Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking Insulin Alone or With Other Oral Antidiabetic Agents (SOTA-INS)

A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Alone or in Addition to Oral Antidiabetes Drugs (OADs)

Primary Objective:

To demonstrate the superiority of sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1C (HbA1c) reduction in participants with type 2 diabetes mellitus (T2D) who have inadequate glycemic control on basal insulin alone or with oral antidiabetes drugs (OADs).

Secondary Objectives:

• To assess the effects of sotagliflozin 400 mg versus placebo on fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), and HbA1c.
• To assess the effects of sotagliflozin 200 mg versus placebo on HbA1c, body weight, FPG, and SBP.
• To evaluate the safety of sotagliflozin 400 and 200 mg versus placebo.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin glargine (HOE901); Drug: Placebo; Drug: Oral Antidiabetes Drugs (OADs); Drug: Sotagliflozin

Detailed Description

Up to 60 weeks (Screening phase of up to 2 weeks, a 4-week Lantus titration/single-blind placebo Run-in phase), a 52-week double blind Treatment Period, and a 2-week post-treatment Follow-up Period.

• Study Type: Interventional
• Enrollment (Actual): 571
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Gabrovo, Bulgaria, 5300
    • Investigational Site Number 1006009
  • Plovdiv, Bulgaria, 4002
    • Investigational Site Number 1006003
  • Ruse, Bulgaria, 7002
    • Investigational Site Number 1006004
  • Ruse, Bulgaria, 7003
    • Investigational Site Number 1006001
  • Smolyan, Bulgaria, 4700
    • Investigational Site Number 1006006
  • Sofia, Bulgaria, 1606
    • Investigational Site Number 1006002
  • Sofia, Bulgaria, 1750
    • Investigational Site Number 1006010
  • Stara Zagora, Bulgaria, 6000
    • Investigational Site Number 1006005
  • Varna, Bulgaria, 9000
    • Investigational Site Number 1006007
• Canada
  • Brampton, Canada, L6S 0C9
    • Investigational Site Number 1246003
  • Burlington, Canada, L7R 1E2
    • Investigational Site Number 1246005
  • Etobicoke, Canada, M9R 4E1
    • Investigational Site Number 1246004
  • Toronto, Canada, M4G 3E8
    • Investigational Site Number 1246002
  • Vancouver, Canada, V5Y 3W2
    • Investigational Site Number 1246001
• Czechia
  • Holesov, Czechia, 769 01
    • Investigational Site Number 2036003
  • Krnov, Czechia, 794 01
    • Investigational Site Number 2036002
  • Olomouc, Czechia, 779 00
    • Investigational Site Number 2036001
  • Ostrava, Czechia, 702 00
    • Investigational Site Number 2036005
  • Praha 10 - Uhrineves, Czechia, 104 00
    • Investigational Site Number 2036006
  • Praha 4, Czechia, 140 46
    • Investigational Site Number 2036007
  • Praha 4, Czechia, 149 00
    • Investigational Site Number 2036008
• France
  • Besançon Cedex, France, 25030
    • Investigational Site Number 2506008
  • Corbeil-Essonnes, France, 91106
    • Investigational Site Number 2506003
  • Dijon, France, 21079
    • Investigational Site Number 2506005
  • Mulhouse, France, 68100
    • Investigational Site Number 2506012
  • Nantes, France, 44093
    • Investigational Site Number 2506004
  • Narbonne, France, 11100
    • Investigational Site Number 2506007
  • Paris, France, 75018
    • Investigational Site Number 2506006
  • Pierre-Benite, France, 69495
    • Investigational Site Number 2506010
  • Poitiers, France, 86021
    • Investigational Site Number 2506009
  • Saint-Mande, France, 94160
    • Investigational Site Number 2506011
  • Vénissieux, France, 69200
    • Investigational Site Number 2506002
• Hungary
  • Budapest, Hungary, 1106
    • Investigational Site Number 3486007
  • Budapest, Hungary, 1134
    • Investigational Site Number 3486002
  • Hatvan, Hungary, 3000
    • Investigational Site Number 3486006
  • Kecskemet, Hungary, 6000
    • Investigational Site Number 3486009
  • Komarom, Hungary, 2900
    • Investigational Site Number 3486003
  • Nyíregyháza, Hungary, 4400
    • Investigational Site Number 3486005
  • Pécs, Hungary, 7623
    • Investigational Site Number 3486001
  • Zalaegerszeg, Hungary, 8900
    • Investigational Site Number 3486008
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Investigational Site Number 7036004
  • Bratislava, Slovakia, 831 06
    • Investigational Site Number 7036008
  • Bratislava, Slovakia, 85101
    • Investigational Site Number 7036001
  • Kosice, Slovakia, 040 01
    • Investigational Site Number 7036010
  • Kosice, Slovakia, 4014
    • Investigational Site Number 7036003
  • Levice, Slovakia, 934 01
    • Investigational Site Number 7036007
  • Levice, Slovakia, 934 05
    • Investigational Site Number 7036009
  • Lucenec, Slovakia, 98401
    • Investigational Site Number 7036011
  • Nitra, Slovakia, 949 11
    • Investigational Site Number 7036006
  • Sabinov, Slovakia, 08301
    • Investigational Site Number 7036005
• United Kingdom
  • Darlington, United Kingdom, DL3 6HX
    • Investigational Site Number 8266002
  • Doncaster, United Kingdom, DN9 2HY
    • Investigational Site Number 8266006
  • Dundee, United Kingdom, DD1 9SY
    • Investigational Site Number 8266008
  • Leicester, United Kingdom, LE5 4PW
    • Investigational Site Number 8266001
  • London, United Kingdom, EC1M 6BQ
    • Investigational Site Number 8266004
  • Salford, United Kingdom, M6 8HD
    • Investigational Site Number 8266003
• United States
  • Arizona
    • Mesa, Arizona, United States, 85213-5226
      • Investigational Site Number 8406028
    • Phoenix, Arizona, United States, 85018
      • Investigational Site Number 8406013
    • Phoenix, Arizona, United States, 85020
      • Investigational Site Number 8406020
  • California
    • Huntington Park, California, United States, 90255
      • Investigational Site Number 8406006
    • Lincoln, California, United States, 95648
      • Investigational Site Number 8406053
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 8406040
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Investigational Site Number 8406043
    • DeLand, Florida, United States, 32720
      • Investigational Site Number 8406008
    • Maitland, Florida, United States, 32751
      • Investigational Site Number 8406030
    • New Port Richey, Florida, United States, 34652
      • Investigational Site Number 8406003
    • North Miami Beach, Florida, United States, 33162
      • Investigational Site Number 8406029
    • Ocoee, Florida, United States, 34761
      • Investigational Site Number 8406052
    • Port Charlotte, Florida, United States, 33952
      • Investigational Site Number 8406001
    • Saint Petersburg, Florida, United States, 33700
      • Investigational Site Number 8406022
    • Tampa, Florida, United States, 33634
      • Investigational Site Number 8406025
    • West Palm Beach, Florida, United States, 33401-3430
      • Investigational Site Number 8406002
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Investigational Site Number 8406054
    • Chicago, Illinois, United States, 60604
      • Investigational Site Number 8406027
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Investigational Site Number 8406042
  • Louisiana
    • New Orleans, Louisiana, United States, 70119-6302
      • Investigational Site Number 8406044
    • New Orleans, Louisiana, United States, 70124
      • Investigational Site Number 8406051
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Investigational Site Number 8406024
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Investigational Site Number 8406016
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Investigational Site Number 8406011
  • Nebraska
    • Papillion, Nebraska, United States, 68046-3136
      • Investigational Site Number 8406010
  • New York
    • New York, New York, United States, 10016-6023
      • Investigational Site Number 8406018
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Investigational Site Number 8406034
    • Chapel Hill, North Carolina, United States, 27517
      • Investigational Site Number 8406046
    • Charlotte, North Carolina, United States, 28209
      • Investigational Site Number 8406026
    • Greenville, North Carolina, United States, 27834
      • Investigational Site Number 8406038
    • Hickory, North Carolina, United States, 28601
      • Investigational Site Number 8406036
    • Wilmington, North Carolina, United States, 28401-6638
      • Investigational Site Number 8406015
    • Winston-Salem, North Carolina, United States, 27103
      • Investigational Site Number 8406019
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • Investigational Site Number 8406031
    • Columbus, Ohio, United States, 43201
      • Investigational Site Number 8406023
    • Dublin, Ohio, United States, 43016
      • Investigational Site Number 8406005
    • Mentor, Ohio, United States, 44060
      • Investigational Site Number 8406004
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73111
      • Investigational Site Number 8406033
  • South Carolina
    • Moncks Corner, South Carolina, United States, 29461-5017
      • Investigational Site Number 8406032
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Investigational Site Number 8406009
    • Seymour, Tennessee, United States, 37865-5270
      • Investigational Site Number 8406045
  • Texas
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 8406047
    • Dallas, Texas, United States, 75231
      • Investigational Site Number 8406017
    • Houston, Texas, United States, 77079
      • Investigational Site Number 8406048
    • Houston, Texas, United States, 77099
      • Investigational Site Number 8406037
    • McAllen, Texas, United States, 78504
      • Investigational Site Number 8406039
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 8406050
    • Shavano Park, Texas, United States, 78231
      • Investigational Site Number 8406021
  • Utah
    • Salt Lake City, Utah, United States, 84102-1553
      • Investigational Site Number 8406035
    • West Jordan, Utah, United States, 84088-8865
      • Investigational Site Number 8406014

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 Mellitus (T2DM) using any types of basal insulin alone or in combination with up to 2 OADs.
• Participants have given written informed consent to participate in the study in accordance with local regulations.

Exclusion criteria:

• At the time of Screening age <18 years or <legal age of majority, whichever is greater.
• Type 1 diabetes mellitus.
• Oral antidiabetic drugs dose not stable for 8 weeks before Screening.
• Use of basal insulin therapy (e.g., insulin glargine, Neutral Protamine Hagedorn (NPH), detemir, or degludec) for less than 6 months before Screening.
• Dose of basal insulin (e.g., insulin glargine, NPH, detemir, or degludec) not stable for 8 weeks before Screening (i.e., total daily insulin dose increased or decreased by more than 20%).
• Known unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema that is likely to require laser, surgical treatment during study period.
• Use of injectable diabetes drugs other than basal insulin (e.g., insulin glargine, NPH, detemir, or degludec), i.e., prandial or rapid-acting insulins, short-acting insulins, glucagon-like peptide 1 (GLP-1) receptor agonists, or inhaled prandial insulin (Afrezza) within 8 weeks of Screening.
• Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the trial.
• Use of systemic glucocorticoids (excluding topical, intra articular, or ophthalmic application, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
• 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 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.
• Known presence of factors that interfere with the Central Lab HbA1c measurement (e.g., genetic hemoglobin (Hb) variants) compromising the reliability of HbA1c assessment or medical conditions that affect interpretation of HbA1c results (e.g., blood transfusion or severe blood loss in the last 3 months prior to randomization, any condition that shortens erythrocyte survival).
• Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from prior to Screening, whichever is longer.
• Participants unwilling to perform self-monitoring of blood glucose (SMBG), complete the patient diary, or comply with study visits and other study procedures as required per protocol.
• HbA1c <7.5% or HbA1c >10.5% measured by the central laboratory at Screening.
• HbA1c <7% measured by the central laboratory at Visit 5 (Week -1).
• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
• Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.
• Women of childbearing potential 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.
• Mean of 3 separate blood pressure measurements >180 mmHg (systolic blood pressure [SBP]) or >100 mmHg (diastolic blood pressure [DBP]).
• History of gastric surgery including history of gastric banding or inflammatory bowel disease within 3 years prior to the Screening Visit.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of the normal laboratory range
• Total bilirubin >1.5 times the upper limit of the normal laboratory range (except in case of Gilbert's syndrome).

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: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Following a 4-week run-in period, participants were randomized to matching placebo to sotagliflozin 200 milligrams (mg) administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Drug: Insulin glargine (HOE901); Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: Lantus; Drug: Placebo; Pharmaceutical form: Tablet Route of administration: Oral; Drug: Oral Antidiabetes Drugs (OADs); OADs (including metformin) as prescribed by the investigator as per local labeling.
Experimental: Sotagliflozin 200 mg; Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Drug: Insulin glargine (HOE901); Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: Lantus; Drug: Placebo; Pharmaceutical form: Tablet Route of administration: Oral; Drug: Oral Antidiabetes Drugs (OADs); OADs (including metformin) as prescribed by the investigator as per local labeling.; Drug: Sotagliflozin; Pharmaceutical form: Tablet Route of administration: Oral; Other Names: SAR439954
Experimental: Sotagliflozin 400 mg; Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.	Drug: Insulin glargine (HOE901); Pharmaceutical form: Solution Route of administration: Subcutaneous; Other Names: Lantus; Drug: Oral Antidiabetes Drugs (OADs); OADs (including metformin) as prescribed by the investigator as per local labeling.; Drug: Sotagliflozin; Pharmaceutical form: Tablet 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 Hemoglobin A1c (HbA1c) at Week 18	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline and Week 18

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in SBP at Week 12 for All Participants	An ANCOVA model was used for the analysis.	Baseline to Week 12
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18	FPG was performed in fasting state, that is, without any food intake (except for water) for at least 8 hours. An ANCOVA model was used for the analysis.	Baseline and Week 18
Change From Baseline in Body Weight at Week 18	An ANCOVA model was used for the analysis.	Baseline and Week 18
Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12	An ANCOVA model was used for the analysis. Here, N is the number of participants with data available at a given time point.	Baseline and Week 12
Change From Baseline in HbA1c at Week 52	An ANCOVA model was used for the analysis.	Baseline and Week 52
Change From Baseline in Body Weight at Week 52	An ANCOVA model was used for the analysis.	Baseline and Week 52
Percentage of Participants With Adverse Events (AEs)	An 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 this treatment.	First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 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 55.7 weeks

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2017
• Primary Completion (Actual): September 17, 2019
• Study Completion (Actual): September 27, 2019

Study Registration Dates

• First Submitted: September 14, 2017
• First Submitted That Met QC Criteria: September 14, 2017
• First Posted (Actual): September 18, 2017

Study Record Updates

• Last Update Posted (Actual): May 11, 2021
• Last Update Submitted That Met QC Criteria: April 16, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Insulin Glargine; (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: EFC14868; 2016-001804-43 (EudraCT Number); U1111-1190-7567 (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
• product manufactured in and exported from the U.S.: Yes