Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A randomized, double-blind, parallel-group, 2-treatment multiple dose study to assess the intestinal, metabolic and cardiovascular effects of an 8 weeks treatment with sotagliflozin once daily (QD) as compared with empagliflozin QD in type 2 diabetes mellitus (T2DM) subjects with mild to moderate hypertension.

    Summary
    EudraCT number
    		 2017-002309-36
    Trial protocol
    		 DE  
    Global end of trial date
    18 Apr 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 May 2020
    First version publication date
    02 May 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    PDY15010
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03462069
    WHO universal trial number (UTN)
    		 U1111-1186-2962
    Sponsors
    Sponsor organisation name
    Sanofi aventis recherche & développement
    Sponsor organisation address
    1 Avenue Pierre Brossolette, Chilly Mazarin, France, 91380
    Public contact
    Trial Transparency Team, Sanofi-aventis Recherche & Développement, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi-aventis Recherche & Développement, Contact-US@sanofi.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
    05 Aug 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Apr 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the metabolic and gastrointestinal pharmacodynamic (PD) effects of an 8 weeks treatment with 400 milligram (mg) sotagliflozin once daily (QD) to an 8 weeks treatment to empagliflozin QD in mild or moderate hypertensive type 2 diabetes mellitus (T2DM) subjects on a stable treatment regimen with metformin and an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) under standardised diet conditions.
    Protection of trial subjects
    Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject was participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    		 Stable treatment with metformin and ACE inhibitor or ARB was used as background therapy.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 Mar 2018
    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
    Germany: 41
    Worldwide total number of subjects
    41
    EEA total number of subjects
    41
    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)
    24
    From 65 to 84 years
    17
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was conducted at a single center in Germany. A total of 137 subjects were screened between 06-March-2018 and 16 February 2019. Of which, 96 subjects were screen failures due to inclusion/exclusion criteria not met.

    Pre-assignment
    Screening details
    		 A total of 41 subjects were randomized and treated in the study.

    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
    		 Sotagliflozin 400 mg
    Arm description
    		 Subjects received sotagliflozin 400 mg tablet QD along with a placebo (for empagliflozin) prior to the first meal of the day for 56 days (Days 1 to 56).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sotagliflozin
    Investigational medicinal product code
    SAR439954
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Sotagliflozin 2*200 mg tablets were administered orally with 240 millilitre (mL) of water once a day prior to the first meal of the day.

    Arm title
    		 Empagliflozin 25 mg
    Arm description
    		 Subjects received one empagliflozin 25 mg capsule along with 2 placebo (for sotagliflozin) prior to the first meal of the day for 56 days (Days 1 to 56).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Empagliflozin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Empagliflozin 25 mg capsule was administered orally with 240 mL of water once a day prior to the first meal of the day.

    Number of subjects in period 1
    		Sotagliflozin 400 mg Empagliflozin 25 mg
    Started
    20
    21
    Completed
    19
    20
    Not completed
    1
    1
         Other than specified
    -
    1
         Poor compliance to protocol
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Sotagliflozin 400 mg
    Reporting group description
    		 Subjects received sotagliflozin 400 mg tablet QD along with a placebo (for empagliflozin) prior to the first meal of the day for 56 days (Days 1 to 56).

    Reporting group title
    Empagliflozin 25 mg
    Reporting group description
    		 Subjects received one empagliflozin 25 mg capsule along with 2 placebo (for sotagliflozin) prior to the first meal of the day for 56 days (Days 1 to 56).

    Reporting group values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg Total
    Number of subjects
    		 20 21 41
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.0 ( 8.4 ) 61.3 ( 8.1 ) -
    Gender categorical
    Units: Subjects
        Female
    		 4 4 8
        Male
    		 16 17 33

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Sotagliflozin 400 mg
    Reporting group description
    		 Subjects received sotagliflozin 400 mg tablet QD along with a placebo (for empagliflozin) prior to the first meal of the day for 56 days (Days 1 to 56).

    Reporting group title
    Empagliflozin 25 mg
    Reporting group description
    		 Subjects received one empagliflozin 25 mg capsule along with 2 placebo (for sotagliflozin) prior to the first meal of the day for 56 days (Days 1 to 56).

    Primary: Mean Change From Baseline in 24-Hour Urinary Glucose Excretion (UGE) to Week 8

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in 24-Hour Urinary Glucose Excretion (UGE) to Week 8
    End point description
    The 24-hour UGE was calculated from the 4-fractioned 24-hour urine collection, separately on Day -1 (Baseline) and on Week 8 (Day 56). Analysis was performed on PD population which included all subjects with no major or critical deviations related to investigational medicinal products (IMP) and/or PD procedures and measurements, for whom the PD data were considered sufficient and interpretable. Here, ‘number of subject analysed’ = subjects evaluable for this end-point.
    End point type
    Primary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    17
    18
    Units: millimoles (mmoL)
        least squares mean (standard error)
    130.941 ( 13.587 )
    158.424 ( 13.196 )
    Statistical analysis title
    		 Sotagliflozin versus Empagliflozin
    Statistical analysis description
    Analysis was performed using Linear fixed effects model with treatment group (Sotagliflozin 400 mg, Empagliflozin 25 mg) as fixed effects and baseline 24-hour UGE value as covariate.
    Comparison groups
    Sotagliflozin 400 mg v Empagliflozin 25 mg
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1604
    Method
    		 Linear fixed effects model
    Parameter type
    		 Least Square (LS) Mean Difference
    Point estimate
    27.483
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.474
         upper limit
    		 66.441
    Variability estimate
    Standard error of the mean
    Dispersion value
    19.126

    Primary: Mean Change From Baseline in 24-Hour Urine Creatinine to Week 8

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in 24-Hour Urine Creatinine to Week 8
    End point description
    The 24-hour urine creatinine concentration was calculated from the 4-fractioned 24-hour urine collection divided by the total urine volume collected within 24 hours, separately on Day -1 (Baseline) and Week 8 (Day 56). Analysis was performed on PD population. Here, ‘number of subject analysed’ = subjects evaluable for this end-point.
    End point type
    Primary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    18
    19
    Units: gram per millilitre (g/mL)
        least squares mean (standard error)
    -0.205 ( 0.052 )
    -0.358 ( 0.051 )
    Statistical analysis title
    		 Sotagliflozin versus Empagliflozin
    Statistical analysis description
    Analysis was performed using Linear fixed effects model with treatment group (Sotagliflozin 400 mg, Empagliflozin 25 mg) as fixed effects and baseline 24-hour urine creatinine concentration value as covariate.
    Comparison groups
    Sotagliflozin 400 mg v Empagliflozin 25 mg
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0433
    Method
    		 Linear fixed effects model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.153
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.302
         upper limit
    		 -0.005
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.073

    Primary: Mean Change From Baseline in 48-Hour Fecal Firmicutes/Bacteroidetes Ratio to Week 8

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in 48-Hour Fecal Firmicutes/Bacteroidetes Ratio to Week 8
    End point description
    The 48-hour ratio of the firmicutes over bacteroidetes classes of bacteria was calculated from Firmicutes/bacteroidetes ratios and weight of stool portion measured separately on Day -2 and -1 (Baseline) and on Week 8 (Day 55 and 56). Analysis was performed on PD population. Here, ‘number of subject analysed’ = subjects evaluable for this end-point.
    End point type
    Primary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    18
    15
    Units: ratio
        least squares mean (standard error)
    -74.11 ( 36.95 )
    -60.15 ( 40.51 )
    Statistical analysis title
    		 Sotagliflozin versus Empagliflozin
    Statistical analysis description
    Analysis was performed using Linear fixed effects model with treatment group (Sotagliflozin 400 mg, Empagliflozin 25 mg) as fixed effects and baseline 48-hour Firmicutes/bacteroidetes ratio value as covariate.
    Comparison groups
    Sotagliflozin 400 mg v Empagliflozin 25 mg
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.8017
    Method
    		 Linear fixed effects model
    Parameter type
    		 LS Mean Difference
    Point estimate
    13.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -98.55
         upper limit
    		 126.46
    Variability estimate
    Standard error of the mean
    Dispersion value
    55.09

    Primary: Mean Change From Baseline in Incremental AUC0:00-14:00 Hour of Plasma Glucose to Week 8

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Incremental AUC0:00-14:00 Hour of Plasma Glucose to Week 8
    End point description
    The incremental area under the plasma glucose concentration time curve over 14 hours (AUC0-14h) after standardized meals was calculated using the linear trapezoidal rule by correcting the post meal values for the glucose measured pre-meal. Baseline was defined as Day-1 and Week 8 was defined as Day 56. Analysis was performed on PD population. Here, ‘number of subject analysed’ = subjects evaluable for this end-point.
    End point type
    Primary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    17
    18
    Units: hour*milligram per decilitre (hr*mg/dL)
        least squares mean (standard error)
    -103.05 ( 38.55 )
    -73.66 ( 37.46 )
    Statistical analysis title
    		 Sotagliflozin versus Empagliflozin
    Statistical analysis description
    Analysis was performed using Linear fixed effects model with treatment group (Sotagliflozin 400 mg, Empagliflozin 25 mg) as fixed effects and baseline Glucose (plasma) incremental AUC0:00-14:00-hour value as covariate.
    Comparison groups
    Sotagliflozin 400 mg v Empagliflozin 25 mg
    Number of subjects included in analysis
    35
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.5889
    Method
    		 Linear fixed effects model
    Parameter type
    		 LS Mean Difference
    Point estimate
    29.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -80.27
         upper limit
    		 139.05
    Variability estimate
    Standard error of the mean
    Dispersion value
    53.83

    Primary: Mean Change From Baseline in Incremental AUC0:00-14:00 Hour of C-peptide to Week 8

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Incremental AUC0:00-14:00 Hour of C-peptide to Week 8
    End point description
    The incremental area under the C-peptide concentration time curve over 14 hours (AUC0-14h) after standardized meals was calculated using the linear trapezoidal rule by correcting the post meal values for the C-peptide measured pre-meal. Baseline was defined as Day-1 and Week 8 was defined as Day 56. Analysis was performed on PD population. Here, ‘number of subject analysed’ = subjects evaluable for this end-point.
    End point type
    Primary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    18
    18
    Units: hour*nanomoles per liter (h*nmol/L)
        least squares mean (standard error)
    -2.42 ( 0.73 )
    -1.91 ( 0.73 )
    Statistical analysis title
    		 Sotagliflozin versus Empagliflozin
    Statistical analysis description
    Analysis was performed using Linear fixed effects model with treatment group (Sotagliflozin 400 mg, Empagliflozin 25 mg) as fixed effects and baseline C-peptide (plasma) incremental AUC0:00-14:00 hour value as covariate.
    Comparison groups
    Sotagliflozin 400 mg v Empagliflozin 25 mg
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.6297
    Method
    		 Linear fixed effects model
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.61
         upper limit
    		 2.62
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.04

    Primary: Mean Change From Baseline in Incremental AUC0:00-14:00 Hour of Active GLP-1 to Week 8

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Incremental AUC0:00-14:00 Hour of Active GLP-1 to Week 8
    End point description
    The incremental area under the Active GLP-1 concentration time curve over 14 hours (AUC0-14h) after standardized meals was calculated using the linear trapezoidal rule by correcting the post meal values for the Active GLP-1 measured pre-meal. Baseline was defined as Day-1 and Week 8 was defined as Day 56. Analysis was performed on PD population. Here, ‘number of subject analysed’ = subjects evaluable for this end-point.
    End point type
    Primary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    18
    18
    Units: hour*nanogram per litre (h*ng/L)
        least squares mean (standard error)
    22.51 ( 9.47 )
    -8.41 ( 9.47 )
    Statistical analysis title
    		 Sotagliflozin versus Empagliflozin
    Statistical analysis description
    Analysis was performed using Linear fixed effects model with treatment group (Sotagliflozin 400 mg, Empagliflozin 25 mg) as fixed effects and baseline Active GLP1 (plasma) incremental AUC0:00-14:00 hour value as covariate.
    Comparison groups
    Sotagliflozin 400 mg v Empagliflozin 25 mg
    Number of subjects included in analysis
    36
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0273
    Method
    		 Linear fixed effects model
    Parameter type
    		 LS Mean Difference
    Point estimate
    -30.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -58.16
         upper limit
    		 -3.68
    Variability estimate
    Standard error of the mean
    Dispersion value
    13.39

    Secondary: Mean Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 8

    		 Close Top of page
    End point title
    		 Mean Change From Baseline in Blood Pressure (Systolic and Diastolic) to Week 8
    End point description
    Average 24-hour mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) was measured as per ambulatory blood pressure monitoring (ABPM) at baseline (from Day -3 to Day 1) and at Week 8 (from Day 54 to Day 57). Analysis was performed on PD population. Here, ‘number of subjects analysed’ = subjects evaluable for this end-point.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    14
    17
    Units: millimetres of mercury (mmHg)
    least squares mean (standard error)
        SBP
    -4.6 ( 1.5 )
    -7.9 ( 1.4 )
        DBP
    -2.3 ( 0.9 )
    -3.7 ( 0.9 )
    No statistical analyses for this end point

    Secondary: Echocardiography: Change From Baseline in Left Ventricular End-Diastolic Diameter (LVEDD) and Left Ventricular Ejection Fraction (LVEF) to Week 8

    		 Close Top of page
    End point title
    		 Echocardiography: Change From Baseline in Left Ventricular End-Diastolic Diameter (LVEDD) and Left Ventricular Ejection Fraction (LVEF) to Week 8
    End point description
    Baseline was defined as Day -3 and Week 8 was defined as Day 54. Analysis was performed on PD population. Here, ‘n’=subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    19
    20
    Units: unit in categories
    arithmetic mean (standard deviation)
        LVEDD (mm) (n=19,20)
    -0.9 ( 2.7 )
    -0.9 ( 3.7 )
        LVEF (percent) (n=18,19)
    5.1 ( 7.9 )
    3.0 ( 10.9 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Aortic augmentation index at 75 Beats per Minute (bpm) (%) to Week 8

    		 Close Top of page
    End point title
    		 Change From Baseline in Aortic augmentation index at 75 Beats per Minute (bpm) (%) to Week 8
    End point description
    Pulse wave velocity was measured through aortic augmentation index at 75 bpm. Aortic augmentation index is the ratio of the augmentation pressure to the central pulse pressure, expressed as a percentage. Pulse wave velocity was assessed at baseline (Day -2) and Week 8 (Day 55), and device used was Sphygmocor XCEL (or equivalent device). Analysis was performed on PD population.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    19
    20
    Units: percentage
        least squares mean (standard error)
    -0.05 ( 2.19 )
    -1.03 ( 2.13 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Plasma Volume to Week 8

    		 Close Top of page
    End point title
    		 Change From Baseline in Plasma Volume to Week 8
    End point description
    The plasma volume was estimated using the indocyanine-green (ICG) dilution method. Plasma volume was calculated for each subject on Day -3 (Baseline) and on Day 54 (on treatment). Analysis was performed on PD population. Here, ‘subjects analysed’ = subjects evaluable for this end-point.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    16
    19
    Units: Litre (L)
        least squares mean (standard error)
    0.116 ( 0.201 )
    -0.228 ( 0.185 )
    No statistical analyses for this end point

    Secondary: Continuous Glucose Monitoring (CGM): Mean Change From Baseline in Average Diurnal Glucose Exposure to Week 8

    		 Close Top of page
    End point title
    		 Continuous Glucose Monitoring (CGM): Mean Change From Baseline in Average Diurnal Glucose Exposure to Week 8
    End point description
    Baseline was defined as Day -4, Day -3 and Day -2 and Week 8 as Day 53, Day 54 and Day 55. Analysis was performed on PD population. Here, ‘number of subjects analysed’ = subjects evaluable for this end-point.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 8
    End point values
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Number of subjects analysed
    15
    17
    Units: milligram per decilitre (mg/dL)
        least squares mean (standard error)
    -21.254 ( 4.027 )
    -28.697 ( 3.780 )
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All Adverse Events (AEs) were collected from time of first dose of study drug up to end of study (Day 70) regardless of seriousness or relationship to investigational product.
    Adverse event reporting additional description
    Reported AEs are treatment emergent AEs (TEAEs) that developed/worsened during ‘on-treatment period’ (from first IMP administration up to 10 days (1 day for hypoglycemia) after the last administration of IMP). Analysis was performed on safety population that included all subjects exposed to IMP (regardless of the amount of treatment administered).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Sotagliflozin 400 mg
    Reporting group description
    		 Subjects received sotagliflozin 400 mg tablet QD along with a placebo (for empagliflozin) prior to the first meal of the day for 56 days (Days 1 to 56).

    Reporting group title
    Empagliflozin 25 mg
    Reporting group description
    		 Subjects received one empagliflozin 25 mg capsule along with 2 placebo (for sotagliflozin) prior to the first meal of the day for 56 days (Days 1 to 56).

    Serious adverse events
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 20 (0.00%)
    0 / 21 (0.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Sotagliflozin 400 mg Empagliflozin 25 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 20 (80.00%)
    13 / 21 (61.90%)
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Catheter Site Haematoma
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Fatigue
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    Infusion Site Hypersensitivity
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Medical Device Site Haematoma
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Erectile Dysfunction
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Pruritus Genital
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Investigations
    Urine Viscosity Abnormal
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Accidental Overdose
         subjects affected / exposed
    3 / 20 (15.00%)
    1 / 21 (4.76%)
         occurrences all number
    3
    1
    Contusion
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Muscle Strain
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Extrasystoles
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Dizziness Postural
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    Headache
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    Paraesthesia
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    Sciatica
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal Distension
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Abdominal Pain
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Dry Mouth
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    Dyspepsia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Faeces Discoloured
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Haemorrhoids
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Hyperhidrosis
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Skin Hypopigmentation
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Micturition Urgency
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Pollakiuria
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    Polyuria
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Urge Incontinence
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Muscle Spasms
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal Pain
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Neck Pain
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Pain In Extremity
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Genital Infection Fungal
         subjects affected / exposed
    2 / 20 (10.00%)
    0 / 21 (0.00%)
         occurrences all number
    4
    0
    Nasopharyngitis
         subjects affected / exposed
    4 / 20 (20.00%)
    2 / 21 (9.52%)
         occurrences all number
    4
    2
    Sinusitis
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Tinea Infection
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1
    Urinary Tract Infection
         subjects affected / exposed
    1 / 20 (5.00%)
    0 / 21 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    1 / 20 (5.00%)
    1 / 21 (4.76%)
         occurrences all number
    1
    1
    Hypoglycaemia
         subjects affected / exposed
    0 / 20 (0.00%)
    1 / 21 (4.76%)
         occurrences all number
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Jan 2018
    The following changes were made: - justified why no formal sample size was performed; clarified the reasons for withdrawal of a subject upon the Principal Investigator's (PI’s) decision or at the specific request of the sponsor; modified the age range for inclusion from 18 to 75 years to 18 to 74 years of age; added an additional exclusion criterion to specify known hypersensitivity to sotagliflozin, empagliflozin, or any excipient of these drug products; justified the initiation of empagliflozin dosing at the highest approved dose level of 25 mg QD without prior up-titration from 10 mg QD. Additional references with clinical safety data of this dosing regimen with empagliflozin were added; clarified the safety analyses of hypoglycemic events; modified inclusion criterion to exclude explicitly individuals under institutionalization due to regulatory or juridical order; exclusion criterion was clarified regarding exclusion of subjects depending on study site, the PI, or the Sponsor; specified the 1996 version of the Declaration of Helsinki; enforced the wording for the requirement of signing the Inform Consent Form prior to a subject’s participation in the clinical trial.
    11 Apr 2018
    The following changes were made:- inclusion criteria for glycosylated hemoglobin A1C (HbA1c) and body weight ranges were modified to better harmonize the study population with the Phase 3 program of sotagliflozin in T2DM subjects. The range of HbA1c was modified to 6.5%-11%. Body weight was modified to at least 50 kg, if male, and at least 40 kg, if female; in the main selection criteria, it was clarified that SBP was to be in the range of 140-179 mm Hg. The DBP range was removed in the main selection criteria; the safety parameter, serum β-hydroxybutyrate, was assessed at screening, Day -5, the first outpatient visit, Day 52, and end-of-study visit. Additionally, this parameter was part of the PD lab on Day -1 and Day 56; the amount of blood sampling was slightly reduced for several parameters; hematology parameters for cardiovascular panel were analyzed from safety hematology tube; amylase and lipase were added to the parameters assessed in laboratory tests (biochemistry).
    30 Aug 2018
    The following changes were made:- a drug washout/switch period was added for eligible subjects who were on beta-blockers and/or thiazides to switch to ACE inhibitor or ARB to be able to participate in the study. Also, the upper limit of body mass index was changed from 35 kilogram per meter square (kg/m^2) to 38 kg/m^2; it was clarified that subjects on thiazides had to switch to ACE inhibitors or ARB to be eligible for study participation; it was clarified that, if possible, fecal calprotectin and intestinal alkaline phosphatase and GIP plasma profiles would be investigated; the total study duration with and without the drug washout/switch period was clarified; a new inclusion criterion was added to allow eligible subjects who were on beta-blockers and/or thiazides to participate in the study after switching to ACE inhibitor or ARB.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 00:44:01 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA