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   44334   clinical trials with a EudraCT protocol, of which   7366   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, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Added to Metformin in Patients with Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin

    Summary
    EudraCT number
    		 2016-001800-49
    Trial protocol
    		 HU   SK  
    Global end of trial date
    22 Mar 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    03 Jul 2020
    First version publication date
    03 Jul 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    EFC14834
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02926950
    WHO universal trial number (UTN)
    		 U1111-1181-6145
    Sponsors
    Sponsor organisation name
    Lexicon Pharmaceuticals, Inc.
    Sponsor organisation address
    8800 Technology Forest Place, The Woodlands, United States, TX 77381
    Public contact
    Medical Affairs, Lexicon Pharmaceuticals, Inc., medical-information@lexpharma.com
    Scientific contact
    Medical Affairs, Lexicon Pharmaceuticals, Inc., medical-information@lexpharma.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
    22 Mar 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Mar 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the superiority of sotagliflozin versus placebo on hemoglobin A1c (HbA1c) reduction at week 26 in subjects with type 2 diabetes (T2D) who have inadequate glycemic control with metformin.
    Protection of trial subjects
    All study subjects were required to read and sign an informed consent form (ICF).
    Background therapy
    		 Subjects were taking metformin at a stable dosage >=1500 milligrams per day (mg/day) for at least 12 weeks before enrollment.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Nov 2016
    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
    Slovakia: 29
    Country: Number of subjects enrolled
    Hungary: 48
    Country: Number of subjects enrolled
    Canada: 52
    Country: Number of subjects enrolled
    United States: 389
    Worldwide total number of subjects
    518
    EEA total number of subjects
    77
    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)
    339
    From 65 to 84 years
    176
    85 years and over
    3

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects took part in the study at 87 investigative sites in Canada, Hungary, Slovakia and the United States from 11 November 2016 to 22 March 2019.

    Pre-assignment
    Screening details
    		 Subjects with a diagnosis of type 2 diabetes mellitus were enrolled in 1 of 2 treatment groups, Sotagliflozin 400 mg once daily (qd) + Metformin and Placebo + Metformin. Subjects were randomly assigned to the ratio of 1:1 to these reporting groups.

    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, Monitor, Data analyst, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo + Metformin
    Arm description
    		 Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and subjects continued the same treatment in the double-blind Extension Period for up to 53 weeks.
    Arm type
    		 Placebo comparator

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo was administered as 2 tablets (identical to the sotagliflozin tablet in appearance), once daily, before the first meal of the day.

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Metformin was administered orally as prescribed by the Principal Investigator.

    Arm title
    		 Sotagliflozin 400 mg + Metformin
    Arm description
    		 Following a 2-week run-in period, sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and subjects continued the same treatment in the double-blind Extension Period for up to 53 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Sotagliflozin
    Investigational medicinal product code
    Other name
    SAR439954
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day.

    Investigational medicinal product name
    Metformin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Metformin was administered orally as prescribed by the Principal Investigator.

    Number of subjects in period 1
    		Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Started
    259
    259
    Completed
    210
    211
    Not completed
    49
    48
         Adverse event
    4
    6
         At the patient’s own request
    21
    25
         Lost to follow-up
    7
    8
         Reason not Specified
    17
    9

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo + Metformin
    Reporting group description
    		 Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and subjects continued the same treatment in the double-blind Extension Period for up to 53 weeks.

    Reporting group title
    Sotagliflozin 400 mg + Metformin
    Reporting group description
    		 Following a 2-week run-in period, sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and subjects continued the same treatment in the double-blind Extension Period for up to 53 weeks.

    Reporting group values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin Total
    Number of subjects
    		 259 259 518
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 59.9 ( 9.4 ) 60.0 ( 10.1 ) -
    Gender categorical
    Units: Subjects
        Female
    		 113 117 230
        Male
    		 146 142 288
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 1 2 3
        Asian
    		 19 6 25
        Black or African American
    		 40 28 68
        Native Hawaiian or other Pacific Islander
    		 1 0 1
        White
    		 197 223 420
        Unknown
    		 1 0 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 106 117 223
        Not Hispanic or Latino
    		 153 140 293
        Not reported
    		 0 2 2
    Hemoglobin A1c (HbA1c)
    Units: percentage of HbA1c
        arithmetic mean (standard deviation)
    		 8.19 ( 0.82 ) 8.20 ( 0.78 ) -
    Systolic Blood Pressure (SBP)
    Units: Millimetre of Mercury (mmHg)
        arithmetic mean (standard deviation)
    		 133.80 ( 13.95 ) 134.06 ( 13.95 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo + Metformin
    Reporting group description
    		 Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and subjects continued the same treatment in the double-blind Extension Period for up to 53 weeks.

    Reporting group title
    Sotagliflozin 400 mg + Metformin
    Reporting group description
    		 Following a 2-week run-in period, sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and subjects continued the same treatment in the double-blind Extension Period for up to 53 weeks.

    Primary: Change from Baseline in Hemoglobin A1c (HbA1c) at Week 26

    		 Close Top of page
    End point title
    		 Change from Baseline in Hemoglobin A1c (HbA1c) at Week 26
    End point description
    Intent-to-treat (ITT) population included all randomised subjects. Missing data was imputed using the retrieved dropouts & washout imputation method. An analysis of covariance (ANCOVA) model was used for the analysis.
    End point type
    Primary
    End point timeframe
    Baseline and Week 26
    End point values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Number of subjects analysed
    259
    259
    Units: percentage of HbA1c
        least squares mean (standard error)
    -0.29 ( 0.079 )
    -0.77 ( 0.077 )
    Statistical analysis title
    		 Sotagliflozin Vs Placebo
    Statistical analysis description
    The change from baseline to Week 26 is analysed using an ANCOVA model with treatment groups, randomisation strata of HbA1c (≤8.0, >8.0%) at screening, randomisation strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.
    Comparison groups
    Placebo + Metformin v Sotagliflozin 400 mg + Metformin
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in Least Square (LS) Means
    Point estimate
    -0.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.64
         upper limit
    		 -0.309
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.084

    Secondary: Change from Baseline in 2-hour Postprandial Glucose (PPG) following a Mixed Meal at Week 26

    		 Close Top of page
    End point title
    		 Change from Baseline in 2-hour Postprandial Glucose (PPG) following a Mixed Meal at Week 26
    End point description
    ITT population included all randomised subjects. Missing data are imputed using control-based copy reference multiple imputation method. An ANCOVA model was used for the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 26
    End point values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Number of subjects analysed
    259
    259
    Units: millimole per litre (mmol/L)
        least squares mean (standard error)
    -0.930 ( 0.2353 )
    -2.502 ( 0.2292 )
    Statistical analysis title
    		 Sotagliflozin Vs Placebo
    Statistical analysis description
    The change from baseline to Week 26 was analysed using an ANCOVA model with treatment groups, randomisation strata of HbA1c (≤8.0, >8.0%) at screening, randomisation strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and country as fixed effects, and baseline 2-hour postprandial glucose as a covariate.
    Comparison groups
    Placebo + Metformin v Sotagliflozin 400 mg + Metformin
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    -1.572
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.0538
         upper limit
    		 -1.0909
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2457

    Secondary: Change from Baseline in Fasting Plasma Glucose (FPG) at Week 26

    		 Close Top of page
    End point title
    		 Change from Baseline in Fasting Plasma Glucose (FPG) at Week 26
    End point description
    ITT population included all randomised subjects. Missing data was imputed using retrieved dropouts and washout imputation method. An ANCOVA model was used for the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 26
    End point values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Number of subjects analysed
    259
    259
    Units: mmol/L
        least squares mean (standard error)
    -0.550 ( 0.1864 )
    -1.310 ( 0.2089 )
    Statistical analysis title
    		 Sotagliflozin Vs Placebo
    Statistical analysis description
    The change from baseline to Week 26 is analysed using an ANCOVA model with treatment groups, randomisation strata of HbA1c (≤8.0, >8.0%) at screening, randomisation strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline fasting plasma glucose as a covariate.
    Comparison groups
    Placebo + Metformin v Sotagliflozin 400 mg + Metformin
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0007
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    -0.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2006
         upper limit
    		 -0.3198
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.2247

    Secondary: Change from Baseline in Body Weight at Week 26

    		 Close Top of page
    End point title
    		 Change from Baseline in Body Weight at Week 26
    End point description
    ITT population included all randomised subjects. Missing data was imputed using retrieved dropouts and washout imputation method. An ANCOVA model was used for the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 26
    End point values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Number of subjects analysed
    259
    259
    Units: kilogram (kg)
        least squares mean (standard error)
    -0.69 ( 0.310 )
    -2.56 ( 0.331 )
    Statistical analysis title
    		 Sotagliflozin Vs Placebo
    Statistical analysis description
    The change from baseline to Week 26 is analysed using an ANCOVA model with treatment groups, randomisation strata of HbA1c (≤8.0, >8.0%) at screening, randomisation strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and country as fixed effects, and baseline weight as a covariate.
    Comparison groups
    Placebo + Metformin v Sotagliflozin 400 mg + Metformin
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    -1.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.591
         upper limit
    		 -1.144
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.369

    Secondary: Change from Baseline in SBP at Week 12 in Subjects with Baseline SBP ≥130 mmHg

    		 Close Top of page
    End point title
    		 Change from Baseline in SBP at Week 12 in Subjects with Baseline SBP ≥130 mmHg
    End point description
    Analysis was performed on ITT population in subjects with baseline SBP ≥130 mmHg. Missing data was imputed using control-based copy reference multiple imputation method. An ANCOVA model was used for the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 26
    End point values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Number of subjects analysed
    129
    137
    Units: millimetre of mercury (mmHg)
        least squares mean (standard error)
    -6.92 ( 1.233 )
    -10.21 ( 1.270 )
    Statistical analysis title
    		 Sotagliflozin Vs Placebo
    Statistical analysis description
    The change from baseline to Week 12 is analysed using an ANCOVA model with treatment groups, randomisation strata of HbA1c (≤ 8.0, >8.0%) at screening, and country as fixed effects, and baseline SBP as a covariate.
    Comparison groups
    Placebo + Metformin v Sotagliflozin 400 mg + Metformin
    Number of subjects included in analysis
    266
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0209
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    -3.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.07
         upper limit
    		 -0.497
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.422

    Secondary: Change from Baseline in SBP at Week 12 for all Subjects

    		 Close Top of page
    End point title
    		 Change from Baseline in SBP at Week 12 for all Subjects
    End point description
    ITT population included all randomised subjects. Missing data was imputed using control-based copy reference multiple imputation method. An ANCOVA model was used for the analysis.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Number of subjects analysed
    259
    259
    Units: mmHg
        least squares mean (standard error)
    -1.87 ( 0.949 )
    -5.41 ( 0.950 )
    Statistical analysis title
    		 Sotagliflozin Vs Placebo
    Statistical analysis description
    The change from baseline to Week 12 is analysed using an ANCOVA model with treatment groups, randomisation strata of HbA1c (≤ 8.0, >8.0%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline SBP as a covariate.
    Comparison groups
    Placebo + Metformin v Sotagliflozin 400 mg + Metformin
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0004
    Method
    		 ANCOVA
    Parameter type
    		 Difference in LS Means
    Point estimate
    -3.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.479
         upper limit
    		 -1.592
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.992

    Secondary: Percentage of Subjects with HbA1c <6.5% at Week 26

    		 Close Top of page
    End point title
    		 Percentage of Subjects with HbA1c <6.5% at Week 26
    End point description
    ITT population included all randomised subjects.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Number of subjects analysed
    259
    259
    Units: percentage of subjects
        number (not applicable)
    5.4
    10.8
    Statistical analysis title
    		 Sotagliflozin Vs Placebo
    Statistical analysis description
    Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomisation strata of HbA1c (≤8.0, >8.0%) at screening, randomisation strata of mean SBP (<130, ≥130 mmHg) at screening. Missing data at Week 26 were assigned a status of nonresponder in the analysis.
    Comparison groups
    Placebo + Metformin v Sotagliflozin 400 mg + Metformin
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0238
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Percentage Difference
    Point estimate
    5.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.75
         upper limit
    		 10.06

    Secondary: Percentage of Subjects with HbA1c <7.0% at Week 26

    		 Close Top of page
    End point title
    		 Percentage of Subjects with HbA1c <7.0% at Week 26
    End point description
    ITT population included all randomised subjects.
    End point type
    Secondary
    End point timeframe
    Week 26
    End point values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Number of subjects analysed
    259
    259
    Units: percentage of subjects
        number (not applicable)
    15.8
    29.7
    Statistical analysis title
    		 Sotagliflozin Vs Placebo
    Statistical analysis description
    Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomisation strata of HbA1c (≤8.0, >8.0%) at screening, randomisation strata of mean SBP (<130, ≥130 mmHg) at screening. Missing data at Week 26 were assigned a status of nonresponder in the analysis.
    Comparison groups
    Sotagliflozin 400 mg + Metformin v Placebo + Metformin
    Number of subjects included in analysis
    518
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Percentage Difference
    Point estimate
    13.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.91
         upper limit
    		 20.89

    Other pre-specified: Percentage of Subjects with Hypoglycemic Events

    		 Close Top of page
    End point title
    		 Percentage of Subjects with Hypoglycemic Events
    End point description
    Percentage of subjects with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia [typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L)]; Severe [an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions] or documented symptomatic hypoglycemia [typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL]. Subjects may be reported in more than one category. Safety population was defined as all randomised subjects who had received at least 1 dose of the double-blind investigational medicinal product
    End point type
    Other pre-specified
    End point timeframe
    Up to 79 weeks in the treatment period
    End point values
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Number of subjects analysed
    259
    259
    Units: percentage of subjects
    number (not applicable)
        Any hypoglycemia
    11.6
    6.6
        Documented symptomatic hypoglycemia
    6.2
    3.1
        Severe or documented symptomatic hypoglycemia
    6.2
    3.1
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    First dose of study drug to last dose of study drug (up to 79 weeks) + 4 weeks
    Adverse event reporting additional description
    Safety population was defined as all randomised subjects who had received at least 1 dose of the double-blind investigational medicinal product (IMP). Hypoglycemia was captured and handled separately from other adverse events and is reported in the endpoint section.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Placebo + Metformin
    Reporting group description
    		 Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and subjects continued the same treatment in the double-blind Extension Period for up to 53 weeks.

    Reporting group title
    Sotagliflozin 400 mg + Metformin
    Reporting group description
    		 Following a 2-week run-in period, sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and subjects continued the same treatment in the double-blind Extension Period for up to 53 weeks.

    Serious adverse events
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    23 / 259 (8.88%)
    19 / 259 (7.34%)
         number of deaths (all causes)
    1
    3
         number of deaths resulting from adverse events
    0
    2
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Biliary neoplasm
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Intraductal papillary mucinous neoplasm
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Invasive breast carcinoma
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal oncocytoma
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Salivary gland cancer recurrent
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest discomfort
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 259 (0.00%)
    2 / 259 (0.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical polyp
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colpocele
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Acetabulum fracture
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    0 / 259 (0.00%)
    2 / 259 (0.77%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiopulmonary failure
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Coronary artery disease
         subjects affected / exposed
    1 / 259 (0.39%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 259 (0.77%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sinus tachycardia
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Carotid artery stenosis
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebellar stroke
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral artery thrombosis
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 259 (0.39%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhagic cerebral infarction
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial venous sinus thrombosis
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolic encephalopathy
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Pancreatitis acute
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (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
    Neurodermatitis
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Calculus urethral
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal cyst
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    2 / 259 (0.77%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 259 (0.00%)
    2 / 259 (0.77%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 259 (0.39%)
    3 / 259 (1.16%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo + Metformin Sotagliflozin 400 mg + Metformin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    109 / 259 (42.08%)
    85 / 259 (32.82%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    13 / 259 (5.02%)
    3 / 259 (1.16%)
         occurrences all number
    13
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    15 / 259 (5.79%)
    6 / 259 (2.32%)
         occurrences all number
    17
    7
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    11 / 259 (4.25%)
    22 / 259 (8.49%)
         occurrences all number
    12
    25
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    19 / 259 (7.34%)
    8 / 259 (3.09%)
         occurrences all number
    21
    9
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    17 / 259 (6.56%)
    5 / 259 (1.93%)
         occurrences all number
    20
    6
    Nasopharyngitis
         subjects affected / exposed
    17 / 259 (6.56%)
    14 / 259 (5.41%)
         occurrences all number
    20
    20
    Upper respiratory tract infection
         subjects affected / exposed
    20 / 259 (7.72%)
    20 / 259 (7.72%)
         occurrences all number
    23
    22
    Urinary tract infection
         subjects affected / exposed
    15 / 259 (5.79%)
    16 / 259 (6.18%)
         occurrences all number
    18
    22
    Metabolism and nutrition disorders
    Vitamin D deficiency
         subjects affected / exposed
    19 / 259 (7.34%)
    14 / 259 (5.41%)
         occurrences all number
    19
    14

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    24 Apr 2017
    Amendment 1: 1. Addition of SBP endpoints at Week 26 and Week 79, addition of HbA1c, fasting plasma glucose and body weight endpoints at Week 79. 2. Addition of adverse event leading to an amputation as a new event of special interest. 3. Drug-induced liver injury removed as an event of special interest. 4. Addition of urine cultures in the event of abnormal urinalysis findings. 5. Addition of a Steering Committee to the study. 6. Addition of exclusion criteria at randomisation.
    19 Dec 2017
    Amendment 2: 1. Change to guidance on contraceptive methods. 2. Change to temporary IMP discontinuation. 3. Change to the general guidelines for reporting of adverse events (AEs). 4. Remove urgent coronary revascularizations from the events subject to the Clinical Endpoint Committees (CECs) review. 5. Addition of a new section to describe the independent safety assessments for drug-induced liver injuries (DILI) and amputation. 6. Changes to the observation period for safety endpoints. 7. Change to code breaking related to pharmacokinetic (PK) laboratory. 8. Change to the definition of one Event of Special Interest (EOSI), “volume depletion”. 9. Change to definition of baseline for estimated glomerular filtration rate (eGFR). 10. Change to urine laboratory test. 11. Change in the order of secondary objectives and endpoints for the study. 11. Other minor changes for corrections of inconsistency, editorial changes, or administration clarification.

    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-Sun May 04 02:13:48 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA