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SOTA-CKD4: A Study to Evaluate Safety and Effects of Sotagliflozin 400 and 200 mg on Glucose Control in Participants With Type 2 Diabetes, Severe Impairment of Kidney Function and Inadequate Blood Sugar Control

Sponsor
Lexicon Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03242018
Collaborator
Sanofi (Industry)
277
Enrollment
106
Locations
3
Arms
27.8
Actual Duration (Months)
2.6
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate the superiority of sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1c (HbA1c) reduction at Week 26 in participants with Type 2 diabetes who have inadequate glycemic control and severe renal impairment

Secondary Objectives:

  • To assess the effects of sotagliflozin 200 mg versus placebo based on change from baseline in HbA1c

  • To assess the effects of sotagloflozin 400 mg and 200 mg versus placebo

  • To evaluate the safety of sotagliflozin 400 mg and 200 mg versus placebo

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The study duration is up to 60 weeks including 4 weeks prior to randomization, 52 weeks of randomized treatment and a visit 4 weeks after completion of the randomized treatment period.

Study Design

Study Type:
Interventional
Actual Enrollment :
277 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-blind, Placebo-controlled, 3-arm, Parallel-group 52-week Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin in Patients With Type 2 Diabetes Mellitus and Severe Renal Impairment Who Have Inadequate Glycemic Control
Actual Study Start Date :
Aug 16, 2017
Actual Primary Completion Date :
May 16, 2019
Actual Study Completion Date :
Dec 11, 2019

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 milligrams [mg] in appearance) orally once daily for up to 56 weeks.

Drug: Placebo
Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.
Experimental: Sotagliflozin 200 mg

Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 56 weeks.

Drug: Placebo
Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.

Drug: Sotagliflozin
Sotagliflozin 200 mg, tablet, orally, once daily.
Other Names:
  • SAR439954

    		•
    Experimental: Sotagliflozin 400 mg

    Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56 weeks.

    Drug: Sotagliflozin
    Sotagliflozin 200 mg, tablet, orally, once daily.
    Other Names:
  • SAR439954

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo [Baseline to Week 26]

      An analysis of covariance (ANCOVA) model was used for the analysis.

    Secondary Outcome Measures

    1. Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo [Baseline to Week 26]

      An ANCOVA model was used for the analysis.

    2. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 [Baseline to Week 26]

      An ANCOVA model was used for the analysis.

    3. Change From Baseline in Body Weight at Week 26 [Baseline to Week 26]

      An ANCOVA model was used for the analysis.

    4. Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg [Baseline to Week 12]

      An ANCOVA model was used for the analysis.

    5. Change From Baseline in SBP at Week 12 for All Participants [Baseline to Week 12]

      An ANCOVA model was used for the analysis.

    6. Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g) [Baseline to Week 26]

      An ANCOVA model was used for analysis. No Measure of Dispersion was pre-specified to be calculated.

    7. Percentage of Participants With HbA1c <6.5% at Week 26 [Week 26]

    8. Percentage of Participants With HbA1c <7.0% at Week 26 [Week 26]

    9. Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks]

      An adverse event (AE) is any untoward medical occurrence in a participants or clinical investigation participants administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the investigational medicinal product (IMP).

    Other Outcome Measures

    1. Percentage of Participants With Hypoglycemic Events [up to 56.3 weeks]

      Percentage of participants 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].

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion criteria :

    • Participants with Type 2 Diabetes (drug-naïve or on antidiabetic therapy) and documented severe renal insufficiency - CKD4 - defined by an estimated glomerular filtration rate (eGFR) equation (based on the 4 variable modification of diet in renal disease (MDRD) equation) of ≥15 and <30 milliliter per minute (mL/min)/1.73 per meter square (m^2).

    • Signed written informed consent to participate in the study in accordance with local regulations.

    Exclusion criteria:

    • At the time of screening, age <18 years.

    • Hemoglobin A1c (HbA1c) <7% or >11%.

    • Type 1 diabetes.

    • Women of childbearing potential (WOCBP) not willing to use highly effective method(s) of birth control during the study treatment period and the follow-up period, or who are unwilling or unable to be tested for pregnancy during the study.

    • Treatment with an sodium-glucose cotransporter type 2 (SGLT2) inhibitor (canagliflozin, dapagliflozin, empagliflozin) during the last 12 months.

    • Uncontrolled high blood pressure, severe anemia, severe cardiovascular problems, such as heart failure, active cancer, or other conditions that the Investigator believes with result in a short life expectancy, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.

    • Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization.

    The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Investigational Site Number 8405033 Guntersville Alabama United States 35976-2206
    2 Investigational Site Number 8405005 Phoenix Arizona United States 85018-2701
    3 Investigational Site Number 8405007 Little Rock Arkansas United States 72205
    4 Investigational Site Number 8405015 Chula Vista California United States 91910
    5 Investigational Site Number 8405032 La Jolla California United States 92037
    6 Investigational Site Number 8405003 Norco California United States 92860-3611
    7 Investigational Site Number 8405013 Northridge California United States 91324
    8 Investigational Site Number 8405018 San Dimas California United States 91773
    9 Investigational Site Number 8405021 Clearwater Florida United States 33761-2022
    10 Investigational Site Number 8405001 DeLand Florida United States 32720-0834
    11 Investigational Site Number 8405043 Miami Florida United States 33155-4630
    12 Investigational Site Number 8405006 Ocoee Florida United States 34761-4547
    13 Investigational Site Number 8405025 Ormond Beach Florida United States 32174-8187
    14 Investigational Site Number 8405039 Lawrenceville Georgia United States 30046
    15 Investigational Site Number 8405041 Arlington Heights Illinois United States 60005-4197
    16 Investigational Site Number 8405030 Sellersburg Indiana United States 47172-8932
    17 Investigational Site Number 8405019 Lake Charles Louisiana United States 70601
    18 Investigational Site Number 8405034 Flint Michigan United States 48532-3447
    19 Investigational Site Number 8405012 Norfolk Nebraska United States 68701-2669
    20 Investigational Site Number 8405035 Albany New York United States 12206
    21 Investigational Site Number 8405014 Bronx New York United States 10455
    22 Investigational Site Number 8405027 Laurelton New York United States 11413
    23 Investigational Site Number 8405037 New Bern North Carolina United States 28562-5200
    24 Investigational Site Number 8405038 Winston-Salem North Carolina United States 27103
    25 Investigational Site Number 8405009 Dayton Ohio United States 45419-4336
    26 Investigational Site Number 8405004 Beaumont Texas United States 77702
    27 Investigational Site Number 8405036 Dallas Texas United States 75208
    28 Investigational Site Number 8405020 Houston Texas United States 77058
    29 Investigational Site Number 8405026 Houston Texas United States 77099-4307
    30 Investigational Site Number 8405047 Hurst Texas United States 76054
    31 Investigational Site Number 8405031 San Antonio Texas United States 78215
    32 Investigational Site Number 8405016 San Antonio Texas United States 78249-2782
    33 Investigational Site Number 8405008 Layton Utah United States 84041-1200
    34 Investigational Site Number 8405040 Winchester Virginia United States 22601
    35 Investigational Site Number 0325001 Buenos Aires Argentina C1425DES
    36 Investigational Site Number 0325003 Launs Este Argentina B1824KAJ
    37 Investigational Site Number 0325004 Mar Del Plata Argentina B7600
    38 Investigational Site Number 0765003 Belém Brazil 66073-005
    39 Investigational Site Number 0765001 Fortaleza Brazil 60170-195
    40 Investigational Site Number 0765004 Rio De Janeiro Brazil 22271-100
    41 Investigational Site Number 0765002 Sao Paulo Brazil 01244-030
    42 Investigational Site Number 1705004 Barranquilla Colombia 80020
    43 Investigational Site Number 1705005 Bogota Colombia 110221
    44 Investigational Site Number 1705002 Manizales Colombia 170004
    45 Investigational Site Number 1705001 Zipaquira Colombia 250252
    46 Investigational Site Number 2765001 Frankfurt Am Main Germany 60596
    47 Investigational Site Number 2765003 Hannover Germany 30625
    48 Investigational Site Number 2765004 Münster Germany 48145
    49 Investigational Site Number 3485005 Baja Hungary 6500
    50 Investigational Site Number 3485007 Debrecen Hungary 4032
    51 Investigational Site Number 3485004 Pécs Hungary 7624
    52 Investigational Site Number 3765002 Ashkelon Israel 78278
    53 Investigational Site Number 3765001 Haifa Israel 31096
    54 Investigational Site Number 3765007 Kfar-Saba Israel 44281
    55 Investigational Site Number 3765005 Ramat Gan Israel 52621
    56 Investigational Site Number 3765004 Rehovot Israel 7642001
    57 Investigational Site Number 3765003 Tel Aviv Israel 61480
    58 Investigational Site Number 3765006 Zefat Israel 13100
    59 Investigational Site Number 3805003 Catania Italy 95123
    60 Investigational Site Number 3805005 Milano Italy 20132
    61 Investigational Site Number 3805006 Napoli Italy 00181
    62 Investigational Site Number 3805002 Napoli Italy 80138
    63 Investigational Site Number 3805001 Pavia Italy 27100
    64 Investigational Site Number 3805004 Roma Italy 00168
    65 Investigational Site Number 4845007 Guadalajara Jalisco Mexico 44130
    66 Investigational Site Number 4845001 Guadalajara Mexico 44210
    67 Investigational Site Number 4845004 Guadalajara Mexico 44600
    68 Investigational Site Number 4845008 Merida, Yucatan Mexico 97130
    69 Investigational Site Number 4845006 Monterrey, N.L Mexico 64460
    70 Investigational Site Number 4845003 Morelia Mexico 58260
    71 Investigational Site Number 4845002 Queretaro Mexico 76000
    72 Investigational Site Number 4845005 Xalapa Mexico 91020
    73 Investigational Site Number 6165003 Krakow Poland 31-209
    74 Investigational Site Number 6165002 Lodz Poland 92-213
    75 Investigational Site Number 6165004 Oswiecim Poland 32-600
    76 Investigational Site Number 6165005 Puławy Poland 24-100
    77 Investigational Site Number 6165001 Rzeszow Poland 35-055
    78 Investigational Site Number 6425005 Bacau Romania 600238
    79 Investigational Site Number 6425002 Bucuresti Romania 010825
    80 Investigational Site Number 6425003 Bucuresti Romania 020475
    81 Investigational Site Number 6425007 Hunedoara Romania 331057
    82 Investigational Site Number 6425004 Lasi Romania 700503
    83 Investigational Site Number 6425001 Targu-Mures Romania 540142
    84 Investigational Site Number 6435004 Chelyabinsk Russian Federation 4540
    85 Investigational Site Number 6435005 Kemerovo Russian Federation 650002
    86 Investigational Site Number 6435003 Krasnodar Russian Federation 350032
    87 Investigational Site Number 6435006 Novosibirsk Russian Federation 630091
    88 Investigational Site Number 6435001 Saint-Petersburg Russian Federation 194358
    89 Investigational Site Number 7105003 Cape Town South Africa 7505
    90 Investigational Site Number 7105004 Cape Town South Africa 7570
    91 Investigational Site Number 7105001 Johannesburg South Africa 2188
    92 Investigational Site Number 7105002 Pretoria South Africa 0002
    93 Investigational Site Number 7245005 Barcelona Spain 08035
    94 Investigational Site Number 7245007 Barcelona Spain 08036
    95 Investigational Site Number 7245003 Ferrol Spain 15405
    96 Investigational Site Number 7245009 Granada Spain 18012
    97 Investigational Site Number 7245006 Madrid Spain 28041
    98 Investigational Site Number 7245004 Málaga Spain 29010
    99 Investigational Site Number 7245001 Sevilla Spain 41009
    100 Investigational Site Number 7245002 Zaragoza Spain 50009
    101 Investigational Site Number 8045004 Chernivtsi Ukraine 58022
    102 Investigational Site Number 8045006 Kiev Ukraine 02002
    103 Investigational Site Number 8045007 Kyiv Ukraine 02091
    104 Investigational Site Number 8045003 Kyiv Ukraine 04050
    105 Investigational Site Number 8045001 Kyiv Ukraine 3037
    106 Investigational Site Number 8045002 Zaporizhzhia Ukraine 69600

    Sponsors and Collaborators

    • Lexicon Pharmaceuticals
    • Sanofi

    Investigators

    • Study Director: Suman Wason, MD, Lexicon Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Lexicon Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03242018
    Other Study ID Numbers:
    • EFC15166
    • 2016-004906-32
    • U1111-1190-7589
    First Posted:
    Aug 8, 2017
    Last Update Posted:
    Jun 25, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Kidney Diseases
    Renal Insufficiency, Chronic
    Diabetes Mellitus
    Diabetes Mellitus, Type 2
    (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

    Study Results

    Participant Flow

    Recruitment Details Participants took part in the study at 106 investigative sites in United States, Argentina, Brazil, Colombia, Germany, Hungary, Israel, Italy, Mexico, Poland, Romania, Russian Federation, South Africa, Spain, Ukraine from 16 August 2017 to 11 December 2019.
    Pre-assignment Detail A total of 277 participants with a diagnosis of Type 2 Diabetes Mellitus were randomized 1:1:1 to 1 of the 3 treatment groups: Placebo, Sotagliflozin 200 milligram (mg) and Sotagliflozin 400 mg.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Period Title: Overall Study
    STARTED 93 92 92
    COMPLETED 75 78 78
    NOT COMPLETED 18 14 14

    Baseline Characteristics

    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg Total
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks. Total of all reporting groups
    Overall Participants 93 92 92 277
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    68.0
    (8.3)
    66.8
    (10.0)
    67.3
    (9.6)
    67.4
    (9.3)
    Sex: Female, Male (Count of Participants)
    Female
    51
    54.8%
    48
    52.2%
    43
    46.7%
    142
    51.3%
    Male
    42
    45.2%
    44
    47.8%
    49
    53.3%
    135
    48.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    41
    44.1%
    33
    35.9%
    33
    35.9%
    107
    38.6%
    Not Hispanic or Latino
    52
    55.9%
    59
    64.1%
    59
    64.1%
    170
    61.4%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    7
    7.5%
    8
    8.7%
    7
    7.6%
    22
    7.9%
    Asian
    1
    1.1%
    2
    2.2%
    2
    2.2%
    5
    1.8%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    1
    1.1%
    0
    0%
    1
    0.4%
    Black or African American
    6
    6.5%
    7
    7.6%
    3
    3.3%
    16
    5.8%
    White
    76
    81.7%
    73
    79.3%
    78
    84.8%
    227
    81.9%
    More than one race
    3
    3.2%
    1
    1.1%
    2
    2.2%
    6
    2.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Argentina
    7
    7.5%
    3
    3.3%
    3
    3.3%
    13
    4.7%
    Brazil
    9
    9.7%
    7
    7.6%
    8
    8.7%
    24
    8.7%
    Colombia
    5
    5.4%
    4
    4.3%
    5
    5.4%
    14
    5.1%
    Germany
    2
    2.2%
    2
    2.2%
    0
    0%
    4
    1.4%
    Hungary
    1
    1.1%
    3
    3.3%
    0
    0%
    4
    1.4%
    Israel
    7
    7.5%
    2
    2.2%
    8
    8.7%
    17
    6.1%
    Italy
    5
    5.4%
    2
    2.2%
    4
    4.3%
    11
    4%
    Mexico
    10
    10.8%
    11
    12%
    11
    12%
    32
    11.6%
    Poland
    7
    7.5%
    6
    6.5%
    8
    8.7%
    21
    7.6%
    Romania
    2
    2.2%
    6
    6.5%
    4
    4.3%
    12
    4.3%
    Russia
    10
    10.8%
    8
    8.7%
    8
    8.7%
    26
    9.4%
    South Africa
    3
    3.2%
    2
    2.2%
    4
    4.3%
    9
    3.2%
    Spain
    7
    7.5%
    10
    10.9%
    11
    12%
    28
    10.1%
    Ukraine
    2
    2.2%
    8
    8.7%
    4
    4.3%
    14
    5.1%
    United States
    16
    17.2%
    18
    19.6%
    14
    15.2%
    48
    17.3%
    Hemoglobin A1c (HbA1c) (percentage of HbA1c) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage of HbA1c]
    8.38
    (1.06)
    8.28
    (1.03)
    8.25
    (0.87)
    8.30
    (0.99)
    Systolic Blood Pressure (SBP) (millimeter of mercury (mmHg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [millimeter of mercury (mmHg)]
    144.72
    (15.56)
    143.10
    (14.98)
    144.20
    (15.10)
    144.01
    (15.17)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo
    Description An analysis of covariance (ANCOVA) model was used for the analysis.
    Time Frame Baseline to Week 26

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts & washout imputation method.
    Arm/Group Title Placebo Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 93 92
    Least Squares Mean (Standard Error) [percentage of HbA1c]
    -0.11
    (0.151)
    -0.40
    (0.131)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0962
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in Least Square (LS) Means
    Estimated Value -0.29
    Confidence Interval (2-Sided) 95%
    -0.628 to 0.051
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.173
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo
    Description An ANCOVA model was used for the analysis.
    Time Frame Baseline to Week 26

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts & washout imputation method.
    Arm/Group Title Placebo Sotagliflozin 200 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks.
    Measure Participants 93 92
    Least Squares Mean (Standard Error) [percentage of HbA1c]
    -0.11
    (0.151)
    -0.07
    (0.162)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.8124
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value 0.05
    Confidence Interval (2-Sided) 95%
    -0.338 to 0.431
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.196
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
    Description An ANCOVA model was used for the analysis.
    Time Frame Baseline to Week 26

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts & washout imputation method.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 93 92 92
    Least Squares Mean (Standard Error) [millimole per liter (mmol/L)]
    0.069
    (0.4482)
    -0.291
    (0.5056)
    -0.644
    (0.4348)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline FPG as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.5501
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.361
    Confidence Interval (2-Sided) 95%
    -1.5431 to 0.8220
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.6033
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline FPG as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1779
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.714
    Confidence Interval (2-Sided) 95%
    -1.7524 to 0.3246
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.5298
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in Body Weight at Week 26
    Description An ANCOVA model was used for the analysis.
    Time Frame Baseline to Week 26

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts & washout imputation method.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 93 92 92
    Least Squares Mean (Standard Error) [kilogram (kg)]
    0.39
    (0.615)
    -0.43
    (0.480)
    -1.02
    (0.490)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline body weight as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2432
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.82
    Confidence Interval (2-Sided) 95%
    -2.197 to 0.557
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.703
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline body weight as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0487
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.41
    Confidence Interval (2-Sided) 95%
    -2.810 to -0.008
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.715
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg
    Description An ANCOVA model was used for the analysis.
    Time Frame Baseline to Week 12

    Outcome Measure Data

    Analysis Population Description
    Analysis population included all participants with baseline SBP ≥130 mmHg in ITT population where, ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data are imputed using control-based copy reference multiple imputation under the missing not at random framework.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 73 68 73
    Least Squares Mean (Standard Error) [mmHg]
    -2.70
    (1.815)
    -4.84
    (1.882)
    -7.10
    (1.842)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, and country as fixed effects, and baseline SBP as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3954
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -2.14
    Confidence Interval (2-Sided) 95%
    -7.066 to 2.792
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.515
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, and country as fixed effects, and baseline SBP as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0716
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -4.40
    Confidence Interval (2-Sided) 95%
    -9.185 to 0.386
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.442
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in SBP at Week 12 for All Participants
    Description An ANCOVA model was used for the analysis.
    Time Frame Baseline to Week 12

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data are imputed using control-based copy reference multiple imputation under the missing not at random framework.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 93 92 92
    Least Squares Mean (Standard Error) [mmHg]
    -2.50
    (1.762)
    -5.74
    (1.752)
    -7.86
    (1.794)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline SBP as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1232
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -3.24
    Confidence Interval (2-Sided) 95%
    -7.365 to 0.881
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.103
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline SBP as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0098
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -5.36
    Confidence Interval (2-Sided) 95%
    -9.433 to -1.292
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.077
    Estimation Comments
    7. Secondary Outcome
    Title Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g)
    Description An ANCOVA model was used for analysis. No Measure of Dispersion was pre-specified to be calculated.
    Time Frame Baseline to Week 26

    Outcome Measure Data

    Analysis Population Description
    Analysis population included all participants with baseline UACR > 30 mg/g in ITT population where, ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data was imputed using the retrieved dropouts & washout imputation method.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 66 71 75
    Geometric Mean (Standard Error) [percent change]
    -4.56
    (NA)
    -26.99
    (NA)
    -30.66
    (NA)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and log-transformed baseline UACR as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.222
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Percent Difference
    Estimated Value -20.37
    Confidence Interval (2-Sided) 95%
    -44.75 to 14.77
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of mean SBP (<130, ≥130 mmHg) at screening, and country as fixed effects, and log-transformed baseline UACR as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.1965
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Percent Difference
    Estimated Value -21.17
    Confidence Interval (2-Sided) 95%
    -45.05 to 13.10
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Percentage of Participants With HbA1c <6.5% at Week 26
    Description
    Time Frame Week 26

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 93 92 92
    Number [percentage of participants]
    2.2
    2.4%
    5.4
    5.9%
    8.7
    9.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (<130, ≥130 mmHg) at screening.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2420
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Percentage Difference
    Estimated Value 3.2
    Confidence Interval (2-Sided) 95%
    -2.17 to 8.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (<130, ≥130 mmHg) at screening.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0513
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Percentage Difference
    Estimated Value 6.5
    Confidence Interval (2-Sided) 95%
    0.04 to 12.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Percentage of Participants With HbA1c <7.0% at Week 26
    Description
    Time Frame Week 26

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 93 92 92
    Number [percentage of participants]
    4.3
    4.6%
    16.3
    17.7%
    17.4
    18.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (<130, ≥130 mmHg) at screening.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0066
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Percentage Difference
    Estimated Value 12
    Confidence Interval (2-Sided) 95%
    3.48 to 20.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 400 mg
    Comments Percentage difference between treatment groups using the Cochran-Mantel-Haenszel test stratified by the randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of metformin use at screening (Yes, No), and the randomization strata of mean SBP (<130, ≥130 mmHg) at screening.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0043
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Percentage Difference
    Estimated Value 13
    Confidence Interval (2-Sided) 95%
    4.28 to 21.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    10. Secondary Outcome
    Title Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
    Description An adverse event (AE) is any untoward medical occurrence in a participants or clinical investigation participants administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the investigational medicinal product (IMP).
    Time Frame First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population included all randomized participants who received at least one dose of double-blind IMP. Two participants were randomized to Sotagliflozin 400 mg and dosed with Sotagliflozin 200 mg and 400 mg treatments during the study. Data for these participants were summarized in the Sotagliflozin 200 mg arm in the safety population.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 93 94 90
    Number [percentage of participants]
    82.8
    89%
    86.2
    93.7%
    81.1
    88.2%
    11. Other Pre-specified Outcome
    Title Percentage of Participants With Hypoglycemic Events
    Description Percentage of participants 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].
    Time Frame up to 56.3 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population included all randomized participants who received at least 1 dose of double-blind investigational medicinal product (IMP) (regardless of the amount of treatment administered).
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    Measure Participants 93 94 90
    Any hypoglycemia
    40.9
    44%
    40.4
    43.9%
    38.9
    42.3%
    Documented symptomatic hypoglycemia
    35.5
    38.2%
    28.7
    31.2%
    27.8
    30.2%
    Severe or documented symptomatic hypoglycemia
    35.5
    38.2%
    30.9
    33.6%
    27.8
    30.2%

    Adverse Events

    Time Frame Deaths: Up to approximately 60 weeks; Adverse Events: First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks
    Adverse Event Reporting Description Safety population included all randomized participants who received at least one dose of double-blind IMP. Hypoglycemia was captured and handled separately from other adverse events and is reported in the outcome measure section.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance) orally once daily for up to 56.3 weeks. Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 55.3 weeks. Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56.1 weeks.
    All Cause Mortality
    Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/93 (6.5%) 6/94 (6.4%) 3/90 (3.3%)
    Serious Adverse Events
    Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 21/93 (22.6%) 18/94 (19.1%) 20/90 (22.2%)
    Blood and lymphatic system disorders
    Anaemia 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Blood loss anaemia 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Cardiac disorders
    Acute coronary syndrome 2/93 (2.2%) 0/94 (0%) 0/90 (0%)
    Acute myocardial infarction 4/93 (4.3%) 1/94 (1.1%) 0/90 (0%)
    Atrial fibrillation 0/93 (0%) 1/94 (1.1%) 1/90 (1.1%)
    Atrioventricular block complete 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Cardiac failure 2/93 (2.2%) 1/94 (1.1%) 1/90 (1.1%)
    Cardiac failure acute 2/93 (2.2%) 0/94 (0%) 1/90 (1.1%)
    Cardiac failure chronic 2/93 (2.2%) 1/94 (1.1%) 0/90 (0%)
    Cardio-respiratory arrest 1/93 (1.1%) 0/94 (0%) 1/90 (1.1%)
    Coronary artery disease 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Diastolic dysfunction 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Myocardial infarction 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Eye disorders
    Eye haemorrhage 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Gastrointestinal disorders
    Gastrointestinal haemorrhage 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Haemorrhoids 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Inguinal hernia 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Obstructive pancreatitis 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    General disorders
    Asthenia 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Death 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Sudden cardiac death 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Hepatobiliary disorders
    Cholangitis 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Cholelithiasis 0/93 (0%) 1/94 (1.1%) 1/90 (1.1%)
    Infections and infestations
    Bronchitis 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Cellulitis 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Escherichia urinary tract infection 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Gangrene 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Herpes zoster 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Influenza 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Osteomyelitis 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Pneumonia 1/93 (1.1%) 0/94 (0%) 4/90 (4.4%)
    Pneumonia bacterial 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Sepsis 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Urinary tract infection 0/93 (0%) 2/94 (2.1%) 0/90 (0%)
    Injury, poisoning and procedural complications
    Fall 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Femoral neck fracture 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Hip fracture 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Limb injury 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Post procedural haemorrhage 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Radius fracture 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Investigations
    Alanine aminotransferase increased 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Glomerular filtration rate decreased 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Hepatitis C antibody positive 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Metabolism and nutrition disorders
    Fluid overload 1/93 (1.1%) 0/94 (0%) 1/90 (1.1%)
    Hypoglycaemia 0/93 (0%) 2/94 (2.1%) 0/90 (0%)
    Musculoskeletal and connective tissue disorders
    Fistula 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Metatarsalgia 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/93 (0%) 0/94 (0%) 2/90 (2.2%)
    Bladder neoplasm 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Invasive ductal breast carcinoma 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Pancreatic carcinoma 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Papillary thyroid cancer 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Plasma cell myeloma 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Nervous system disorders
    Ischaemic stroke 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Peripheral sensorimotor neuropathy 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Sciatica 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Syncope 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Transient ischaemic attack 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Renal and urinary disorders
    Acute kidney injury 6/93 (6.5%) 1/94 (1.1%) 0/90 (0%)
    Chronic kidney disease 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    End stage renal disease 1/93 (1.1%) 2/94 (2.1%) 3/90 (3.3%)
    Hydronephrosis 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Renal colic 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Renal failure 0/93 (0%) 2/94 (2.1%) 1/90 (1.1%)
    Renal impairment 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 1/93 (1.1%) 1/94 (1.1%) 1/90 (1.1%)
    Chronic obstructive pulmonary disease 1/93 (1.1%) 0/94 (0%) 1/90 (1.1%)
    Chronic respiratory failure 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Painful respiration 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Pulmonary congestion 0/93 (0%) 0/94 (0%) 1/90 (1.1%)
    Pulmonary hypertension 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Pulmonary oedema 0/93 (0%) 0/94 (0%) 2/90 (2.2%)
    Tracheomalacia 1/93 (1.1%) 0/94 (0%) 0/90 (0%)
    Vascular disorders
    Hypertension 0/93 (0%) 1/94 (1.1%) 2/90 (2.2%)
    Peripheral ischaemia 0/93 (0%) 1/94 (1.1%) 0/90 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 44/93 (47.3%) 44/94 (46.8%) 29/90 (32.2%)
    Gastrointestinal disorders
    Diarrhoea 3/93 (3.2%) 5/94 (5.3%) 5/90 (5.6%)
    Infections and infestations
    Influenza 5/93 (5.4%) 5/94 (5.3%) 2/90 (2.2%)
    Nasopharyngitis 4/93 (4.3%) 8/94 (8.5%) 1/90 (1.1%)
    Urinary tract infection 16/93 (17.2%) 10/94 (10.6%) 6/90 (6.7%)
    Investigations
    Glomerular filtration rate decreased 3/93 (3.2%) 10/94 (10.6%) 8/90 (8.9%)
    Metabolism and nutrition disorders
    Hyperkalaemia 2/93 (2.2%) 9/94 (9.6%) 5/90 (5.6%)
    Hyperuricaemia 6/93 (6.5%) 2/94 (2.1%) 1/90 (1.1%)
    Vitamin D deficiency 6/93 (6.5%) 9/94 (9.6%) 3/90 (3.3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 5/93 (5.4%) 3/94 (3.2%) 2/90 (2.2%)
    Renal and urinary disorders
    Renal impairment 7/93 (7.5%) 5/94 (5.3%) 3/90 (3.3%)
    Vascular disorders
    Hypertension 5/93 (5.4%) 1/94 (1.1%) 3/90 (3.3%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Institution must provide any proposed publication or presentation to Sponsor for Sponsor's review, comment and approval at least thirty (30) days prior to the proposed submission for publication date or the proposed presentation date. Sponsor shall have the right to have deleted from the final version of the publication any confidential information, proprietary information, or patentable subject matter.

    Results Point of Contact

    Name/Title Medical Affairs
    Organization Lexicon Pharmaceuticals, Inc.
    Phone (510) 338-6064
    Email medical-information@lexpharma.com
    Responsible Party:
    Lexicon Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03242018
    Other Study ID Numbers:
    • EFC15166
    • 2016-004906-32
    • U1111-1190-7589
    First Posted:
    Aug 8, 2017
    Last Update Posted:
    Jun 25, 2021
    Last Verified:
    Jun 1, 2021