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    Clinical Trial Results:
    A randomized, double-blind, placebo-controlled, multi-center study to assess the safety and efficacy of individually titrated oral doses of runcaciguat in subjects with clinical diagnosis of chronic kidney disease with diabetes and/or hypertension and at least one cardiovascular comorbidity

    Summary
    EudraCT number
    		 2019-003297-53
    Trial protocol
    		 DE   DK   IT   FI   SE   ES   PL   AT   BE   BG   SK  
    Global end of trial date
    05 Apr 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Apr 2023
    First version publication date
    16 Apr 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    18748
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04507061
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bayer AG
    Sponsor organisation address
    Kaiser-Wilhelm-Allee, Leverkusen, Germany, D-51368
    Public contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.com
    Scientific contact
    Therapeutic Area Head, Bayer AG, clinical-trials-contact@bayer.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
    06 May 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Apr 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study is to investigate the change in albuminuria by urinary albumin-to-creatinine ratio (UACR) after treatment with titrated doses of runcaciguat given once daily from baseline to day 57 (±3). The secondary objective is to investigate the overall safety and tolerability of Runcaciguat.
    Protection of trial subjects
    The conduct of this clinical study met all local legal and regulatory requirements. The study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all subjects and/or their legally authorized representative. Participating subjects and/or their legally authorized representative signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
    Background therapy
    		 Standard of care therapy
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Sep 2020
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Austria: 9
    Country: Number of subjects enrolled
    Belgium: 15
    Country: Number of subjects enrolled
    Bulgaria: 44
    Country: Number of subjects enrolled
    Germany: 12
    Country: Number of subjects enrolled
    Denmark: 22
    Country: Number of subjects enrolled
    Spain: 36
    Country: Number of subjects enrolled
    Finland: 14
    Country: Number of subjects enrolled
    Israel: 30
    Country: Number of subjects enrolled
    Italy: 22
    Country: Number of subjects enrolled
    Poland: 1
    Country: Number of subjects enrolled
    Slovakia: 8
    Country: Number of subjects enrolled
    Sweden: 3
    Country: Number of subjects enrolled
    Ukraine: 27
    Worldwide total number of subjects
    243
    EEA total number of subjects
    186
    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)
    47
    From 65 to 84 years
    195
    85 years and over
    1

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Out of the 395 screened participants, 243 were randomized in 3 different strata and started treatment.

    Pre-assignment
    Screening details
    		 The reasons of 152 screen failure were, 135 participants not fulfilling inclusion or exclusion criteria, 14 withdrawal and 3 for other reasons.

    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, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Diabetic CKD with ≥3 months SGLT2 inhibitor, Runcaciguat
    Arm description
    		 Subjects of diabetic CKD with ≥3 months SGLT2 inhibitor randomized to this group were administered with the titrated doses (up to 120 mg or the maximum individual tolerated dose) of runcaciguat orally once a day on top of respective standard of care treatment in the morning.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Runcaciguat
    Investigational medicinal product code
    BAY1101042
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Individually titrated doses from 30 mg to 120 mg (or individually tolerated maximal dose) once daily

    Arm title
    		 Diabetic CKD with ≥3 months SGLT2 inhibitor, Placebo
    Arm description
    		 Subjects of diabetic CKD with ≥3 months SGLT2 inhibitor randomized to this group were administered with the titrated doses of matching placebo orally once a day on top of respective standard of care treatment in the morning.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    matching placebo

    Arm title
    		 Diabetic CKD without SGLT2 inhibitor, Runcaciguat
    Arm description
    		 Subjects of diabetic CKD without SGLT2 inhibitor randomized to this group were administered with the titrated doses (up to 120 mg or the maximum individual tolerated dose) of runcaciguat orally once a day on top of respective standard of care treatment in the morning.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Runcaciguat
    Investigational medicinal product code
    BAY1101042
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Individually titrated doses from 30 mg to 120 mg (or individually tolerated maximal dose) once daily

    Arm title
    		 Diabetic CKD without SGLT2 inhibitor, Placebo
    Arm description
    		 Subjects of diabetic CKD without SGLT2 inhibitor randomized to this group were administered with the titrated doses of matching placebo orally once a day on top of respective standard of care treatment in the morning.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    matching placebo

    Arm title
    		 Non-diabetic CKD, Runcaciguat
    Arm description
    		 Subjects of non-diabetic CKD randomized to this group were administered with the titrated doses (up to 120 mg or the maximum individual tolerated dose) of runcaciguat orally once a day on top of respective standard of care treatment in the morning.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Runcaciguat
    Investigational medicinal product code
    BAY1101042
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Individually titrated doses from 30 mg to 120 mg (or individually tolerated maximal dose) once daily

    Arm title
    		 Non-diabetic CKD, Placebo
    Arm description
    		 Subjects of non-diabetic CKD randomized to this group were administered with the titrated doses of matching placebo orally once a day on top of respective standard of care treatment in the morning.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    matching placebo

    Number of subjects in period 1
    		Diabetic CKD with ≥3 months SGLT2 inhibitor, Runcaciguat Diabetic CKD with ≥3 months SGLT2 inhibitor, Placebo Diabetic CKD without SGLT2 inhibitor, Runcaciguat Diabetic CKD without SGLT2 inhibitor, Placebo Non-diabetic CKD, Runcaciguat Non-diabetic CKD, Placebo
    Started
    65
    19
    66
    23
    53
    17
    Completed
    48
    15
    50
    21
    41
    14
    Not completed
    17
    4
    16
    2
    12
    3
         Adverse event, serious fatal
    -
    -
    1
    -
    -
    -
         COVID-19 pandemic
    -
    -
    -
    1
    -
    -
         Consent withdrawn by subject
    1
    -
    2
    -
    3
    1
         Adverse event, non-fatal
    12
    3
    10
    -
    7
    1
         Other
    1
    -
    -
    -
    -
    -
         Non-compliance with study drug
    1
    -
    2
    1
    1
    1
         Protocol deviation
    2
    1
    1
    -
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Diabetic CKD with ≥3 months SGLT2 inhibitor, Runcaciguat
    Reporting group description
    		 Subjects of diabetic CKD with ≥3 months SGLT2 inhibitor randomized to this group were administered with the titrated doses (up to 120 mg or the maximum individual tolerated dose) of runcaciguat orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Diabetic CKD with ≥3 months SGLT2 inhibitor, Placebo
    Reporting group description
    		 Subjects of diabetic CKD with ≥3 months SGLT2 inhibitor randomized to this group were administered with the titrated doses of matching placebo orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Diabetic CKD without SGLT2 inhibitor, Runcaciguat
    Reporting group description
    		 Subjects of diabetic CKD without SGLT2 inhibitor randomized to this group were administered with the titrated doses (up to 120 mg or the maximum individual tolerated dose) of runcaciguat orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Diabetic CKD without SGLT2 inhibitor, Placebo
    Reporting group description
    		 Subjects of diabetic CKD without SGLT2 inhibitor randomized to this group were administered with the titrated doses of matching placebo orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Non-diabetic CKD, Runcaciguat
    Reporting group description
    		 Subjects of non-diabetic CKD randomized to this group were administered with the titrated doses (up to 120 mg or the maximum individual tolerated dose) of runcaciguat orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Non-diabetic CKD, Placebo
    Reporting group description
    		 Subjects of non-diabetic CKD randomized to this group were administered with the titrated doses of matching placebo orally once a day on top of respective standard of care treatment in the morning.

    Reporting group values
    		 Diabetic CKD with ≥3 months SGLT2 inhibitor, Runcaciguat Diabetic CKD with ≥3 months SGLT2 inhibitor, Placebo Diabetic CKD without SGLT2 inhibitor, Runcaciguat Diabetic CKD without SGLT2 inhibitor, Placebo Non-diabetic CKD, Runcaciguat Non-diabetic CKD, Placebo Total
    Number of subjects
    		 65 19 66 23 53 17 243
    Age Categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: years
        geometric mean (standard deviation)
    		 69.3 ( 7.0 ) 70.2 ( 6.1 ) 71.8 ( 6.8 ) 71.7 ( 6.3 ) 69.9 ( 9.6 ) 69.8 ( 8.8 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 11 2 14 4 12 6 49
        Male
    		 54 17 52 19 41 11 194

    End points

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    End points reporting groups
    Reporting group title
    Diabetic CKD with ≥3 months SGLT2 inhibitor, Runcaciguat
    Reporting group description
    		 Subjects of diabetic CKD with ≥3 months SGLT2 inhibitor randomized to this group were administered with the titrated doses (up to 120 mg or the maximum individual tolerated dose) of runcaciguat orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Diabetic CKD with ≥3 months SGLT2 inhibitor, Placebo
    Reporting group description
    		 Subjects of diabetic CKD with ≥3 months SGLT2 inhibitor randomized to this group were administered with the titrated doses of matching placebo orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Diabetic CKD without SGLT2 inhibitor, Runcaciguat
    Reporting group description
    		 Subjects of diabetic CKD without SGLT2 inhibitor randomized to this group were administered with the titrated doses (up to 120 mg or the maximum individual tolerated dose) of runcaciguat orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Diabetic CKD without SGLT2 inhibitor, Placebo
    Reporting group description
    		 Subjects of diabetic CKD without SGLT2 inhibitor randomized to this group were administered with the titrated doses of matching placebo orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Non-diabetic CKD, Runcaciguat
    Reporting group description
    		 Subjects of non-diabetic CKD randomized to this group were administered with the titrated doses (up to 120 mg or the maximum individual tolerated dose) of runcaciguat orally once a day on top of respective standard of care treatment in the morning.

    Reporting group title
    Non-diabetic CKD, Placebo
    Reporting group description
    		 Subjects of non-diabetic CKD randomized to this group were administered with the titrated doses of matching placebo orally once a day on top of respective standard of care treatment in the morning.

    Subject analysis set title
    All CKD, Runcaciguat, PPS
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All CKD participants with Runcaciguat that fulfill the criteria of Per-protocol sets

    Subject analysis set title
    All CKD, Placebo, PPS
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All CKD participants with placebo that fulfill the criteria of Per-protocol set

    Subject analysis set title
    All CKD, Runcaciguat, SAF
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All CKD participants with Runcaciguat that fulfill the criteria for safety analysis

    Subject analysis set title
    All CKD, Placebo, SAF
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All CKD participants with placebo that fulfill the criteria for safety analysis

    Subject analysis set title
    All CKD, Runcaciguat, FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All CKD participants with Runcaciguat that fulfill the criteria of full analysis set

    Subject analysis set title
    All CKD, Placebo, FAS
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All CKD participants with Placebo that fulfill the criteria of full analysis set

    Primary: The mean change of the ratio of UACR at Day 22 (Visit 4), Day 29 (Visit 5) and Day 57 (Visit 7) versus the UACR at baseline

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    End point title
    		 The mean change of the ratio of UACR at Day 22 (Visit 4), Day 29 (Visit 5) and Day 57 (Visit 7) versus the UACR at baseline
    End point description
    Data presented in below table is geometric mean (geometric standard deviation), the correct form of SD range would be, for example, the lower value 220.1/3.0 and the upper value 220.1*3.0 instead of 220.1 (± 3.0) which is not properly displayed due to database constraints.
    End point type
    Primary
    End point timeframe
    at baseline, Day 22 (Visit 4), Day 29 (Visit 5) and Day 57 (Visit 7)
    End point values
    		 Diabetic CKD with ≥3 months SGLT2 inhibitor, Runcaciguat Diabetic CKD with ≥3 months SGLT2 inhibitor, Placebo Diabetic CKD without SGLT2 inhibitor, Runcaciguat Diabetic CKD without SGLT2 inhibitor, Placebo Non-diabetic CKD, Runcaciguat Non-diabetic CKD, Placebo All CKD, Runcaciguat, PPS All CKD, Placebo, PPS
    Number of subjects analysed
    44
    12
    44
    19
    37
    10
    125
    41
    Units: Not Applicable
    geometric mean (standard deviation)
        Baseline
    220.1 ( 3.0 )
    181.0 ( 3.6 )
    244.5 ( 3.2 )
    187.6 ( 3.3 )
    227.8 ( 2.7 )
    150.4 ( 3.7 )
    230.7 ( 2.9 )
    175.9 ( 3.4 )
        Day 22 (Visit 4)
    122.6 ( 4.8 )
    189.4 ( 3.3 )
    145.5 ( 3.7 )
    179.9 ( 4.5 )
    125.9 ( 3.9 )
    75.7 ( 6.2 )
    131.1 ( 4.1 )
    147.9 ( 4.5 )
        Day 29 (Visit 5)
    124.9 ( 4.6 )
    254.1 ( 3.1 )
    144.6 ( 3.7 )
    215.9 ( 4.0 )
    110.3 ( 4.1 )
    43.8 ( 10.5 )
    126.8 ( 4.1 )
    153.5 ( 5.6 )
        Day 57 (Visit 7)
    148.3 ( 3.8 )
    174.0 ( 3.4 )
    144.7 ( 3.4 )
    202.5 ( 3.5 )
    123.1 ( 4.0 )
    61.1 ( 8.6 )
    139.0 ( 3.7 )
    144.6 ( 4.7 )
    Statistical analysis title
    		 Runcaciguat/Placebo, diabetic CKD with inhibitor
    Statistical analysis description
    Bayesian analysis of treatment effect, the average geometric mean ratio to baseline of Visit 4, 5, 7, diabetic CKD with >= 3 months SGLT2 inhibitor (per protocol set)
    Comparison groups
    Diabetic CKD with ≥3 months SGLT2 inhibitor, Runcaciguat v Diabetic CKD with ≥3 months SGLT2 inhibitor, Placebo
    Number of subjects included in analysis
    56
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 geometric mean ratio
    Point estimate
    0.53
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 0.7
    Statistical analysis title
    		 Runcaciguat/Placebo, All CKD
    Statistical analysis description
    Bayesian analysis of treatment effect, the average geometric mean ratio to baseline of Visit 4, 5, 7, all CKD (per protocol set)
    Comparison groups
    All CKD, Runcaciguat, PPS v All CKD, Placebo, PPS
    Number of subjects included in analysis
    166
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 geometric mean ratio
    Point estimate
    0.676
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.584
         upper limit
    		 0.782
    Statistical analysis title
    		 Runcaciguat/Placebo, non-diabetic CKD
    Statistical analysis description
    Bayesian analysis of treatment effect, the average geometric mean ratio to baseline of Visit 4, 5, 7, Non-diabetic CKD (per protocol set)
    Comparison groups
    Non-diabetic CKD, Runcaciguat v Non-diabetic CKD, Placebo
    Number of subjects included in analysis
    47
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 geometric mean ratio
    Point estimate
    1.307
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.906
         upper limit
    		 1.889
    Statistical analysis title
    		 Runcaciguat/Placebo, diabetic CKD w/o inhibitor
    Statistical analysis description
    Bayesian analysis of treatment effect, the average geometric mean ratio to baseline of Visit 4, 5, 7, diabetic CKD without SGLT2 inhibitor (per protocol set)
    Comparison groups
    Diabetic CKD without SGLT2 inhibitor, Runcaciguat v Diabetic CKD without SGLT2 inhibitor, Placebo
    Number of subjects included in analysis
    63
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 geometric mean ratio
    Point estimate
    0.546
    Confidence interval
         level
    		 80%
         sides
    2-sided
         lower limit
    		 0.479
         upper limit
    		 0.622

    Secondary: Percentage of subjects with treatment emergent adverse event (TEAE)

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    End point title
    		 Percentage of subjects with treatment emergent adverse event (TEAE)
    End point description
    Adverse events will be considered as treatment-emergent if they occur after the first study intervention intake and until 7 (calendar) days after last study drug intake.
    End point type
    Secondary
    End point timeframe
    From first treatment administration up to 7 days after end of treatment
    End point values
    		 Diabetic CKD with ≥3 months SGLT2 inhibitor, Runcaciguat Diabetic CKD with ≥3 months SGLT2 inhibitor, Placebo Diabetic CKD without SGLT2 inhibitor, Runcaciguat Diabetic CKD without SGLT2 inhibitor, Placebo Non-diabetic CKD, Runcaciguat Non-diabetic CKD, Placebo All CKD, Runcaciguat, SAF All CKD, Placebo, SAF
    Number of subjects analysed
    65 [1]
    19 [2]
    66 [3]
    23 [4]
    53 [5]
    17 [6]
    184 [7]
    59 [8]
    Units: percentage
        number (not applicable)
    67.7
    57.9
    77.3
    60.9
    60.4
    35.3
    69.0
    52.5
    Notes
    [1] - SAF
    [2] - SAF
    [3] - SAF
    [4] - SAF
    [5] - SAF
    [6] - SAF
    [7] - SAF
    [8] - SAF
    No statistical analyses for this end point

    Secondary: Number of subjects with early discontinuations

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    End point title
    		 Number of subjects with early discontinuations
    End point description
    End point type
    Secondary
    End point timeframe
    From first treatment administration up to 7 days after end of treatment
    End point values
    		 Diabetic CKD with ≥3 months SGLT2 inhibitor, Runcaciguat Diabetic CKD with ≥3 months SGLT2 inhibitor, Placebo Diabetic CKD without SGLT2 inhibitor, Runcaciguat Diabetic CKD without SGLT2 inhibitor, Placebo Non-diabetic CKD, Runcaciguat Non-diabetic CKD, Placebo All CKD, Runcaciguat, SAF All CKD, Placebo, SAF
    Number of subjects analysed
    65 [9]
    19 [10]
    66 [11]
    23 [12]
    53 [13]
    17 [14]
    184
    59
    Units: subjects
    17
    4
    16
    2
    12
    3
    45
    9
    Notes
    [9] - SAF
    [10] - SAF
    [11] - SAF
    [12] - SAF
    [13] - SAF
    [14] - SAF
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events will be considered as treatment-emergent if they occur after the first study intervention intake and until 7 (calendar) days after last study drug intake.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Pooled analysis group of all CKD subjects who were administered with matching placebo.

    Reporting group title
    Runcaciguat
    Reporting group description
    		 Pooled analysis group of all CKD subjects who were administered with runcaciguat.

    Serious adverse events
    		 Placebo Runcaciguat
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 59 (8.47%)
    12 / 184 (6.52%)
         number of deaths (all causes)
    1
    1
         number of deaths resulting from adverse events
    1
    1
    Injury, poisoning and procedural complications
    Vascular graft occlusion
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Leg amputation
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis bullous
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Typhoid fever
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo Runcaciguat
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    30 / 59 (50.85%)
    123 / 184 (66.85%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Melanocytic naevus
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Eyelid naevus
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Vascular disorders
    Peripheral vascular disorder
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Hypertension
         subjects affected / exposed
    1 / 59 (1.69%)
    7 / 184 (3.80%)
         occurrences all number
    1
    8
    Hypotension
         subjects affected / exposed
    0 / 59 (0.00%)
    8 / 184 (4.35%)
         occurrences all number
    0
    13
    Intermittent claudication
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Orthostatic hypotension
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Pallor
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Surgical and medical procedures
    Endodontic procedure
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Knee arthroplasty
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Therapeutic nerve ablation
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    2
    0
    Vitrectomy
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 59 (0.00%)
    6 / 184 (3.26%)
         occurrences all number
    0
    6
    Chills
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Discomfort
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Fatigue
         subjects affected / exposed
    3 / 59 (5.08%)
    11 / 184 (5.98%)
         occurrences all number
    3
    11
    Feeling abnormal
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Feeling cold
         subjects affected / exposed
    0 / 59 (0.00%)
    5 / 184 (2.72%)
         occurrences all number
    0
    5
    Feeling hot
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Medical device site erythema
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Oedema
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    3
    Oedema peripheral
         subjects affected / exposed
    2 / 59 (3.39%)
    22 / 184 (11.96%)
         occurrences all number
    2
    25
    Peripheral swelling
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    1 / 59 (1.69%)
    2 / 184 (1.09%)
         occurrences all number
    1
    2
    Unevaluable event
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Pelvic pain
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Bronchial irritation
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Cough
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Dyspnoea
         subjects affected / exposed
    1 / 59 (1.69%)
    5 / 184 (2.72%)
         occurrences all number
    1
    5
    Epistaxis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Hiccups
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Nasal congestion
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Productive cough
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Restlessness
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Poor quality sleep
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Mood altered
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Insomnia
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    3
    Disorientation
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Agitation
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    2 / 59 (3.39%)
    4 / 184 (2.17%)
         occurrences all number
    2
    4
    Blood fibrinogen increased
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Blood glucose fluctuation
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Blood pressure decreased
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 184 (0.54%)
         occurrences all number
    1
    1
    Blood pressure increased
         subjects affected / exposed
    0 / 59 (0.00%)
    5 / 184 (2.72%)
         occurrences all number
    0
    7
    Colonoscopy
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Culture urine positive
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Electrocardiogram PR prolongation
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Endoscopy upper gastrointestinal tract
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Weight increased
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    3
    Transaminases increased
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    2
    Product residue present
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    International normalised ratio decreased
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Glutamate dehydrogenase increased
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Glomerular filtration rate decreased
         subjects affected / exposed
    0 / 59 (0.00%)
    5 / 184 (2.72%)
         occurrences all number
    0
    11
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Skin wound
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    2
    0
    Stab wound
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Contusion
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 184 (0.54%)
         occurrences all number
    1
    2
    Fall
         subjects affected / exposed
    1 / 59 (1.69%)
    2 / 184 (1.09%)
         occurrences all number
    1
    2
    Fibula fracture
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Head injury
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Inflammation of wound
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Limb injury
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Meniscus injury
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Patella fracture
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Skin laceration
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Atrial fibrillation
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Atrioventricular block second degree
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Bradycardia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Cardiac failure chronic
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Nodal rhythm
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Palpitations
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 184 (0.54%)
         occurrences all number
    1
    1
    Sinus bradycardia
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 184 (0.54%)
         occurrences all number
    1
    1
    Supraventricular extrasystoles
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Tachycardia
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Ventricular extrasystoles
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Nervous system disorders
    Carpal tunnel syndrome
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Balance disorder
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Cognitive disorder
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Dizziness
         subjects affected / exposed
    4 / 59 (6.78%)
    15 / 184 (8.15%)
         occurrences all number
    4
    17
    Extrapyramidal disorder
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Headache
         subjects affected / exposed
    2 / 59 (3.39%)
    11 / 184 (5.98%)
         occurrences all number
    2
    11
    Lethargy
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Migraine
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Neuralgia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Tremor
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Taste disorder
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    2
    Syncope
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    3
    Somnolence
         subjects affected / exposed
    1 / 59 (1.69%)
    3 / 184 (1.63%)
         occurrences all number
    1
    3
    Disturbance in attention
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 59 (0.00%)
    6 / 184 (3.26%)
         occurrences all number
    0
    8
    Pancytopenia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Lymph node pain
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    2 / 59 (3.39%)
    7 / 184 (3.80%)
         occurrences all number
    2
    8
    Tinnitus
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Eye disorders
    Diplopia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Eye irritation
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Dry eye
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Inguinal hernia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Abdominal discomfort
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Abdominal distension
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    3
    Abdominal pain
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Abdominal pain lower
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    4
    Constipation
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    3
    Diarrhoea
         subjects affected / exposed
    2 / 59 (3.39%)
    13 / 184 (7.07%)
         occurrences all number
    2
    17
    Dry mouth
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 184 (0.54%)
         occurrences all number
    1
    1
    Dyspepsia
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Epigastric discomfort
         subjects affected / exposed
    1 / 59 (1.69%)
    2 / 184 (1.09%)
         occurrences all number
    1
    2
    Eructation
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Flatulence
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Gastric dilatation
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Gastrointestinal sounds abnormal
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Impaired gastric emptying
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Stomatitis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Toothache
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 184 (0.54%)
         occurrences all number
    1
    1
    Vomiting
         subjects affected / exposed
    3 / 59 (5.08%)
    4 / 184 (2.17%)
         occurrences all number
    3
    4
    Nausea
         subjects affected / exposed
    5 / 59 (8.47%)
    7 / 184 (3.80%)
         occurrences all number
    5
    7
    Skin and subcutaneous tissue disorders
    Diabetic foot
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Dry skin
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Erythema
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Hyperhidrosis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 59 (0.00%)
    4 / 184 (2.17%)
         occurrences all number
    0
    4
    Rash macular
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Skin haemorrhage
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Skin ulcer
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 59 (1.69%)
    2 / 184 (1.09%)
         occurrences all number
    1
    2
    Renal impairment
         subjects affected / exposed
    1 / 59 (1.69%)
    4 / 184 (2.17%)
         occurrences all number
    1
    4
    Urethral stenosis
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Urine flow decreased
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Bladder pain
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    3
    Pollakiuria
         subjects affected / exposed
    2 / 59 (3.39%)
    1 / 184 (0.54%)
         occurrences all number
    2
    1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal discomfort
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Muscle spasms
         subjects affected / exposed
    3 / 59 (5.08%)
    2 / 184 (1.09%)
         occurrences all number
    3
    2
    Joint swelling
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Groin pain
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Gouty arthritis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Flank pain
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Calcification of muscle
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Bone pain
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Back pain
         subjects affected / exposed
    1 / 59 (1.69%)
    8 / 184 (4.35%)
         occurrences all number
    2
    8
    Arthralgia
         subjects affected / exposed
    1 / 59 (1.69%)
    3 / 184 (1.63%)
         occurrences all number
    1
    3
    Myalgia
         subjects affected / exposed
    2 / 59 (3.39%)
    1 / 184 (0.54%)
         occurrences all number
    3
    1
    Tendonitis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Tendon pain
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Rotator cuff syndrome
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Polyarthritis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Osteoarthritis
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    3
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Wound infection
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    2
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Cellulitis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Diverticulitis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Erysipelas
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Gangrene
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Herpes zoster
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Influenza
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 59 (1.69%)
    2 / 184 (1.09%)
         occurrences all number
    1
    2
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Subcutaneous abscess
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Tinea pedis
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Tooth abscess
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Tooth infection
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 59 (0.00%)
    2 / 184 (1.09%)
         occurrences all number
    0
    2
    Urinary tract infection
         subjects affected / exposed
    1 / 59 (1.69%)
    1 / 184 (0.54%)
         occurrences all number
    1
    1
    COVID-19
         subjects affected / exposed
    2 / 59 (3.39%)
    6 / 184 (3.26%)
         occurrences all number
    2
    6
    Metabolism and nutrition disorders
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Iron deficiency
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    3
    Decreased appetite
         subjects affected / exposed
    0 / 59 (0.00%)
    3 / 184 (1.63%)
         occurrences all number
    0
    3
    Food refusal
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Gout
         subjects affected / exposed
    1 / 59 (1.69%)
    0 / 184 (0.00%)
         occurrences all number
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Hyperkalaemia
         subjects affected / exposed
    1 / 59 (1.69%)
    2 / 184 (1.09%)
         occurrences all number
    1
    2
    Hypervolaemia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Hypocalcaemia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Hypoglycaemia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Hypokalaemia
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1
    Increased appetite
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    2
    Dehydration
         subjects affected / exposed
    0 / 59 (0.00%)
    1 / 184 (0.54%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    03 Sep 2020
    The following main modifications were introduced in amendment 1: • Exclusion criterion 2 was modified to exclude any significant heart diseases. • Exclusion criterion 10 was modified to exclude participants with diagnosis of COVID-19 within 3 months before signing the ICF. • A new exclusion criterion 12 was added to exclude Diabetes Mellitus type 1 patients from the study. • Exclusion criterion 19 was modified to exclude only participants in another study who have received at least 1 dose of study intervention. • A new exclusion criterion 25 was added to exclude participants with a known hypersensitivity to any ingredient of the study intervention. • Participants diagnosed with COVID-19 must be permanently withdrawn from the study intervention. • Primary analysis of UACR is to be based on UACR measured at Visit 4, Visit 5, and Visit 7.
    09 Jun 2021
    The major modification in amendment 2 was the addition of possibility of evaluation by closed strata.

    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
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    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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