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SOTA-CKD3: Safety and Efficacy Study of Sotagliflozin on Glucose Control in Participants With Type 2 Diabetes, Moderate Impairment of Kidney Function, and Inadequate Blood Sugar Control

Sponsor
Lexicon Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT03242252
Collaborator
Sanofi (Industry)
787
Enrollment
170
Locations
3
Arms
26.3
Actual Duration (Months)
4.6
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate the superiority of Sotagliflozin 200 milligrams (mg) and Sotagliflozin 400 mg versus placebo on HbA1c reduction at 26 Weeks in participants with Type 2 diabetes who have inadequate glycemic control and moderate renal impairment.

Secondary Objectives:

  • To assess the effects of Sotagliflozin 200 mg and 400 mg versus placebo with respect to additional measures of glycemic control, blood pressure, and body weight.

  • To evaluate the safety of Sotagliflozin 200 mg and 400 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 :
787 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
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 Moderate Renal Impairment Who Have Inadequate Glycemic Control
Actual Study Start Date :
Aug 16, 2017
Actual Primary Completion Date :
Mar 25, 2019
Actual Study Completion Date :
Oct 25, 2019

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

Following a 2-week run-in period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks.

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

Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks.

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

Drug: Sotagliflozin
Sotagliflozin 200 mg, tablet, orally once daily. Route of administration: Oral
Other Names:
  • SAR439954

    		•
    Experimental: Sotagliflozin 400 mg

    Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.

    Drug: Sotagliflozin
    Sotagliflozin 200 mg, tablet, orally once daily. Route of administration: Oral
    Other Names:
  • SAR439954

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Change From Baseline in HbA1c at Week 26 [Baseline to Week 26]

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

    Secondary Outcome Measures

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

      An ANCOVA model was used for analysis.

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

      An ANCOVA model was used for analysis.

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

      An ANCOVA model was used for analysis.

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

      An ANCOVA model was used for analysis.

    5. 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.

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

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

    8. Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [Up to 60 weeks]

    Other Outcome Measures

    1. Percentage of Participants With Hypoglycemic Events [Up to 60 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 moderate renal insufficiency defined by an estimated glomerular filtration rate (eGFR) (based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation) of ≥30 and <60 milliliter per minute (mL/min)/1.73 meter square (m^2) (chronic kidney disease [CKD] 3A, 3B).

    • Participants has given written informed consent to participate in the study in accordance with local regulations.

    Exclusion criteria:

    • Hemoglobin A1c (HbA1c) of <7.0% or >11.0%.

    • 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 a sodium-glucose cotransporter type 2 (SGLT2) inhibitor (Canagliflozin, Dapagliflozin, Empagliflozin) during the last 12 months.

    • Uncontrolled high blood pressure.

    • Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or patients with short life expectancy that, according to the Investigator, 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 8404018 Birmingham Alabama United States 35205
    2 Investigational Site Number 8404045 Guntersville Alabama United States 35976-2206
    3 Investigational Site Number 8404004 Phoenix Arizona United States 85018-2701
    4 Investigational Site Number 8404022 Phoenix Arizona United States 85050-7500
    5 Investigational Site Number 8404007 Little Rock Arkansas United States 72205
    6 Investigational Site Number 8404023 Chula Vista California United States 91910
    7 Investigational Site Number 8404044 Gold River California United States 95670
    8 Investigational Site Number 8404011 Los Angeles California United States 90057
    9 Investigational Site Number 8404003 Norco California United States 92860
    10 Investigational Site Number 8404025 Northridge California United States 91324
    11 Investigational Site Number 8404038 San Dimas California United States 91713
    12 Investigational Site Number 8404019 Clearwater Florida United States 33761
    13 Investigational Site Number 8404001 DeLand Florida United States 32720-0834
    14 Investigational Site Number 8404006 Ocoee Florida United States 34761-4547
    15 Investigational Site Number 8404064 Orlando Florida United States 32806
    16 Investigational Site Number 8404043 Ormond Beach Florida United States 32174-8187
    17 Investigational Site Number 8404013 Palmetto Bay Florida United States 33157-5503
    18 Investigational Site Number 8404016 Savannah Georgia United States 31406
    19 Investigational Site Number 8404040 Wauconda Illinois United States 60084-2452
    20 Investigational Site Number 8404036 Lake Charles Louisiana United States 70601
    21 Investigational Site Number 8404020 New Orleans Louisiana United States 70119-6302
    22 Investigational Site Number 8404014 Norfolk Nebraska United States 68701
    23 Investigational Site Number 8404032 Papillion Nebraska United States 68046-3136
    24 Investigational Site Number 8404048 Hackensack New Jersey United States 07601-1963
    25 Investigational Site Number 8404009 Bronx New York United States 10455
    26 Investigational Site Number 8404074 New York New York United States 00000
    27 Investigational Site Number 8404051 Wilmington North Carolina United States 28401-6638
    28 Investigational Site Number 8404028 Winston-Salem North Carolina United States 27103-3914
    29 Investigational Site Number 8404029 Winston-Salem North Carolina United States 27103-4027
    30 Investigational Site Number 8404026 Dayton Ohio United States 45419-4336
    31 Investigational Site Number 8404052 Lansdale Pennsylvania United States 19446-1002
    32 Investigational Site Number 8404031 Anderson South Carolina United States 29621
    33 Investigational Site Number 8404021 Mount Pleasant South Carolina United States 29464
    34 Investigational Site Number 8404056 Chattanooga Tennessee United States 37404
    35 Investigational Site Number 8404015 Austin Texas United States 78726-4061
    36 Investigational Site Number 8404050 Austin Texas United States 78731
    37 Investigational Site Number 8404060 Austin Texas United States 78749
    38 Investigational Site Number 8404005 Beaumont Texas United States 77702
    39 Investigational Site Number 8404035 Dallas Texas United States 75208
    40 Investigational Site Number 8404039 Houston Texas United States 77058
    41 Investigational Site Number 8404055 Houston Texas United States 77099
    42 Investigational Site Number 8404012 Hurst Texas United States 76054
    43 Investigational Site Number 8404033 Lampasas Texas United States 76550-1820
    44 Investigational Site Number 8404053 McAllen Texas United States 78504
    45 Investigational Site Number 8404057 Round Rock Texas United States 78681
    46 Investigational Site Number 8404059 San Antonio Texas United States 78212
    47 Investigational Site Number 8404010 San Antonio Texas United States 78249-2782
    48 Investigational Site Number 8404008 Layton Utah United States 84041-1200
    49 Investigational Site Number 8404042 Renton Washington United States 98057
    50 Investigational Site Number 8404041 Seattle Washington United States 98105
    51 Investigational Site Number 8404047 Kenosha Wisconsin United States 53144
    52 Investigational Site Number 0324001 Buenos Aires Argentina C1429BWN
    53 Investigational Site Number 0324002 Caba Argentina 1425DES
    54 Investigational Site Number 0324005 Ciudad Autónoma Buenos Aires Argentina 1205
    55 Investigational Site Number 0324008 Cordoba Argentina 5000
    56 Investigational Site Number 0324006 Córdoba Argentina X5008HHW
    57 Investigational Site Number 0324009 La Plata Argentina 1900
    58 Investigational Site Number 0324007 Mar Del Plata Argentina B7600FYK
    59 Investigational Site Number 0764007 Belo Horizonte Brazil 30150-240
    60 Investigational Site Number 0764001 Belém Brazil 66073-005
    61 Investigational Site Number 0764002 Curitiba Brazil 80030-480
    62 Investigational Site Number 0764008 Curitiba Brazil 80810-040
    63 Investigational Site Number 0764005 Rio De Janeiro Brazil 22271-100
    64 Investigational Site Number 0764006 Sao Paulo Brazil 04266-010
    65 Investigational Site Number 0764004 São Paulo Brazil 01244-030
    66 Investigational Site Number 1244007 Brampton Canada L6S 0C6
    67 Investigational Site Number 1244004 Burlington Canada L7R 1A4
    68 Investigational Site Number 1244005 Etobicoke Canada M9R 4E1
    69 Investigational Site Number 1244006 Laval Canada H7T 2P5
    70 Investigational Site Number 1244009 Montreal Canada H4A 2C6
    71 Investigational Site Number 1244010 Ottawa Canada K2J 0V2
    72 Investigational Site Number 1244003 Thornhill Canada L4J 8L7
    73 Investigational Site Number 1244002 Toronto Canada M4C 5T2
    74 Investigational Site Number 1244008 Toronto Canada M4G 3E8
    75 Investigational Site Number 1244001 Vancouver Canada V5Y 3W2
    76 Investigational Site Number 1704008 Barranquilla Colombia 080001
    77 Investigational Site Number 1704007 Barranquilla Colombia 80020
    78 Investigational Site Number 1704004 Bogota Colombia 110221
    79 Investigational Site Number 1704009 Bogota Colombia 110911
    80 Investigational Site Number 1704006 Ibague Colombia 730006
    81 Investigational Site Number 1704001 Manizales Colombia 170004
    82 Investigational Site Number 1704002 Medellin / Antioquia Colombia 50021
    83 Investigational Site Number 1704005 Zipaquira Colombia 250252
    84 Investigational Site Number 2764001 Frankfurt Am Main Germany 60596
    85 Investigational Site Number 2764002 Hamburg Germany 21073
    86 Investigational Site Number 2764003 Münster Germany 48145
    87 Investigational Site Number 3484008 Baja Hungary 6500
    88 Investigational Site Number 3484012 Baja Hungary 6500
    89 Investigational Site Number 3484002 Balatonfured Hungary 8230
    90 Investigational Site Number 3484007 Budapest Hungary 1033
    91 Investigational Site Number 3484011 Debrecen Hungary 4025
    92 Investigational Site Number 3484005 Debrecen Hungary 4032
    93 Investigational Site Number 3484001 Gyula Hungary 5700
    94 Investigational Site Number 3484010 Nyiregyhaza Hungary 4405
    95 Investigational Site Number 3484013 Nyregyhza Hungary 4400
    96 Investigational Site Number 3484004 Pécs Hungary 7623
    97 Investigational Site Number 3764001 Ashkelon Israel 7830604
    98 Investigational Site Number 3764010 Be'Er-Sheva Israel 84101
    99 Investigational Site Number 3764007 Haifa Israel 31096
    100 Investigational Site Number 3764009 Kfar-Saba Israel 44281
    101 Investigational Site Number 3764011 Kfar-Saba Israel 44281
    102 Investigational Site Number 3764003 Nahariya Israel 22100
    103 Investigational Site Number 3764004 Petach Tikva Israel 49100
    104 Investigational Site Number 3764006 Ramat Gan Israel 52621
    105 Investigational Site Number 3764005 Rehovot Israel 76100
    106 Investigational Site Number 3764002 Tel Aviv Israel 61480
    107 Investigational Site Number 3764008 Zefat Israel 13100
    108 Investigational Site Number 3764013 Zerifin Israel 70300
    109 Investigational Site Number 3804007 Catania Italy 95123
    110 Investigational Site Number 3804005 Milano Italy 20122
    111 Investigational Site Number 3804004 Milano Italy 20132
    112 Investigational Site Number 3804008 Naples Italy 80131
    113 Investigational Site Number 3804002 Napoli Italy 80138
    114 Investigational Site Number 3804003 Roma Italy 00168
    115 Investigational Site Number 3804006 Siena Italy 53100
    116 Investigational Site Number 4844009 Chihuahua Chihuahua Mexico 31217
    117 Investigational Site Number 4844008 Durango, Durango Mexico 34080
    118 Investigational Site Number 4844001 Guadalajara Mexico 44210
    119 Investigational Site Number 4844003 Guadalajara Mexico 44600
    120 Investigational Site Number 4844006 Merida, Yucatan Mexico 97130
    121 Investigational Site Number 4844005 Monterrey Mexico 64460
    122 Investigational Site Number 4844004 Xalapa Mexico 91020
    123 Investigational Site Number 6164002 Białystok Poland 15-435
    124 Investigational Site Number 6164006 Katowice Poland 40-081
    125 Investigational Site Number 6164010 Krakow Poland 30-033
    126 Investigational Site Number 6164009 Krakow Poland 30-363
    127 Investigational Site Number 6164004 Krakow Poland 31-209
    128 Investigational Site Number 6164008 Krakow Poland 31-530
    129 Investigational Site Number 6164011 Lodz Poland 92-213
    130 Investigational Site Number 6164005 Oswiecim Poland 32-600
    131 Investigational Site Number 6164003 Rzeszow Poland 35-055
    132 Investigational Site Number 6164012 Skierniewice Poland 96-100
    133 Investigational Site Number 6164007 Warszawa Poland 02-507
    134 Investigational Site Number 6424002 Bacau Romania 600154
    135 Investigational Site Number 6424001 Bacau Romania 600238
    136 Investigational Site Number 6424004 Bucuresti Romania 010825
    137 Investigational Site Number 6424009 Bucuresti Romania 013764
    138 Investigational Site Number 6424010 Bucuresti Romania 040172
    139 Investigational Site Number 6424006 Hunedoara Romania 331057
    140 Investigational Site Number 6424011 Oradea Romania 410159
    141 Investigational Site Number 6424003 Targu-Mures Romania 540142
    142 Investigational Site Number 6434003 Chelyabinsk Russian Federation 454047
    143 Investigational Site Number 6434005 Kemerovo Russian Federation 650002
    144 Investigational Site Number 6434002 Krasnodar Russian Federation 3500
    145 Investigational Site Number 6434004 Novosibirsk Russian Federation 630091
    146 Investigational Site Number 6434001 St. Petersburg Russian Federation 194358
    147 Investigational Site Number 6434006 Yaroslavl Russian Federation 150003
    148 Investigational Site Number 7104008 Cape Town South Africa 7531
    149 Investigational Site Number 7104002 Cape Town South Africa 7570
    150 Investigational Site Number 7104001 Johannesburg South Africa 1685
    151 Investigational Site Number 7104010 Johannesburg South Africa 2188
    152 Investigational Site Number 7104005 Johannesburg South Africa 2198
    153 Investigational Site Number 7104006 Pretoria South Africa 0002
    154 Investigational Site Number 7244011 Barcelona Spain 08035
    155 Investigational Site Number 7244007 Granada Spain 18012
    156 Investigational Site Number 7244003 Madrid Spain 28041
    157 Investigational Site Number 7244006 Palma De Mallorca Spain 07010
    158 Investigational Site Number 7244001 Sevilla Spain 41071
    159 Investigational Site Number 7244002 Valencia Spain 46014
    160 Investigational Site Number 7244009 Zaragoza Spain 50009
    161 Investigational Site Number 8044004 Dnipropetrovsk Ukraine 49005
    162 Investigational Site Number 8044007 Kharkiv Ukraine 61106
    163 Investigational Site Number 8044010 Kharkiv Ukraine 61166
    164 Investigational Site Number 8044008 Kiev Ukraine 02002
    165 Investigational Site Number 8044003 Kiev Ukraine 04050
    166 Investigational Site Number 8044009 Kyiv Ukraine 02091
    167 Investigational Site Number 8044001 Kyiv Ukraine 03037
    168 Investigational Site Number 8044006 Kyiv Ukraine 03049
    169 Investigational Site Number 8044005 Lviv Ukraine 79010
    170 Investigational Site Number 8044002 Zaporizhia 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:
    NCT03242252
    Other Study ID Numbers:
    • EFC14837
    • 2016-004889-26
    • U1111-1187-8662
    First Posted:
    Aug 8, 2017
    Last Update Posted:
    Jun 25, 2021
    Last Verified:
    May 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 166 investigative sites in the United States, Argentina, Brazil, Canada, Colombia, Germany, Hungary, Israel, Italy, Mexico, Poland, Romania, Russian Federation, South Africa, Spain, and Ukraine from 16 August 2017 to 25 October 2019.
    Pre-assignment Detail Participants with a diagnosis of Type 2 Diabetes Mellitus were enrolled in 1 of 3 treatment groups: Placebo or Sotagliflozin 200 milligrams (mg) or Sotagliflozin 400 mg. Participants were randomly assigned in the ratio of 1:1:1 to these reporting groups.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.
    Period Title: Overall Study
    STARTED 260 263 264
    COMPLETED 224 240 232
    NOT COMPLETED 36 23 32

    Baseline Characteristics

    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg Total
    Arm/Group Description Following a 2-week run-in period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks. Total of all reporting groups
    Overall Participants 260 263 264 787
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    69.3
    (8.1)
    69.6
    (7.5)
    69.5
    (8.2)
    69.5
    (7.9)
    Sex: Female, Male (Count of Participants)
    Female
    111
    42.7%
    120
    45.6%
    112
    42.4%
    343
    43.6%
    Male
    149
    57.3%
    143
    54.4%
    152
    57.6%
    444
    56.4%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    67
    25.8%
    67
    25.5%
    64
    24.2%
    198
    25.2%
    Not Hispanic or Latino
    193
    74.2%
    196
    74.5%
    200
    75.8%
    589
    74.8%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    15
    5.8%
    9
    3.4%
    20
    7.6%
    44
    5.6%
    Asian
    5
    1.9%
    7
    2.7%
    8
    3%
    20
    2.5%
    Native Hawaiian or Other Pacific Islander
    1
    0.4%
    1
    0.4%
    0
    0%
    2
    0.3%
    Black or African American
    12
    4.6%
    14
    5.3%
    15
    5.7%
    41
    5.2%
    White
    220
    84.6%
    231
    87.8%
    215
    81.4%
    666
    84.6%
    More than one race
    3
    1.2%
    0
    0%
    3
    1.1%
    6
    0.8%
    Unknown or Not Reported
    4
    1.5%
    1
    0.4%
    3
    1.1%
    8
    1%
    Region of Enrollment (participants) [Number]
    Colombia
    12
    4.6%
    6
    2.3%
    14
    5.3%
    32
    4.1%
    Argentina
    8
    3.1%
    8
    3%
    8
    3%
    24
    3%
    Romania
    6
    2.3%
    14
    5.3%
    13
    4.9%
    33
    4.2%
    Hungary
    21
    8.1%
    23
    8.7%
    13
    4.9%
    57
    7.2%
    United States
    66
    25.4%
    72
    27.4%
    62
    23.5%
    200
    25.4%
    Ukraine
    12
    4.6%
    13
    4.9%
    14
    5.3%
    39
    5%
    Spain
    9
    3.5%
    10
    3.8%
    15
    5.7%
    34
    4.3%
    Russia
    15
    5.8%
    10
    3.8%
    14
    5.3%
    39
    5%
    Canada
    11
    4.2%
    18
    6.8%
    12
    4.5%
    41
    5.2%
    Poland
    29
    11.2%
    23
    8.7%
    32
    12.1%
    84
    10.7%
    Brazil
    22
    8.5%
    22
    8.4%
    22
    8.3%
    66
    8.4%
    Italy
    5
    1.9%
    6
    2.3%
    8
    3%
    19
    2.4%
    South Africa
    7
    2.7%
    3
    1.1%
    12
    4.5%
    22
    2.8%
    Mexico
    14
    5.4%
    13
    4.9%
    7
    2.7%
    34
    4.3%
    Israel
    23
    8.8%
    17
    6.5%
    16
    6.1%
    56
    7.1%
    Germany
    0
    0%
    5
    1.9%
    2
    0.8%
    7
    0.9%
    Hemoglobin A1c (HbA1c) (percentage of HbA1c) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [percentage of HbA1c]
    8.33
    (1.00)
    8.33
    (0.9)
    8.31
    (0.94)
    8.32
    (0.95)
    Systolic Blood Pressure (SBP) (millimeter of mercury (mmHg)) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [millimeter of mercury (mmHg)]
    140.59
    (14.59)
    140.31
    (15.15)
    141.71
    (15.01)
    140.87
    (14.91)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline in HbA1c at Week 26
    Description An Analysis of covariance (ANCOVA) model was used for analysis.
    Time Frame Baseline to Week 26

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population included all randomized participants or participants analyzed according to their randomized treatment. Missing data was 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 period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.
    Measure Participants 260 263 264
    Least Squares Mean (Standard Error) [percentage of HbA1c]
    -0.22
    (0.061)
    -0.32
    (0.060)
    -0.46
    (0.060)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 200 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, randomization stratum of Chronic Kidney Disease (CKD) stage (3A, 3B) 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 0.2095
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in Least Squares (LS) Means
    Estimated Value -0.1
    Confidence Interval (2-Sided) 95%
    -0.245 to 0.054
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.076
    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, randomization stratum of CKD stage (3A, 3B) 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 0.0021
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.24
    Confidence Interval (2-Sided) 95%
    -0.386 to -0.085
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.077
    Estimation Comments
    2. Secondary Outcome
    Title Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
    Description An ANCOVA model was used for analysis.
    Time Frame Baseline to Week 26

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants or participants analyzed according to their randomized treatment. 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 period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.
    Measure Participants 260 263 264
    Least Squares Mean (Standard Error) [millimole per liter (mmol/L)]
    -0.374
    (0.1949)
    -0.961
    (0.1715)
    -0.852
    (0.1668)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 200 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, randomization stratum of CKD stage (3A, 3B) 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 0.0144
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.587
    Confidence Interval (2-Sided) 95%
    -1.0564 to -0.1169
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.2397
    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, randomization stratum of CKD stage (3A, 3B) 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 0.0436
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.478
    Confidence Interval (2-Sided) 95%
    -0.942 to -0.0136
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.2368
    Estimation Comments
    3. Secondary Outcome
    Title Change From Baseline in SBP for Participants With Baseline SBP ≥130 mmHg at Week 12
    Description An ANCOVA model was used for analysis.
    Time Frame Baseline to Week 12

    Outcome Measure Data

    Analysis Population Description
    Analysis population included participants with baseline SBP ≥130 mmHg in ITT population where, ITT population included all randomized participants or participants analyzed according to their randomized treatment. 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 period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.
    Measure Participants 175 162 182
    Least Squares Mean (Standard Error) [mmHg]
    -5.18
    (1.462)
    -7.46
    (1.597)
    -7.71
    (1.247)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 200 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 stratum of CKD stage (3A, 3B) 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 0.2627
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -2.28
    Confidence Interval (2-Sided) 95%
    -6.265 to 1.709
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.034
    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 stratum of CKD stage (3A, 3B) 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 0.1602
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -2.53
    Confidence Interval (2-Sided) 95%
    -6.052 to 1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.799
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in SBP at Week 12 for All Participants
    Description An ANCOVA model was used for analysis.
    Time Frame Baseline to Week 12

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants or participants analyzed according to their randomized treatment. 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 period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.
    Measure Participants 260 263 264
    Least Squares Mean (Standard Error) [mmHg]
    -3.31
    (1.037)
    -4.91
    (1.010)
    -4.94
    (0.983)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 200 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, randomization stratum of CKD stage (3A, 3B) at screening, country as fixed effects, and baseline SBP as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2212
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.59
    Confidence Interval (2-Sided) 95%
    -4.142 to 0.958
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.301
    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, randomization stratum of CKD stage (3A, 3B) at screening, country as fixed effects, and baseline SBP as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2089
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.63
    Confidence Interval (2-Sided) 95%
    -4.171 to 0.912
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.297
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in Body Weight at Week 26
    Description An ANCOVA model was used for analysis.
    Time Frame Baseline to Week 26

    Outcome Measure Data

    Analysis Population Description
    ITT population included all randomized participants or participants analyzed according to their randomized treatment. 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 period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.
    Measure Participants 260 263 264
    Least Squares Mean (Standard Error) [kilogram (kg)]
    -0.38
    (0.262)
    -1.66
    (0.246)
    -1.20
    (0.257)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 200 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, randomization stratum of CKD stage (3A, 3B) at screening, country as fixed effects, and baseline body weight as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value < 0.0001
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -1.28
    Confidence Interval (2-Sided) 95%
    -1.92 to -0.644
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.326
    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, randomization stratum of CKD stage (3A, 3B) at screening, country as fixed effects, and baseline body weight as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0155
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Difference in LS Means
    Estimated Value -0.82
    Confidence Interval (2-Sided) 95%
    -1.487 to -0.156
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.339
    Estimation Comments
    6. 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 participants with baseline UACR >30 mg/g in ITT population where, ITT population included all randomized participants or participants analyzed according to their randomized treatment. Missing data was 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 period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.
    Measure Participants 260 263 264
    Geometric Mean (Standard Error) [percent change]
    -18.71
    (NA)
    -43.68
    (NA)
    -48.12
    (NA)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 200 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, randomization stratum of CKD stage (3A, 3B) at screening, country as fixed effects, and and log-transformed baseline UACR as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0015
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Percent Difference
    Estimated Value -30.72
    Confidence Interval (2-Sided) 95%
    -44.78 to -13.07
    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, randomization stratum of CKD stage (3A, 3B) at screening, country as fixed effects, and and log-transformed baseline UACR as a covariate.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0003
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Percent Difference
    Estimated Value -36.18
    Confidence Interval (2-Sided) 95%
    -49.91 to -18.68
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. 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 or participants analyzed according to their randomized treatment.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.
    Measure Participants 260 263 264
    Number [percentage of participants]
    4.2
    1.6%
    5.7
    2.2%
    5.7
    2.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 200 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 mean SBP (<130, ≥130 mmHg) at screening and randomization strata of CKD stage (3A, 3B) at screening.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4328
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Percentage Difference
    Estimated Value 1.5
    Confidence Interval (2-Sided) 95%
    -2.23 to 5.21
    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 mean SBP (<130, ≥130 mmHg) at screening and randomization strata of CKD stage (3A, 3B) at screening.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.4328
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Percentage Difference
    Estimated Value 1.5
    Confidence Interval (2-Sided) 95%
    -2.2 to 5.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. 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 or participants analyzed according to their randomized treatment.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks.
    Measure Participants 260 263 264
    Number [percentage of participants]
    13.5
    5.2%
    19.4
    7.4%
    20.8
    7.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Sotagliflozin 200 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 mean SBP (<130, ≥130 mmHg) at screening and randomization strata of CKD stage (3A, 3B) at screening.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.0614
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Percentage Difference
    Estimated Value 6
    Confidence Interval (2-Sided) 95%
    -0.23 to 12.21
    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 mean SBP (<130, ≥130 mmHg) at screening and randomization strata of CKD stage (3A, 3B) at screening.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.023
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter Percentage Difference
    Estimated Value 7.4
    Confidence Interval (2-Sided) 95%
    1.08 to 13.65
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    9. Secondary Outcome
    Title Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
    Description
    Time Frame Up to 60 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least 1 dose of study drug analyzed according to the treatment actually received.
    Arm/Group Title Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Arm/Group Description Following a 2-week run-in period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Four participants randomized to sotagliflozin 400 mg were dosed with both sotagliflozin 200 mg and 400 mg. These participants were included in the sotagliflozin 200 mg arm in the safety population. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks. Four participants randomized to sotagliflozin 400 mg were dosed with both sotagliflozin 200 mg and 400 mg. These participants were included in the sotagliflozin 200 mg arm in the safety population.
    Measure Participants 260 267 260
    Number [percentage of participants]
    78.1
    30%
    76.8
    29.2%
    74.2
    28.1%
    10. 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 60 weeks

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least 1 dose of study drug analyzed according to the treatment actually received.
    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 54 weeks. Following a 2-week run-in phase, participants received two tablets, 1 Sotagliflozin 200 mg tablet and 1 placebo tablet (identical to Sotagliflozin 200 mg in appearance), orally once daily for up to 58 weeks. Four participants randomized to Sotagliflozin 400 mg were dosed with both Sotagliflozin 200 mg and 400 mg. These participants were included in the Sotagliflozin 200 mg arm in the safety population. Following a 2-week run-in phase, participants received Sotagliflozin 400 mg, administered as two 200 mg Sotagliflozin tablets, orally once daily for up to 60 weeks. Four participants randomized to Sotagliflozin 400 mg were dosed with both Sotagliflozin 200 mg and 400 mg. These participants were included in the Sotagliflozin 200 mg arm in the safety population.
    Measure Participants 260 267 260
    Any hypoglycemia
    38.1
    14.7%
    41.9
    15.9%
    35.4
    13.4%
    Documented symptomatic hypoglycemia
    26.9
    10.3%
    29.6
    11.3%
    22.3
    8.4%
    Severe or documented symptomatic hypoglycemia
    26.9
    10.3%
    29.6
    11.3%
    22.3
    8.4%

    Adverse Events

    Time Frame Up to 60 weeks
    Adverse Event Reporting Description Safety population included all participants who received at least 1 dose of study drug analyzed according to the treatment actually received. Four participants randomized to sotagliflozin 400 mg were dosed with both sotagliflozin 200 mg and 400 mg. These participants were included in the sotagliflozin 200 mg arm in the safety population. 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 period, participants received two placebo tablets (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 54 weeks. Following a 2-week run-in period, participants received two tablets, 1 sotagliflozin 200 mg tablet and 1 placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily, before the first meal of the day for up to 58 weeks. Four participants randomized to sotagliflozin 400 mg were dosed with both sotagliflozin 200 mg and 400 mg. These participants were included in the sotagliflozin 200 mg arm in the safety population. Following a 2-week run-in period, participants received sotagliflozin 400 mg, administered as two 200 mg sotagliflozin tablets, orally once daily, before the first meal of the day for up to 60 weeks. Four participants randomized to sotagliflozin 400 mg were dosed with both sotagliflozin 200 mg and 400 mg. These participants were included in the sotagliflozin 200 mg arm in the safety population.
    All Cause Mortality
    Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/260 (1.2%) 2/267 (0.7%) 5/260 (1.9%)
    Serious Adverse Events
    Placebo Sotagliflozin 200 mg Sotagliflozin 400 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 48/260 (18.5%) 43/267 (16.1%) 44/260 (16.9%)
    Cardiac disorders
    Acute myocardial infarction 2/260 (0.8%) 2/267 (0.7%) 2/260 (0.8%)
    Angina pectoris 1/260 (0.4%) 1/267 (0.4%) 0/260 (0%)
    Angina unstable 0/260 (0%) 4/267 (1.5%) 1/260 (0.4%)
    Arrhythmia 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Atrial fibrillation 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Atrial flutter 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Cardiac arrest 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Cardiac failure 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Cardiac failure acute 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Cardiac failure chronic 1/260 (0.4%) 0/267 (0%) 2/260 (0.8%)
    Cardiac failure congestive 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Cardio-respiratory arrest 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Coronary artery disease 2/260 (0.8%) 0/267 (0%) 1/260 (0.4%)
    Coronary artery insufficiency 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Coronary artery stenosis 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Myocardial infarction 1/260 (0.4%) 1/267 (0.4%) 3/260 (1.2%)
    Myocardial ischaemia 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Pericarditis 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Eye disorders
    Glaucoma 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Iris neovascularisation 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Gastrointestinal disorders
    Abdominal hernia 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Abdominal pain 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Gastric haemorrhage 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Haemorrhoids 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Large intestine polyp 0/260 (0%) 0/267 (0%) 2/260 (0.8%)
    Lower gastrointestinal haemorrhage 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Small intestinal obstruction 0/260 (0%) 2/267 (0.7%) 0/260 (0%)
    Umbilical hernia 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Mallory-Weiss syndrome 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    General disorders
    Cardiac death 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Non-cardiac chest pain 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Peripheral swelling 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Hepatobiliary disorders
    Cholelithiasis 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Drug-induced liver injury 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Liver injury 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Infections and infestations
    Abscess limb 2/260 (0.8%) 0/267 (0%) 0/260 (0%)
    Appendicitis 0/260 (0%) 2/267 (0.7%) 0/260 (0%)
    Bronchitis 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Cellulitis 1/260 (0.4%) 1/267 (0.4%) 1/260 (0.4%)
    Corneal abscess 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Enterococcal infection 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Funguria 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Gangrene 2/260 (0.8%) 0/267 (0%) 0/260 (0%)
    Infective periostitis 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Pneumonia 1/260 (0.4%) 2/267 (0.7%) 1/260 (0.4%)
    Sepsis pasteurella 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Septic shock 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Tick-borne viral encephalitis 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Urinary tract infection 0/260 (0%) 3/267 (1.1%) 0/260 (0%)
    Viral upper respiratory tract infection 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Wound infection 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Injury, poisoning and procedural complications
    Ankle fracture 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Craniocerebral injury 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Limb injury 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Procedural shock 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Rib fracture 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Tibia fracture 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Investigations
    Blood creatinine increased 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Blood pressure increased 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Metabolism and nutrition disorders
    Diabetic metabolic decompensation 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Hyperkalaemia 1/260 (0.4%) 1/267 (0.4%) 1/260 (0.4%)
    Hypoglycaemia 1/260 (0.4%) 1/267 (0.4%) 2/260 (0.8%)
    Hyponatraemia 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Type 2 diabetes mellitus 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Musculoskeletal and connective tissue disorders
    Foot deformity 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Lumbar spinal stenosis 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Osteoarthritis 2/260 (0.8%) 1/267 (0.4%) 1/260 (0.4%)
    Tenosynovitis 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell lymphoma 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Basal cell carcinoma 3/260 (1.2%) 0/267 (0%) 1/260 (0.4%)
    Breast cancer 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Breast cancer female 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Lipoma 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Malignant melanoma of eyelid 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Neuroendocrine tumour 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Plasma cell myeloma 1/260 (0.4%) 0/267 (0%) 1/260 (0.4%)
    Prostate cancer 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Rectal adenocarcinoma 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Squamous cell carcinoma of skin 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Uterine neoplasm 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Nervous system disorders
    Basal ganglia infarction 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Cerebrovascular accident 1/260 (0.4%) 3/267 (1.1%) 1/260 (0.4%)
    Diabetic neuropathy 1/260 (0.4%) 0/267 (0%) 1/260 (0.4%)
    Embolic stroke 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Haemorrhagic stroke 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Hemiparesis 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Hypoglycaemic unconsciousness 0/260 (0%) 2/267 (0.7%) 1/260 (0.4%)
    Ischaemic stroke 2/260 (0.8%) 2/267 (0.7%) 0/260 (0%)
    Loss of consciousness 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Syncope 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Transient ischaemic attack 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Cerebral haemorrhage 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Psychiatric disorders
    Delirium 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Panic attack 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/260 (0%) 0/267 (0%) 2/260 (0.8%)
    Chronic kidney disease 1/260 (0.4%) 0/267 (0%) 2/260 (0.8%)
    End stage renal disease 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Nephrolithiasis 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Nephrotic syndrome 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Renal impairment 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Urinary retention 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/260 (0%) 1/267 (0.4%) 1/260 (0.4%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Chronic obstructive pulmonary disease 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Dyspnoea 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Pleural effusion 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Pulmonary embolism 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Respiratory failure 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Vocal cord polyp 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Skin and subcutaneous tissue disorders
    Diabetic foot 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Ingrowing nail 1/260 (0.4%) 0/267 (0%) 0/260 (0%)
    Skin ulcer 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Vascular disorders
    Deep vein thrombosis 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Extremity necrosis 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Femoral artery aneurysm 0/260 (0%) 1/267 (0.4%) 0/260 (0%)
    Hypotension 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Peripheral arterial occlusive disease 0/260 (0%) 0/267 (0%) 1/260 (0.4%)
    Peripheral artery stenosis 0/260 (0%) 2/267 (0.7%) 0/260 (0%)
    Peripheral ischaemia 0/260 (0%) 0/267 (0%) 2/260 (0.8%)
    Peripheral artery occlusion 0/260 (0%) 1/267 (0.4%) 0/260 (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 80/260 (30.8%) 72/267 (27%) 77/260 (29.6%)
    Gastrointestinal disorders
    Diarrhoea 13/260 (5%) 15/267 (5.6%) 22/260 (8.5%)
    Infections and infestations
    Nasopharyngitis 13/260 (5%) 7/267 (2.6%) 12/260 (4.6%)
    Upper respiratory tract infection 18/260 (6.9%) 16/267 (6%) 13/260 (5%)
    Urinary tract infection 21/260 (8.1%) 19/267 (7.1%) 21/260 (8.1%)
    Metabolism and nutrition disorders
    Vitamin D deficiency 30/260 (11.5%) 24/267 (9%) 24/260 (9.2%)

    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:
    NCT03242252
    Other Study ID Numbers:
    • EFC14837
    • 2016-004889-26
    • U1111-1187-8662
    First Posted:
    Aug 8, 2017
    Last Update Posted:
    Jun 25, 2021
    Last Verified:
    May 1, 2021