25 (4.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asymptomatic bacteriuria
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Candida sepsis
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterovirus infection
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary nocardiosis
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 25 (0.00%)
    1 / 24 (4.17%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 25 (4.00%)
    0 / 24 (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: 5%
    Non-serious adverse events
    		 Cohort B: TAK-659 Ramp-up Dosing Cohort A: TAK-659 100 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    20 / 25 (80.00%)
    24 / 24 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 25 (8.00%)
    1 / 24 (4.17%)
         occurrences all number
    3
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    8 / 25 (32.00%)
    6 / 24 (25.00%)
         occurrences all number
    9
    8
    Oedema peripheral
         subjects affected / exposed
    2 / 25 (8.00%)
    7 / 24 (29.17%)
         occurrences all number
    2
    9
    Asthenia
         subjects affected / exposed
    1 / 25 (4.00%)
    3 / 24 (12.50%)
         occurrences all number
    1
    3
    Oedema
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Pyrexia
         subjects affected / exposed
    10 / 25 (40.00%)
    9 / 24 (37.50%)
         occurrences all number
    12
    9
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    3 / 25 (12.00%)
    9 / 24 (37.50%)
         occurrences all number
    3
    9
    Dyspnoea
         subjects affected / exposed
    3 / 25 (12.00%)
    4 / 24 (16.67%)
         occurrences all number
    3
    4
    Pleural effusion
         subjects affected / exposed
    1 / 25 (4.00%)
    2 / 24 (8.33%)
         occurrences all number
    1
    2
    Oropharyngeal pain
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Sputum discoloured
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    5 / 25 (20.00%)
    9 / 24 (37.50%)
         occurrences all number
    6
    14
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 25 (16.00%)
    7 / 24 (29.17%)
         occurrences all number
    5
    10
    Amylase increased
         subjects affected / exposed
    4 / 25 (16.00%)
    6 / 24 (25.00%)
         occurrences all number
    4
    7
    Blood creatine phosphokinase increased
         subjects affected / exposed
    2 / 25 (8.00%)
    6 / 24 (25.00%)
         occurrences all number
    5
    15
    Lipase increased
         subjects affected / exposed
    3 / 25 (12.00%)
    4 / 24 (16.67%)
         occurrences all number
    4
    6
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    4 / 25 (16.00%)
    1 / 24 (4.17%)
         occurrences all number
    5
    1
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 25 (0.00%)
    4 / 24 (16.67%)
         occurrences all number
    0
    5
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    2 / 25 (8.00%)
    2 / 24 (8.33%)
         occurrences all number
    2
    2
    C-reactive protein increased
         subjects affected / exposed
    2 / 25 (8.00%)
    1 / 24 (4.17%)
         occurrences all number
    2
    2
    Neutrophil count decreased
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    Platelet count decreased
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 25 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    3
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    2 / 25 (8.00%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    2 / 25 (8.00%)
    3 / 24 (12.50%)
         occurrences all number
    2
    3
    Dizziness
         subjects affected / exposed
    0 / 25 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    4
    Neuropathy peripheral
         subjects affected / exposed
    1 / 25 (4.00%)
    2 / 24 (8.33%)
         occurrences all number
    1
    2
    Hypoaesthesia
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    3
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 25 (20.00%)
    7 / 24 (29.17%)
         occurrences all number
    9
    11
    Neutropenia
         subjects affected / exposed
    4 / 25 (16.00%)
    2 / 24 (8.33%)
         occurrences all number
    6
    4
    Thrombocytopenia
         subjects affected / exposed
    1 / 25 (4.00%)
    3 / 24 (12.50%)
         occurrences all number
    1
    3
    Increased tendency to bruise
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Eye disorders
    Periorbital oedema
         subjects affected / exposed
    3 / 25 (12.00%)
    5 / 24 (20.83%)
         occurrences all number
    3
    9
    Vision blurred
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    2 / 25 (8.00%)
    4 / 24 (16.67%)
         occurrences all number
    2
    4
    Abdominal pain
         subjects affected / exposed
    1 / 25 (4.00%)
    4 / 24 (16.67%)
         occurrences all number
    1
    6
    Constipation
         subjects affected / exposed
    1 / 25 (4.00%)
    3 / 24 (12.50%)
         occurrences all number
    1
    3
    Nausea
         subjects affected / exposed
    2 / 25 (8.00%)
    2 / 24 (8.33%)
         occurrences all number
    2
    2
    Dry mouth
         subjects affected / exposed
    2 / 25 (8.00%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    Vomiting
         subjects affected / exposed
    2 / 25 (8.00%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    Abdominal distension
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 25 (4.00%)
    5 / 24 (20.83%)
         occurrences all number
    1
    8
    Pruritus
         subjects affected / exposed
    1 / 25 (4.00%)
    2 / 24 (8.33%)
         occurrences all number
    1
    2
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 25 (4.00%)
    4 / 24 (16.67%)
         occurrences all number
    1
    4
    Arthralgia
         subjects affected / exposed
    0 / 25 (0.00%)
    3 / 24 (12.50%)
         occurrences all number
    0
    3
    Myalgia
         subjects affected / exposed
    0 / 25 (0.00%)
    2 / 24 (8.33%)
         occurrences all number
    0
    2
    Infections and infestations
    Oral candidiasis
         subjects affected / exposed
    4 / 25 (16.00%)
    2 / 24 (8.33%)
         occurrences all number
    4
    2
    Metabolism and nutrition disorders
    Hypophosphataemia
         subjects affected / exposed
    1 / 25 (4.00%)
    7 / 24 (29.17%)
         occurrences all number
    2
    8
    Decreased appetite
         subjects affected / exposed
    2 / 25 (8.00%)
    1 / 24 (4.17%)
         occurrences all number
    2
    1
    Hypokalaemia
         subjects affected / exposed
    2 / 25 (8.00%)
    0 / 24 (0.00%)
         occurrences all number
    2
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Nov 2017
    • The study design was revised to add a dose exploration phase (Stage 1) to select the dosing regimen for use in the efficacy evaluation phase of the study (Stage 2), and statistical methods were revised accordingly. • Clinical experience with TAK-659 was revised to include updated safety and efficacy data from Studies C34001 and C34002, and the rationale for dose and schedule selection was revised with updated safety and efficacy data from Study C34001. • The objectives and endpoints were revised to reflect new 2-phase study design: dose exploration phase, (Stage 1) and efficacy evaluation phase (Stage 2). Secondary objectives and endpoints were revised, as were PK measurements. • The expected numbers of participants and study centers and the expected duration of the study were increased.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    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-Fri Apr 19 08:58:28 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA