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 (SOTA-CKD3)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Chronic Kidney Disease Stage 3
• Intervention / Treatment: Drug: Placebo; Drug: Sotagliflozin

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 Type: Interventional
• Enrollment (Actual): 787
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1429BWN
    • Investigational Site Number 0324001
  • Caba, Argentina, 1425DES
    • Investigational Site Number 0324002
  • Ciudad Autónoma Buenos Aires, Argentina, 1205
    • Investigational Site Number 0324005
  • Cordoba, Argentina, 5000
    • Investigational Site Number 0324008
  • Córdoba, Argentina, X5008HHW
    • Investigational Site Number 0324006
  • La Plata, Argentina, 1900
    • Investigational Site Number 0324009
  • Mar Del Plata, Argentina, B7600FYK
    • Investigational Site Number 0324007
• Brazil
  • Belo Horizonte, Brazil, 30150-240
    • Investigational Site Number 0764007
  • Belém, Brazil, 66073-005
    • Investigational Site Number 0764001
  • Curitiba, Brazil, 80030-480
    • Investigational Site Number 0764002
  • Curitiba, Brazil, 80810-040
    • Investigational Site Number 0764008
  • Rio De Janeiro, Brazil, 22271-100
    • Investigational Site Number 0764005
  • Sao Paulo, Brazil, 04266-010
    • Investigational Site Number 0764006
  • São Paulo, Brazil, 01244-030
    • Investigational Site Number 0764004
• Canada
  • Brampton, Canada, L6S 0C6
    • Investigational Site Number 1244007
  • Burlington, Canada, L7R 1A4
    • Investigational Site Number 1244004
  • Etobicoke, Canada, M9R 4E1
    • Investigational Site Number 1244005
  • Laval, Canada, H7T 2P5
    • Investigational Site Number 1244006
  • Montreal, Canada, H4A 2C6
    • Investigational Site Number 1244009
  • Ottawa, Canada, K2J 0V2
    • Investigational Site Number 1244010
  • Thornhill, Canada, L4J 8L7
    • Investigational Site Number 1244003
  • Toronto, Canada, M4C 5T2
    • Investigational Site Number 1244002
  • Toronto, Canada, M4G 3E8
    • Investigational Site Number 1244008
  • Vancouver, Canada, V5Y 3W2
    • Investigational Site Number 1244001
• Colombia
  • Barranquilla, Colombia, 080001
    • Investigational Site Number 1704008
  • Barranquilla, Colombia, 80020
    • Investigational Site Number 1704007
  • Bogota, Colombia, 110221
    • Investigational Site Number 1704004
  • Bogota, Colombia, 110911
    • Investigational Site Number 1704009
  • Ibague, Colombia, 730006
    • Investigational Site Number 1704006
  • Manizales, Colombia, 170004
    • Investigational Site Number 1704001
  • Medellin / Antioquia, Colombia, 50021
    • Investigational Site Number 1704002
  • Zipaquira, Colombia, 250252
    • Investigational Site Number 1704005
• Germany
  • Frankfurt Am Main, Germany, 60596
    • Investigational Site Number 2764001
  • Hamburg, Germany, 21073
    • Investigational Site Number 2764002
  • Münster, Germany, 48145
    • Investigational Site Number 2764003
• Hungary
  • Baja, Hungary, 6500
    • Investigational Site Number 3484008
  • Baja, Hungary, 6500
    • Investigational Site Number 3484012
  • Balatonfured, Hungary, 8230
    • Investigational Site Number 3484002
  • Budapest, Hungary, 1033
    • Investigational Site Number 3484007
  • Debrecen, Hungary, 4025
    • Investigational Site Number 3484011
  • Debrecen, Hungary, 4032
    • Investigational Site Number 3484005
  • Gyula, Hungary, 5700
    • Investigational Site Number 3484001
  • Nyiregyhaza, Hungary, 4405
    • Investigational Site Number 3484010
  • Nyregyhza, Hungary, 4400
    • Investigational Site Number 3484013
  • Pécs, Hungary, 7623
    • Investigational Site Number 3484004
• Israel
  • Ashkelon, Israel, 7830604
    • Investigational Site Number 3764001
  • Be'Er-Sheva, Israel, 84101
    • Investigational Site Number 3764010
  • Haifa, Israel, 31096
    • Investigational Site Number 3764007
  • Kfar-Saba, Israel, 44281
    • Investigational Site Number 3764009
  • Kfar-Saba, Israel, 44281
    • Investigational Site Number 3764011
  • Nahariya, Israel, 22100
    • Investigational Site Number 3764003
  • Petach Tikva, Israel, 49100
    • Investigational Site Number 3764004
  • Ramat Gan, Israel, 52621
    • Investigational Site Number 3764006
  • Rehovot, Israel, 76100
    • Investigational Site Number 3764005
  • Tel Aviv, Israel, 61480
    • Investigational Site Number 3764002
  • Zefat, Israel, 13100
    • Investigational Site Number 3764008
  • Zerifin, Israel, 70300
    • Investigational Site Number 3764013
• Italy
  • Catania, Italy, 95123
    • Investigational Site Number 3804007
  • Milano, Italy, 20122
    • Investigational Site Number 3804005
  • Milano, Italy, 20132
    • Investigational Site Number 3804004
  • Naples, Italy, 80131
    • Investigational Site Number 3804008
  • Napoli, Italy, 80138
    • Investigational Site Number 3804002
  • Roma, Italy, 00168
    • Investigational Site Number 3804003
  • Siena, Italy, 53100
    • Investigational Site Number 3804006
• Mexico
  • Chihuahua Chihuahua, Mexico, 31217
    • Investigational Site Number 4844009
  • Durango, Durango, Mexico, 34080
    • Investigational Site Number 4844008
  • Guadalajara, Mexico, 44210
    • Investigational Site Number 4844001
  • Guadalajara, Mexico, 44600
    • Investigational Site Number 4844003
  • Merida, Yucatan, Mexico, 97130
    • Investigational Site Number 4844006
  • Monterrey, Mexico, 64460
    • Investigational Site Number 4844005
  • Xalapa, Mexico, 91020
    • Investigational Site Number 4844004
• Poland
  • Białystok, Poland, 15-435
    • Investigational Site Number 6164002
  • Katowice, Poland, 40-081
    • Investigational Site Number 6164006
  • Krakow, Poland, 30-033
    • Investigational Site Number 6164010
  • Krakow, Poland, 30-363
    • Investigational Site Number 6164009
  • Krakow, Poland, 31-209
    • Investigational Site Number 6164004
  • Krakow, Poland, 31-530
    • Investigational Site Number 6164008
  • Lodz, Poland, 92-213
    • Investigational Site Number 6164011
  • Oswiecim, Poland, 32-600
    • Investigational Site Number 6164005
  • Rzeszow, Poland, 35-055
    • Investigational Site Number 6164003
  • Skierniewice, Poland, 96-100
    • Investigational Site Number 6164012
  • Warszawa, Poland, 02-507
    • Investigational Site Number 6164007
• Romania
  • Bacau, Romania, 600154
    • Investigational Site Number 6424002
  • Bacau, Romania, 600238
    • Investigational Site Number 6424001
  • Bucuresti, Romania, 010825
    • Investigational Site Number 6424004
  • Bucuresti, Romania, 013764
    • Investigational Site Number 6424009
  • Bucuresti, Romania, 040172
    • Investigational Site Number 6424010
  • Hunedoara, Romania, 331057
    • Investigational Site Number 6424006
  • Oradea, Romania, 410159
    • Investigational Site Number 6424011
  • Targu-Mures, Romania, 540142
    • Investigational Site Number 6424003
• Russian Federation
  • Chelyabinsk, Russian Federation, 454047
    • Investigational Site Number 6434003
  • Kemerovo, Russian Federation, 650002
    • Investigational Site Number 6434005
  • Krasnodar, Russian Federation, 3500
    • Investigational Site Number 6434002
  • Novosibirsk, Russian Federation, 630091
    • Investigational Site Number 6434004
  • St. Petersburg, Russian Federation, 194358
    • Investigational Site Number 6434001
  • Yaroslavl, Russian Federation, 150003
    • Investigational Site Number 6434006
• South Africa
  • Cape Town, South Africa, 7531
    • Investigational Site Number 7104008
  • Cape Town, South Africa, 7570
    • Investigational Site Number 7104002
  • Johannesburg, South Africa, 1685
    • Investigational Site Number 7104001
  • Johannesburg, South Africa, 2188
    • Investigational Site Number 7104010
  • Johannesburg, South Africa, 2198
    • Investigational Site Number 7104005
  • Pretoria, South Africa, 0002
    • Investigational Site Number 7104006
• Spain
  • Barcelona, Spain, 08035
    • Investigational Site Number 7244011
  • Granada, Spain, 18012
    • Investigational Site Number 7244007
  • Madrid, Spain, 28041
    • Investigational Site Number 7244003
  • Palma De Mallorca, Spain, 07010
    • Investigational Site Number 7244006
  • Sevilla, Spain, 41071
    • Investigational Site Number 7244001
  • Valencia, Spain, 46014
    • Investigational Site Number 7244002
  • Zaragoza, Spain, 50009
    • Investigational Site Number 7244009
• Ukraine
  • Dnipropetrovsk, Ukraine, 49005
    • Investigational Site Number 8044004
  • Kharkiv, Ukraine, 61106
    • Investigational Site Number 8044007
  • Kharkiv, Ukraine, 61166
    • Investigational Site Number 8044010
  • Kiev, Ukraine, 02002
    • Investigational Site Number 8044008
  • Kiev, Ukraine, 04050
    • Investigational Site Number 8044003
  • Kyiv, Ukraine, 02091
    • Investigational Site Number 8044009
  • Kyiv, Ukraine, 03037
    • Investigational Site Number 8044001
  • Kyiv, Ukraine, 03049
    • Investigational Site Number 8044006
  • Lviv, Ukraine, 79010
    • Investigational Site Number 8044005
  • Zaporizhia, Ukraine, 69600
    • Investigational Site Number 8044002
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Investigational Site Number 8404018
    • Guntersville, Alabama, United States, 35976-2206
      • Investigational Site Number 8404045
  • Arizona
    • Phoenix, Arizona, United States, 85018-2701
      • Investigational Site Number 8404004
    • Phoenix, Arizona, United States, 85050-7500
      • Investigational Site Number 8404022
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Investigational Site Number 8404007
  • California
    • Chula Vista, California, United States, 91910
      • Investigational Site Number 8404023
    • Gold River, California, United States, 95670
      • Investigational Site Number 8404044
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 8404011
    • Norco, California, United States, 92860
      • Investigational Site Number 8404003
    • Northridge, California, United States, 91324
      • Investigational Site Number 8404025
    • San Dimas, California, United States, 91713
      • Investigational Site Number 8404038
  • Florida
    • Clearwater, Florida, United States, 33761
      • Investigational Site Number 8404019
    • DeLand, Florida, United States, 32720-0834
      • Investigational Site Number 8404001
    • Ocoee, Florida, United States, 34761-4547
      • Investigational Site Number 8404006
    • Orlando, Florida, United States, 32806
      • Investigational Site Number 8404064
    • Ormond Beach, Florida, United States, 32174-8187
      • Investigational Site Number 8404043
    • Palmetto Bay, Florida, United States, 33157-5503
      • Investigational Site Number 8404013
  • Georgia
    • Savannah, Georgia, United States, 31406
      • Investigational Site Number 8404016
  • Illinois
    • Wauconda, Illinois, United States, 60084-2452
      • Investigational Site Number 8404040
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Investigational Site Number 8404036
    • New Orleans, Louisiana, United States, 70119-6302
      • Investigational Site Number 8404020
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Investigational Site Number 8404014
    • Papillion, Nebraska, United States, 68046-3136
      • Investigational Site Number 8404032
  • New Jersey
    • Hackensack, New Jersey, United States, 07601-1963
      • Investigational Site Number 8404048
  • New York
    • Bronx, New York, United States, 10455
      • Investigational Site Number 8404009
    • New York, New York, United States, 00000
      • Investigational Site Number 8404074
  • North Carolina
    • Wilmington, North Carolina, United States, 28401-6638
      • Investigational Site Number 8404051
    • Winston-Salem, North Carolina, United States, 27103-3914
      • Investigational Site Number 8404028
    • Winston-Salem, North Carolina, United States, 27103-4027
      • Investigational Site Number 8404029
  • Ohio
    • Dayton, Ohio, United States, 45419-4336
      • Investigational Site Number 8404026
  • Pennsylvania
    • Lansdale, Pennsylvania, United States, 19446-1002
      • Investigational Site Number 8404052
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Investigational Site Number 8404031
    • Mount Pleasant, South Carolina, United States, 29464
      • Investigational Site Number 8404021
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Investigational Site Number 8404056
  • Texas
    • Austin, Texas, United States, 78726-4061
      • Investigational Site Number 8404015
    • Austin, Texas, United States, 78731
      • Investigational Site Number 8404050
    • Austin, Texas, United States, 78749
      • Investigational Site Number 8404060
    • Beaumont, Texas, United States, 77702
      • Investigational Site Number 8404005
    • Dallas, Texas, United States, 75208
      • Investigational Site Number 8404035
    • Houston, Texas, United States, 77058
      • Investigational Site Number 8404039
    • Houston, Texas, United States, 77099
      • Investigational Site Number 8404055
    • Hurst, Texas, United States, 76054
      • Investigational Site Number 8404012
    • Lampasas, Texas, United States, 76550-1820
      • Investigational Site Number 8404033
    • McAllen, Texas, United States, 78504
      • Investigational Site Number 8404053
    • Round Rock, Texas, United States, 78681
      • Investigational Site Number 8404057
    • San Antonio, Texas, United States, 78212
      • Investigational Site Number 8404059
    • San Antonio, Texas, United States, 78249-2782
      • Investigational Site Number 8404010
  • Utah
    • Layton, Utah, United States, 84041-1200
      • Investigational Site Number 8404008
  • Washington
    • Renton, Washington, United States, 98057
      • Investigational Site Number 8404042
    • Seattle, Washington, United States, 98105
      • Investigational Site Number 8404041
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53144
      • Investigational Site Number 8404047

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	An ANCOVA model was used for analysis.	Baseline to Week 26
Change From Baseline in SBP for Participants With Baseline SBP ≥130 mmHg at Week 12	An ANCOVA model was used for analysis.	Baseline to Week 12
Change From Baseline in SBP at Week 12 for All Participants	An ANCOVA model was used for analysis.	Baseline to Week 12
Change From Baseline in Body Weight at Week 26	An ANCOVA model was used for analysis.	Baseline to Week 26
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)	An ANCOVA model was used for analysis. No Measure of Dispersion was pre-specified to be calculated.	Baseline to Week 26
Percentage of Participants With HbA1c <6.5% at Week 26		Week 26
Percentage of Participants With HbA1c <7.0% at Week 26		Week 26
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)		Up to 60 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hypoglycemic Events	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].	Up to 60 weeks

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2017
• Primary Completion (Actual): March 25, 2019
• Study Completion (Actual): October 25, 2019

Study Registration Dates

• First Submitted: August 3, 2017
• First Submitted That Met QC Criteria: August 3, 2017
• First Posted (Actual): August 8, 2017

Study Record Updates

• Last Update Posted (Actual): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Diabetes Mellitus; Diabetes Mellitus, Type 2; Kidney Diseases; Renal Insufficiency, Chronic; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
• Other Study ID Numbers: EFC14837; 2016-004889-26; U1111-1187-8662 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No