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    Clinical Trial Results:
    A participant and investigator-blinded, randomized, placebo-controlled Phase 2a study to investigate the pharmacokinetics, pharmacodynamics, safety and tolerability of TIN816 in patients with sepsis-associated acute kidney injury

    Summary
    EudraCT number
    		 2022-000887-23
    Trial protocol
    		 ES   FR   DE   BE   HU  
    Global end of trial date
    25 Apr 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Apr 2025
    First version publication date
    30 Apr 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CTIN816B12201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05507437
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharmaceuticals
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Novartis Pharma AG, Clinical Disclosure Office, 41 613241111, novartis.email@novartis.com
    Scientific contact
    Novartis Pharma AG, Clinical Disclosure Office, 41 613241111, novartis.email@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    25 Apr 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Apr 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to assess the pharmacokinetics (PK) of TIN816 with a single dose of intravenous (IV) infusion in hospitalized adult participants with diagnosis of sepsis-associated acute kidney injury.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    22 Nov 2022
    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
    Belgium: 8
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    France: 9
    Country: Number of subjects enrolled
    Spain: 1
    Country: Number of subjects enrolled
    Germany: 1
    Worldwide total number of subjects
    20
    EEA total number of subjects
    20
    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)
    7
    From 65 to 84 years
    12
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants took part in 7 investigative sites in 5 countries.

    Pre-assignment
    Screening details
    		 The study consisted of a screening period up to 48 hours.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 TIN816
    Arm description
    		 TIN816 2 mg/kg intravenous dose on Day 1.
    Arm type
    		 Experimental

    Investigational medicinal product name
    TIN816
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single i.v. infusion of TIN816 administered at a dose of 2 mg/kg.

    Arm title
    		 Placebo
    Arm description
    		 Placebo intravenous dose on Day 1
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Single i.v. infusion of placebo.

    Number of subjects in period 1
    		TIN816 Placebo
    Started
    16
    4
    Completed
    12
    3
    Not completed
    4
    1
         Consent withdrawn by subject
    1
    1
         Adverse event
    3
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    TIN816
    Reporting group description
    		 TIN816 2 mg/kg intravenous dose on Day 1.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo intravenous dose on Day 1

    Reporting group values
    		 TIN816 Placebo Total
    Number of subjects
    		 16 4 20
    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)
    		 6 1 7
        From 65-84 years
    		 10 2 12
        85 years and over
    		 0 1 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 66.25 ( 12.250 ) 68.0 ( 19.950 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 3 1 4
        Male
    		 13 3 16
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 2 1 3
        Not Reported
    		 14 3 17

    End points

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    End points reporting groups
    Reporting group title
    TIN816
    Reporting group description
    		 TIN816 2 mg/kg intravenous dose on Day 1.

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo intravenous dose on Day 1

    Primary: Maximum serum concentration (Cmax) of TIN816

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    End point title
    		 Maximum serum concentration (Cmax) of TIN816 [1] [2]
    End point description
    Cmax is defined as the maximum (peak) observed concentration following a dose. TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.
    End point type
    Primary
    End point timeframe
    Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90
    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: only analyzed descriptively.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK Endpoint not analyzed for participants on placebo
    End point values
    		 TIN816
    Number of subjects analysed
    16
    Units: ug/mL
        geometric mean (geometric coefficient of variation)
    40.8 ( 36.7 )
    No statistical analyses for this end point

    Primary: Area under serum concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) of TIN816

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    End point title
    		 Area under serum concentration-time curve from time zero to the last measurable concentration sampling time (AUClast) of TIN816 [3] [4]
    End point description
    AUClast is the area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (tlast) of TIN816. TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.
    End point type
    Primary
    End point timeframe
    Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: only analyzed descriptively.
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK Endpoint not analyzed for participants on placebo
    End point values
    		 TIN816
    Number of subjects analysed
    16
    Units: day*ug/mL
        geometric mean (geometric coefficient of variation)
    99.9 ( 49.0 )
    No statistical analyses for this end point

    Primary: Terminal elimination half-life (T1/2) of TIN816

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    End point title
    		 Terminal elimination half-life (T1/2) of TIN816 [5] [6]
    End point description
    T1/2 is the elimination half-life associated with the terminal slope. TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.
    End point type
    Primary
    End point timeframe
    Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90
    Notes
    [5] - 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: only analyzed descriptively.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK Endpoint not analyzed for participants on placebo
    End point values
    		 TIN816
    Number of subjects analysed
    13
    Units: Day
        geometric mean (geometric coefficient of variation)
    5.70 ( 14.8 )
    No statistical analyses for this end point

    Primary: Total body clearance (CL) of TIN816

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    End point title
    		 Total body clearance (CL) of TIN816 [7] [8]
    End point description
    CL is the total body clearance of TIN816 from the serum following intravenous administration (volume x time-1). TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.
    End point type
    Primary
    End point timeframe
    Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90
    Notes
    [7] - 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: only analyzed descriptively.
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK Endpoint not analyzed for participants on placebo
    End point values
    		 TIN816
    Number of subjects analysed
    13
    Units: Liter/day/kg
        geometric mean (geometric coefficient of variation)
    0.0189 ( 24.7 )
    No statistical analyses for this end point

    Primary: The apparent volume of distribution (Vz) of TIN816

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    End point title
    		 The apparent volume of distribution (Vz) of TIN816 [9] [10]
    End point description
    Vz is the apparent volume of distribution during terminal phase following intravenous administration. TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.
    End point type
    Primary
    End point timeframe
    Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90
    Notes
    [9] - 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: only analyzed descriptively.
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK Endpoint not analyzed for participants on placebo
    End point values
    		 TIN816
    Number of subjects analysed
    13
    Units: Liter/kg
        geometric mean (geometric coefficient of variation)
    0.155 ( 31.7 )
    No statistical analyses for this end point

    Primary: Area under the serum concentration-time curve from time zero extrapolated to infinity (AUC[0-inf]) of TIN816

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    End point title
    		 Area under the serum concentration-time curve from time zero extrapolated to infinity (AUC[0-inf]) of TIN816 [11] [12]
    End point description
    The AUC from time zero to infinity (mass x time x volume-1). TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.
    End point type
    Primary
    End point timeframe
    Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90
    Notes
    [11] - 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: only analyzed descriptively.
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK Endpoint not analyzed for participants on placebo
    End point values
    		 TIN816
    Number of subjects analysed
    13
    Units: day*ug/mL
        geometric mean (geometric coefficient of variation)
    104 ( 47.7 )
    No statistical analyses for this end point

    Primary: Time to reach maximum serum concentration (Tmax) of TIN816

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    End point title
    		 Time to reach maximum serum concentration (Tmax) of TIN816 [13] [14]
    End point description
    Tmax is the time to reach maximum (peak) drug concentration after single-dose administration (time). TIN816 serum concentrations were determined using the actual recorded sampling times and non-compartmental method with Phoenix WinNonlin (Version 8.3). TIN816 concentrations were determined by a validated ligand binding assay with a lower limit of quantification (LLOQ) of 10 ng/mL.
    End point type
    Primary
    End point timeframe
    Day 1 (Pre-dose and 2 hours), Day 2, Day 3, Day 5, Day 8, Day 14, Day 30, Day 60 and Day 90
    Notes
    [13] - 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: only analyzed descriptively.
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: PK Endpoint not analyzed for participants on placebo
    End point values
    		 TIN816
    Number of subjects analysed
    16
    Units: Day
        median (full range (min-max))
    0.0868 (0.0597 to 0.163)
    No statistical analyses for this end point

    Secondary: Number of participants with treatment emergent adverse events (AEs) and serious adverse events (SAEs)

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    End point title
    		 Number of participants with treatment emergent adverse events (AEs) and serious adverse events (SAEs)
    End point description
    Number of participants with treatment emergent AEs (any AE regardless of seriousness) and SAEs.
    End point type
    Secondary
    End point timeframe
    Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 90 days.
    End point values
    		 TIN816 Placebo
    Number of subjects analysed
    16
    4
    Units: Participants
        Adverse events
    14
    4
        Serious Adverse events
    11
    1
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from first dose of study treatment until end of study treatment plus follow up period, up to a maximum duration of approximately 90 days.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.0
    Reporting groups
    Reporting group title
    TIN816
    Reporting group description
    		 TIN816

    Reporting group title
    All Patients
    Reporting group description
    		 All Patients

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Serious adverse events
    		 TIN816 All Patients Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    11 / 16 (68.75%)
    12 / 20 (60.00%)
    1 / 4 (25.00%)
         number of deaths (all causes)
    3
    3
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Distributive shock
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardio-respiratory arrest
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haematoma
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    Acute respiratory failure
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Toxic epidermal necrolysis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal tubular necrosis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute kidney injury
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infectious pleural effusion
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 TIN816 All Patients Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 16 (87.50%)
    18 / 20 (90.00%)
    4 / 4 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Plasma cell myeloma
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 20 (10.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    2
    1
    Haemorrhage
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Haemodynamic instability
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Deep vein thrombosis
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 20 (10.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    2
    1
    Pelvic venous thrombosis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hypotension
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Shock haemorrhagic
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hyperthermia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Chest pain
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Systemic inflammatory response syndrome
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Respiratory distress
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Respiratory acidosis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hypercapnia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Confusional state
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Delirium
         subjects affected / exposed
    2 / 16 (12.50%)
    3 / 20 (15.00%)
    1 / 4 (25.00%)
         occurrences all number
    2
    3
    1
    Insomnia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Cardiac disorders
    Stress cardiomyopathy
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Atrioventricular block first degree
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Atrial fibrillation
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Nervous system disorders
    Extrapyramidal disorder
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Intensive care unit acquired weakness
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Myoclonus
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    3 / 16 (18.75%)
    5 / 20 (25.00%)
    2 / 4 (50.00%)
         occurrences all number
    4
    6
    2
    Lymphopenia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Ear and labyrinth disorders
    Ear haemorrhage
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Eye disorders
    Phlyctenular keratoconjunctivitis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Constipation
         subjects affected / exposed
    3 / 16 (18.75%)
    3 / 20 (15.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    3
    0
    Diarrhoea
         subjects affected / exposed
    1 / 16 (6.25%)
    3 / 20 (15.00%)
    2 / 4 (50.00%)
         occurrences all number
    1
    3
    2
    Faecaloma
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Impaired gastric emptying
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Nausea
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Oesophagitis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Oral mucosal blistering
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Pancreatitis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hepatic cytolysis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Cholecystitis acute
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Pruritus
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Decubitus ulcer
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Renal failure
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Urinary retention
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Gouty arthritis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Musculoskeletal pain
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 20 (10.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Rhabdomyolysis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Bacteraemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    COVID-19
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Endocarditis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Herpes simplex reactivation
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Oral candidiasis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Oral herpes
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Pneumonia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Skin bacterial infection
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Systemic candida
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Urinary tract candidiasis
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Urinary tract infection
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    2
    2
    0
    Urosepsis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Clostridium difficile infection
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Metabolism and nutrition disorders
    Hyperkalaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hyperferritinaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Folate deficiency
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 20 (5.00%)
    1 / 4 (25.00%)
         occurrences all number
    0
    1
    1
    Hypernatraemia
         subjects affected / exposed
    3 / 16 (18.75%)
    4 / 20 (20.00%)
    1 / 4 (25.00%)
         occurrences all number
    3
    4
    1
    Hyperphosphataemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    3 / 16 (18.75%)
    3 / 20 (15.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    3
    0
    Hyperuricaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hypervolaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hypocalcaemia
         subjects affected / exposed
    3 / 16 (18.75%)
    3 / 20 (15.00%)
    0 / 4 (0.00%)
         occurrences all number
    3
    3
    0
    Hypokalaemia
         subjects affected / exposed
    2 / 16 (12.50%)
    3 / 20 (15.00%)
    1 / 4 (25.00%)
         occurrences all number
    2
    4
    2
    Hypomagnesaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    3 / 16 (18.75%)
    4 / 20 (20.00%)
    1 / 4 (25.00%)
         occurrences all number
    3
    4
    1
    Malnutrition
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 20 (10.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    2
    1
    Metabolic acidosis
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 20 (10.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    2
    1
    Vitamin C deficiency
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 20 (5.00%)
    0 / 4 (0.00%)
         occurrences all number
    1
    1
    0
    Vitamin D deficiency
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 20 (10.00%)
    1 / 4 (25.00%)
         occurrences all number
    1
    2
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

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

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

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