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    Clinical Trial Results:
    An Open-Label, Dose-Finding Study of Vedolizumab IV for Treatment of Steroid-Refractory Acute Intestinal Graft-Versus-Host Disease (GvHD) in Patients who Have Undergone Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT)

    Summary
    EudraCT number
    2016-002985-30
    Trial protocol
    SE   FR   BE  
    Global end of trial date
    09 May 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    22 May 2019
    First version publication date
    22 May 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    Vedolizumab-2004
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02993783
    WHO universal trial number (UTN)
    U1111-1185-6832
    Sponsors
    Sponsor organisation name
    Millennium Pharmaceuticals, Inc.
    Sponsor organisation address
    40 Landsdowne Street, Cambridge, MA, United States, 02139
    Public contact
    Medical Director, Takeda, +1 8778253327, clinicaltrialregistry@tpna.com
    Scientific contact
    Medical Director, Takeda, +1 8778253327, clinicaltrialregistry@tpna.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
    09 May 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 May 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this trial was to describe the initial activity, tolerability, and safety and to identify a recommended dose and regimen of vedolizumab IV administered for treatment of steroid-refractory acute intestinal GvHD in participants who have undergone allo-HSCT.
    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
    28 Apr 2017
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    6 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Norway: 1
    Country: Number of subjects enrolled
    United States: 8
    Worldwide total number of subjects
    17
    EEA total number of subjects
    9
    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)
    13
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Participants took part in the study at 11 investigative sites in the United States, France, Belgium and Norway from 28 April 2017 to 09 May 2018.

    Pre-assignment
    Screening details
    Participants with steroid-refractory acute intestinal graft-versus-host disease (GvHD) who had undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT) were enrolled to receive 300 mg or 600 mg vedolizumab.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Vedolizumab 300 mg
    Arm description
    Vedolizumab 300 mg, intravenous (IV) infusion, once on Days 1, 15, 43, 71 and 99.
    Arm type
    Experimental

    Investigational medicinal product name
    Vedolizumab IV
    Investigational medicinal product code
    MLN0002
    Other name
    Entyvio™
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vedolizumab 300 mg, infusion, intravenously once on Days 1, 15, 43, 71 and 99

    Arm title
    Vedolizumab 600 mg
    Arm description
    Vedolizumab 600 mg, IV infusion, once on Days 1, 15, 43, 71 and 99.
    Arm type
    Experimental

    Investigational medicinal product name
    Vedolizumab IV
    Investigational medicinal product code
    MLN0002
    Other name
    Entyvio™
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Vedolizumab 600 mg, infusion, intravenously once on Days 1, 15, 43, 71 and 99

    Number of subjects in period 1
    Vedolizumab 300 mg Vedolizumab 600 mg
    Started
    8
    9
    Completed
    2
    0
    Not completed
    6
    9
         Reason not Specified
    6
    9

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Vedolizumab 300 mg
    Reporting group description
    Vedolizumab 300 mg, intravenous (IV) infusion, once on Days 1, 15, 43, 71 and 99.

    Reporting group title
    Vedolizumab 600 mg
    Reporting group description
    Vedolizumab 600 mg, IV infusion, once on Days 1, 15, 43, 71 and 99.

    Reporting group values
    Vedolizumab 300 mg Vedolizumab 600 mg Total
    Number of subjects
    8 9 17
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    7 6 13
        From 65-84 years
    1 3 4
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    54.1 ± 10.45 59.0 ± 10.87 -
    Sex: Female, Male
    Units: Subjects
        Female
    6 4 10
        Male
    2 5 7
    Baseline Eastern Cooperative Oncology Group (ECOG) Status
    ECOG assessed participant's performance status on a 6 point scale: 0=Normal activity (fully active, able to carry on all predisease performance without restriction); 1=Symptoms but ambulatory (restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature); 2=In bed <50% of the time (ambulatory and capable of all self-care, but unable to carry out any work activities); 3=In bed >50% of the time (capable of only limited self-care); 4=100% bedridden (completely disabled, cannot carry on any selfcare, totally confined to bed or chair) 5=Dead.
    Units: Subjects
        Score = 0
    2 0 2
        Score = 1
    3 2 5
        Score = 2
    1 4 5
        Score = 3
    2 3 5
    Region of Enrollment
    Units: Subjects
        Belgium|
    2 2 4
        France|
    3 1 4
        Norway|
    0 1 1
        United States|
    3 5 8
    Race/Ethnicity, Customized
    Units: Subjects
        Not Hispanic or Latino
    6 9 15
        Not Reported
    2 0 2
    Race/Ethnicity, Customized
    Units: Subjects
        White
    7 9 16
        Not Reported
    1 0 1
    Height
    Units: cm
        arithmetic mean (standard deviation)
    170.3 ± 12.08 169.8 ± 7.87 -
    Weight
    Units: kg
        arithmetic mean (standard deviation)
    76.40 ± 16.900 74.01 ± 22.255 -

    End points

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    End points reporting groups
    Reporting group title
    Vedolizumab 300 mg
    Reporting group description
    Vedolizumab 300 mg, intravenous (IV) infusion, once on Days 1, 15, 43, 71 and 99.

    Reporting group title
    Vedolizumab 600 mg
    Reporting group description
    Vedolizumab 600 mg, IV infusion, once on Days 1, 15, 43, 71 and 99.

    Primary: Percentage of Participants with Overall Response (Partial Response [PR]+Very Good Partial Response [VGPR]+Complete Response [CR]) at Day 28

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    End point title
    Percentage of Participants with Overall Response (Partial Response [PR]+Very Good Partial Response [VGPR]+Complete Response [CR]) at Day 28 [1]
    End point description
    CR is defined as the resolution of all signs and symptoms of acute graft-versus-host-disease (GvHD). VGPR is defined as resolution of the signs and symptoms of the GvHD: 1) Skin: no rash, or residual erythematous rash involving <25% of the body surface, without bullae (excluding residual faint erythema and hyperpigmentation). 2) Liver: total serum bilirubin concentration <2 mg/dL or <25% of baseline at enrollment. 3) Gut: a) participant tolerates food or enteral feeding; b) predominantly formed stools; c) no overt gastrointestinal bleeding or abdominal cramping; d) no more than occasional nausea or vomiting. PR is defined as improvement of 1 GvHD stage in 1 or more organs without progression in any organ. Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.
    End point type
    Primary
    End point timeframe
    Day 28
    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: Statistical analysis was not planned for this endpoint.
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: percentage of participants
        number (confidence interval 95%)
    50.0 (15.7 to 84.3)
    22.2 (2.8 to 60.0)
    No statistical analyses for this end point

    Primary: Number of Participants who Experienced Serious Adverse Events (SAEs) Through Day 28

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    End point title
    Number of Participants who Experienced Serious Adverse Events (SAEs) Through Day 28 [2]
    End point description
    An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Safety analysis set (SAS) included all participants who received any amount of the study drug.
    End point type
    Primary
    End point timeframe
    From first dose up to Day 28
    Notes
    [2] - 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: Statistical analysis was not planned for this endpoint.
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: participants
    3
    4
    No statistical analyses for this end point

    Secondary: Percentage of Participants who Died in the Absence of Primary Malignancy Relapse After allo-HSCT at Month 6

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    End point title
    Percentage of Participants who Died in the Absence of Primary Malignancy Relapse After allo-HSCT at Month 6
    End point description
    Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: percentage of participants
        number (confidence interval 95%)
    50.0 (15.7 to 84.3)
    88.9 (68.4 to 100.0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Acute GvHD Complete Response (CR) at Day 28

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    End point title
    Percentage of Participants with Acute GvHD Complete Response (CR) at Day 28
    End point description
    CR is defined as the resolution of all signs and symptoms of acute GvHD. Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: percentage of participants
        number (confidence interval 95%)
    12.5 (0.3 to 52.7)
    0 (0 to 0)
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Intestinal Overall Response at Day 28

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    End point title
    Percentage of Participants with Intestinal Overall Response at Day 28
    End point description
    Symptoms of acute intestinal GvHD were measured using the BMT CTN-modified International Bone Marrow Transplant Registry Database (IBMTR) index. Intestinal overall response is either CR, VGPR or PR for intestine only. CR is defined as the resolution of all signs and symptoms of GvHD. VGPR is defined as resolution of the majority of signs and symptoms of intestinal GvHD: a) participant tolerates food or enteral feeding; b) predominantly formed stools; c) no overt gastrointestinal bleeding or abdominal cramping; d) no more than occasional nausea or vomiting. PR is defined as improvement of intestinal GvHD by at least 1 stage. Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Day 28
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: percentage of participants
        number (confidence interval 95%)
    62.5 (24.5 to 91.5)
    33.3 (7.5 to 70.1)
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Months 6 and 12

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    End point title
    Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Months 6 and 12
    End point description
    The Kaplan-Meier estimate reports the percentage of participants surviving at Months 6 and 12. 9999 = Data not available (NA), due to a low number of participants with events. Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Months 6 and 12
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: percentage of participants
    number (confidence interval 95%)
        Month 6|
    0.50 (0.15 to 0.77)
    0.11 (0.01 to 0.39)
        Month 12|
    9999 (9999 to 9999)
    9999 (9999 to 9999)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Alive Without GvHD or Primary Malignancy Relapse at Months 6 and 12

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    End point title
    Percentage of Participants Alive Without GvHD or Primary Malignancy Relapse at Months 6 and 12
    End point description
    Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    Months 6 and 12
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: percentage of participants
    number (not applicable)
        Month 6|
    37.5
    0
        Month 12|
    0
    0
    No statistical analyses for this end point

    Secondary: Total Dose of Steroids Administered

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    End point title
    Total Dose of Steroids Administered
    End point description
    Total Steroids administered in mg/kg/day of methylprednisolone or equivalent. Efficacy analysis set included all participants from the safety set who had baseline efficacy assessment and at least one post-baseline efficacy assessment.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug up to Months 6 and 12
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: mg/kg/day
    arithmetic mean (standard deviation)
        Month 6|
    0.862 ± 0.6397
    0.876 ± 0.4796
        Month 12|
    0.829 ± 0.6611
    0.876 ± 0.4798
    No statistical analyses for this end point

    Secondary: Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)

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    End point title
    Number of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)
    End point description
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. SAS included all participants who received any amount of the study drug.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug to 18 weeks after last dose (Up to Week 32)
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: participants
    8
    9
    No statistical analyses for this end point

    Secondary: Number of Participants who Experienced Serious Adverse Events (SAEs) Through Week 32

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    End point title
    Number of Participants who Experienced Serious Adverse Events (SAEs) Through Week 32
    End point description
    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An SAE is defined as an untoward medical occurrence, significant hazard, contraindication, side effect or precaution that at any dose: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. SAS included all participants who received any amount of the study drug.
    End point type
    Secondary
    End point timeframe
    From first dose of study drug to 18 weeks after last dose (Up to Week 32)
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: participants
    6
    9
    No statistical analyses for this end point

    Secondary: Number of Participants with Markedly Abnormal Laboratory Parameters Values

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    End point title
    Number of Participants with Markedly Abnormal Laboratory Parameters Values
    End point description
    Clinical laboratory parameters included tests for chemistry, hematology, urinalysis. Markedly abnormal values during treatment period were:alanine aminotransferase (ALT)>3.0 U/L*upper limit of normal(ULN),albumin<25 g/L*lower limit of normal(LLN),alkaline phosphatase>3.0 U/L*ULN,aspartate aminotransferase >3.0 U/L*ULN,bilirubin>2 umol/L*ULN,blood urea nitrogen(BUN) >10.7 mmol/L,calcium <1.75 mmol/L, >2.88 mmol/L,chloride<75 mmol/L, >126 mmol/L,creatinine >177umol/L,gamma glutamyl transferase (GGT) >3 U/L*ULN,glucose <2.8 mmol/L, >19.4 mmol/L,phosphate <0.52 mmol/L, >2.10 mmol/L,potassium<3 mmol/L, >6 mmol/L,sodium <130 mmol/L, >150 mmol/L,basophils >3(10^9/L)*ULN,eosinophils >2(10^9/L)*ULN,hematocrit (%) <0.8*LLN, >1.2*ULN,hemoglobin <0.8 g/L*LLN, >1.2 g/L*ULN,leukocytes <0.5 (10^9/L)*LLN, >1.5 (10^9/L)*ULN,lymphocytes <0.5 (10^9/L)*LLN, >1.5(10^9/L)*ULN,monocytes >2 (10^9/L)*ULN,neutrophils <0.5(10^9/L)*LLN, >1.5 (10^9/L)*ULN,platelets <75(10^9/L), >600(10^9/L). Safety analysis set.
    End point type
    Secondary
    End point timeframe
    From Baseline up to last dose of study drug (Day 99)
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: participants
        ALT >3.0 U/L*ULN|
    4
    0
        Albumin <25 g/L*LLN|
    4
    8
        Alkaline phosphatase >3.0 U/L*ULN|
    1
    0
        Aspartate aminotransferase >3.0 U/L*ULN|
    1
    0
        Bilirubin >2 umol/L*ULN|
    1
    2
        BUN >10.7 mmol/L|
    3
    6
        Calcium <1.75 mmol/L|
    0
    3
        Calcium >2.88 mmol/L|
    0
    0
        Chloride <75 mmol/L|
    0
    0
        Chloride >126 mmol/L|
    0
    0
        Creatinine >177umol/L|
    0
    1
        GGT >3 U/L*ULN|
    5
    2
        Glucose <2.8 mmol/L|
    0
    0
        Glucose >19.4 mmol/L|
    1
    0
        Phosphate <0.52 mmol/L|
    0
    0
        Phosphate >2.10 mmol/L|
    0
    1
        Potassium <3 mmol/L|
    1
    0
        Potassium >6 mmol/L|
    0
    0
        Sodium <130 mmol/L|
    0
    0
        Sodium >150 mmol/L|
    0
    0
        Basophils >3(10^9/L)*ULN|
    0
    0
        Eosinophils >2(10^9/L)*ULN|
    0
    0
        Hematocrit (%) <0.8*LLN|
    7
    8
        Hematocrit (%) >1.2*ULN|
    0
    0
        Hemoglobin <0.8 g/L*LLN|
    7
    8
        Hemoglobin >1.2 g/L*ULN|
    0
    0
        Leukocytes <0.5 (10^9/L)*LLN|
    3
    7
        Leukocytes >1.5 (10^9/L)*ULN|
    1
    0
        Lymphocytes <0.5 (10^9/L)*LLN|
    7
    9
        Lymphocytes >1.5(10^9/L)*ULN|
    0
    0
        Monocytes >2 (10^9/L)*ULN|
    0
    1
        Neutrophils <0.5(10^9/L)*LLN|
    0
    3
        Neutrophils >1.5 (10^9/L)*ULN|
    1
    1
        Platelets <75(10^9/L)|
    8
    9
        Platelets >600(10^9/L)|
    0
    0
    No statistical analyses for this end point

    Secondary: Number of Participants with Markedly Abnormal Vital Signs

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    End point title
    Number of Participants with Markedly Abnormal Vital Signs
    End point description
    Vital signs included heart rate, respiratory rate, systolic and diastolic blood pressure, temperature and weight. The vital sign values outside the range: systolic blood pressure (SBP) <85 mmHg and change from Baseline (BL) <=-20 mmHg, >180 mmHg and change from Baseline >=20 mmHg,diastolic blood pressure (DBP) <50 mmHg and change from Baseline <=-15 mmHg, >110 mmHg and change from Baseline >=15 mmHg, heart rate <50 beats per minute (bpm),>120 beats per minute, temperature <35.6 Degree C, >37.7 Degree C and weight change from Baseline <=-7 % and weight change from Baseline >=7 % assessed during treatment period were considered markedly abnormal. SAS included all participants who received any amount of the study drug.
    End point type
    Secondary
    End point timeframe
    From Baseline up to last dose of study drug (Day 99)
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    9
    Units: participants
        SBP <85 mmHg and change from BL <=-20 mmHg|
    0
    0
        SBP >180 mmHg and change from BL >=20 mmHg|
    1
    0
        DBP <50 mmHg and change from BL<=-15 mmHg|
    0
    0
        DBP >110 mmHg and change from BL>=15 mmHg|
    0
    0
        Heart Rate <50 bpm|
    0
    0
        Heart Rate >120 bpm|
    0
    1
        Temperature <35.6 Degree C|
    1
    3
        Temperature >37.7 Degree C|
    0
    0
        Weight change from BL <=-7 %|
    4
    2
        Weight change from BL >=7 %|
    3
    1
    No statistical analyses for this end point

    Secondary: Ctrough: Trough Serum Concentrations of Vedolizumab

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    End point title
    Ctrough: Trough Serum Concentrations of Vedolizumab
    End point description
    Pharmacokinetic (PK) set included all participants from the safety set with at least 1 post dose PK sample collected.
    End point type
    Secondary
    End point timeframe
    Day 99 (pre-dose)
    End point values
    Vedolizumab 300 mg Vedolizumab 600 mg
    Number of subjects analysed
    8
    8
    Units: ug/mL
        arithmetic mean (standard deviation)
    40.2 ± 37.2
    12.3 ± 5.49
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study drug to 18 weeks after the last dose of study drug (Up to approximately 32 weeks)
    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
    21.0
    Reporting groups
    Reporting group title
    Vedolizumab 300 mg
    Reporting group description
    Vedolizumab 300 mg, IV infusion, once on Days 1, 15, 43, 71 and 99.

    Reporting group title
    Vedolizumab 600 mg
    Reporting group description
    Vedolizumab 600 mg, IV infusion, once on Days 1, 15, 43, 71 and 99.

    Serious adverse events
    Vedolizumab 300 mg Vedolizumab 600 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 8 (75.00%)
    9 / 9 (100.00%)
         number of deaths (all causes)
    4
    9
         number of deaths resulting from adverse events
    2
    6
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         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
    Post procedural complication
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         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
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Graft versus host disease
         subjects affected / exposed
    0 / 8 (0.00%)
    3 / 9 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    2 / 2
    Acute graft versus host disease
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute graft versus host disease in intestine
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute graft versus host disease in liver
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Graft versus host disease in gastrointestinal tract
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Blood and lymphatic system disorders
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Febrile neutropenia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Skin and subcutaneous tissue disorders
    Swelling face
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Peritonitis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bacterial sepsis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Citrobacter sepsis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus colitis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Enterococcal sepsis
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Escherichia infection
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mediastinitis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pneumonia necrotising
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 8 (25.00%)
    1 / 9 (11.11%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Vedolizumab 300 mg Vedolizumab 600 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    8 / 8 (100.00%)
    9 / 9 (100.00%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 8 (12.50%)
    2 / 9 (22.22%)
         occurrences all number
    2
    4
    Haematoma
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Hypertension
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Jugular vein thrombosis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Venoocclusive disease
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Anogenital warts
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    2 / 8 (25.00%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Graft versus host disease in gastrointestinal tract
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    2
    Graft versus host disease in skin
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Acute graft versus host disease in intestine
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Acute graft versus host disease in skin
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Oedema peripheral
         subjects affected / exposed
    3 / 8 (37.50%)
    3 / 9 (33.33%)
         occurrences all number
    3
    6
    Fatigue
         subjects affected / exposed
    0 / 8 (0.00%)
    3 / 9 (33.33%)
         occurrences all number
    0
    3
    Pyrexia
         subjects affected / exposed
    1 / 8 (12.50%)
    2 / 9 (22.22%)
         occurrences all number
    1
    2
    Generalised oedema
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Asthenia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Catheter site haemorrhage
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Chills
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Injection site pain
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Oedema
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Pain
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Anxiety
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Oedema genital
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Laceration
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Blood bilirubin increased
         subjects affected / exposed
    2 / 8 (25.00%)
    2 / 9 (22.22%)
         occurrences all number
    5
    5
    Platelet count decreased
         subjects affected / exposed
    2 / 8 (25.00%)
    1 / 9 (11.11%)
         occurrences all number
    8
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 8 (12.50%)
    2 / 9 (22.22%)
         occurrences all number
    1
    2
    White blood cell count decreased
         subjects affected / exposed
    1 / 8 (12.50%)
    2 / 9 (22.22%)
         occurrences all number
    1
    6
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Blood urea increased
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    3
    Blood alkaline phosphatase increased
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    BK polyomavirus test positive
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Blood beta-D-glucan increased
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Blood creatine increased
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Blood pressure decreased
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Cytomegalovirus test positive
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Liver function test abnormal
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Neutrophil count decreased
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    5
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Urine output decreased
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Vitamin D decreased
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Weight decreased
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Pericardial effusion
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Sinus bradycardia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 8 (12.50%)
    2 / 9 (22.22%)
         occurrences all number
    1
    2
    Cough
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Epistaxis
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    2
    Hypoxia
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    3
    Pleural effusion
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Respiratory failure
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Aspiration
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Atelectasis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Dyspnoea exertional
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Hiccups
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Increased bronchial secretion
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Pulmonary oedema
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Upper-airway cough syndrome
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 8 (50.00%)
    3 / 9 (33.33%)
         occurrences all number
    6
    4
    Neutropenia
         subjects affected / exposed
    1 / 8 (12.50%)
    3 / 9 (33.33%)
         occurrences all number
    1
    5
    Thrombocytopenia
         subjects affected / exposed
    2 / 8 (25.00%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Aplasia pure red cell
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 8 (12.50%)
    3 / 9 (33.33%)
         occurrences all number
    1
    3
    Headache
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Somnolence
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    2
    Ageusia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Clonus
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Embolic stroke
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Head titubation
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Neuropathy peripheral
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Tremor
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Vision blurred
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Dry eye
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Eye pruritus
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Lacrimation increased
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 8 (12.50%)
    2 / 9 (22.22%)
         occurrences all number
    1
    2
    Nausea
         subjects affected / exposed
    3 / 8 (37.50%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Abdominal pain
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Dyspepsia
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Vomiting
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Ascites
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    3
    0
    Dry mouth
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Gingival pain
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Ileus paralytic
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Mouth ulceration
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Oral mucosa haematoma
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Proctalgia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Rectal haemorrhage
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Stomatitis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Tongue discolouration
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Pollakiuria
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Proteinuria
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Urinary retention
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Haematuria
         subjects affected / exposed
    2 / 8 (25.00%)
    0 / 9 (0.00%)
         occurrences all number
    2
    0
    Skin and subcutaneous tissue disorders
    Pain of skin
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    2
    Alopecia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Angioedema
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Blister
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Dry skin
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Erythema
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Ingrowing nail
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Lichen planus
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Onychoclasis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Rash macular
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Muscular weakness
         subjects affected / exposed
    2 / 8 (25.00%)
    2 / 9 (22.22%)
         occurrences all number
    2
    3
    Pain in extremity
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Arthralgia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Back pain
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Bone pain
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Myalgia
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Endocrine disorders
    Adrenal insufficiency
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    3 / 8 (37.50%)
    5 / 9 (55.56%)
         occurrences all number
    9
    7
    Hyperglycaemia
         subjects affected / exposed
    3 / 8 (37.50%)
    2 / 9 (22.22%)
         occurrences all number
    3
    2
    Hypoalbuminaemia
         subjects affected / exposed
    2 / 8 (25.00%)
    3 / 9 (33.33%)
         occurrences all number
    2
    4
    Hypomagnesaemia
         subjects affected / exposed
    1 / 8 (12.50%)
    3 / 9 (33.33%)
         occurrences all number
    1
    4
    Hypocalcaemia
         subjects affected / exposed
    1 / 8 (12.50%)
    2 / 9 (22.22%)
         occurrences all number
    1
    5
    Hypermagnesaemia
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    2
    Acidosis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Diabetes mellitus
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Electrolyte imbalance
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Fluid imbalance
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Hypernatraemia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    2
    Hypertriglyceridaemia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Malnutrition
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Cytomegalovirus infection
         subjects affected / exposed
    2 / 8 (25.00%)
    1 / 9 (11.11%)
         occurrences all number
    2
    1
    Enterococcal infection
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    BK virus infection
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Klebsiella infection
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    2
    Staphylococcal infection
         subjects affected / exposed
    0 / 8 (0.00%)
    2 / 9 (22.22%)
         occurrences all number
    0
    2
    Aspergillus infection
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Urinary tract infection enterococcal
         subjects affected / exposed
    1 / 8 (12.50%)
    1 / 9 (11.11%)
         occurrences all number
    1
    1
    Clostridium difficile infection
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Clostridial infection
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Corona virus infection
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Cytomegalovirus colitis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Device related infection
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Enterobacter infection
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Escherichia infection
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Infection
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Mastoiditis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Otitis externa
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Pseudomonas infection
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Septic shock
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Sinusitis
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 8 (0.00%)
    1 / 9 (11.11%)
         occurrences all number
    0
    1
    Urinary tract infection bacterial
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Urosepsis
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0
    Vaginal infection
         subjects affected / exposed
    1 / 8 (12.50%)
    0 / 9 (0.00%)
         occurrences all number
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Nov 2017
    The following changes were made as per amendment 2 – • Clarified inclusion/exclusion criteria. • Clarify efficacy analyses. • Modified conduct of the interim analysis.

    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
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
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