Efficacy and Safety of Sotagliflozin Versus Placebo in Patients With Type 2 Diabetes Mellitus on Background of Metformin

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Added to Metformin in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin

Primary Objective:

To demonstrate the superiority of Sotagliflozin versus placebo on hemoglobin A1c (HbA1c) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control with metformin.

Secondary Objectives:

• To compare Sotagliflozin versus placebo for.
• Change from baseline in 2-hour postprandial glucose (PPG) following a mixed meal.
• Change from baseline in fasting plasma glucose (FPG).
• Change from Baseline in systolic blood pressure (SBP) for participants with baseline SBP ≥130 millimeter of mercury (mmHg).
• Change from baseline in SBP for all participants.
• Change from baseline in body weight.
• Proportion of participants with HbA1c <6.5% and <7.0%.
• To evaluate the safety of Sotagliflozin versus placebo.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Sotagliflozin (SAR439954); Drug: Metformin; Drug: Placebo

Detailed Description

The duration of the study period is up to 87 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks and a 2 week single blind Run-in phase, a 26 week double-blind Core Treatment Period, a 53-week double-blind Extension Period, a 4 week post treatment Follow-up period to collect safety information.

• Study Type: Interventional
• Enrollment (Actual): 518
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Barrie, Canada, L4M 7G1
    • Investigational Site Number 1242014
  • Brampton, Canada, L6S 0C6
    • Investigational Site Number 1242004
  • Brampton, Canada, L6T 0G1
    • Investigational Site Number 1242005
  • Concord, Canada, L4K 4M2
    • Investigational Site Number 1242001
  • Etobicoke, Canada, M9R 4E1
    • Investigational Site Number 1242007
  • Levis, Canada, G6W 0M5
    • Investigational Site Number 1242010
  • Newmarket, Canada, L3Y 5G8
    • Investigational Site Number 1242012
  • Oakville, Canada, L6M 1M1
    • Investigational Site Number 1242013
  • Pointe Claire, Canada, H9R 4S3
    • Investigational Site Number 1242006
  • Sherbrooke, Canada, J1L 0H8
    • Investigational Site Number 1242008
  • Toronto, Canada, M3M 3E5
    • Investigational Site Number 1242015
  • Toronto, Canada, M4G 3E8
    • Investigational Site Number 1242002
  • Toronto, Canada, M9W 4L6
    • Investigational Site Number 1242003
  • Vancouver, Canada, V5X 0C4
    • Investigational Site Number 1242011
• Hungary
  • Budapest, Hungary, 1033
    • Investigational Site Number 3482002
  • Budapest, Hungary, 1088
    • Investigational Site Number 3482003
  • Budapest, Hungary, 1213
    • Investigational Site Number 3482006
  • Debrecen, Hungary, 4025
    • Investigational Site Number 3482004
  • Esztergom, Hungary, 2500
    • Investigational Site Number 3482001
  • Nyiregyhaza, Hungary, 4400
    • Investigational Site Number 3482007
• Slovakia
  • Bratislava, Slovakia, 851 01
    • Investigational Site Number 7032001
  • Bratislava, Slovakia, 851 01
    • Investigational Site Number 7032005
  • Malacky, Slovakia, 901 01
    • Investigational Site Number 7032003
  • Nitra, Slovakia, 949 11
    • Investigational Site Number 7032002
  • Sturovo, Slovakia, 943 01
    • Investigational Site Number 7032004
  • Trencin, Slovakia, 911 01
    • Investigational Site Number 7032006
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Investigational Site Number 8402003
    • Birmingham, Alabama, United States, 35294
      • Investigational Site Number 8402017
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Investigational Site Number 8402052
  • California
    • Canoga Park, California, United States, 91303
      • Investigational Site Number 8402056
    • Escondido, California, United States, 92025
      • Investigational Site Number 8402020
    • Gold River, California, United States, 95670
      • Investigational Site Number 8402028
    • Greenbrae, California, United States, 94904
      • Investigational Site Number 8402067
    • Huntington Park, California, United States, 90255
      • Investigational Site Number 8402025
    • La Mirada, California, United States, 90638
      • Investigational Site Number 8402051
    • Lemon Grove, California, United States, 91945
      • Investigational Site Number 8402042
    • Lincoln, California, United States, 95648
      • Investigational Site Number 8402011
    • Long Beach, California, United States, 90807
      • Investigational Site Number 8402014
    • Long Beach, California, United States, 90807
      • Investigational Site Number 8402066
    • Los Angeles, California, United States, 90022
      • Investigational Site Number 8402029
    • Los Angeles, California, United States, 90036
      • Investigational Site Number 8402041
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 8402001
    • San Diego, California, United States, 92103
      • Investigational Site Number 8402043
    • San Ramon, California, United States, 94582
      • Investigational Site Number 8402031
    • Tarzana, California, United States, 91356
      • Investigational Site Number 8402047
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Investigational Site Number 8402009
    • Daytona Beach, Florida, United States, 32117
      • Investigational Site Number 8402016
    • Hialeah, Florida, United States, 33012
      • Investigational Site Number 8402006
    • Hialeah, Florida, United States, 33012
      • Investigational Site Number 8402035
    • Hialeah, Florida, United States, 33012
      • Investigational Site Number 8402044
    • Jacksonville, Florida, United States, 32256
      • Investigational Site Number 8402045
    • Miami, Florida, United States, 33126
      • Investigational Site Number 8402026
    • Miami, Florida, United States, 33143
      • Investigational Site Number 8402036
    • Miami, Florida, United States, 33183
      • Investigational Site Number 8402064
    • Miami, Florida, United States, 33185
      • Investigational Site Number 8402007
    • Miami, Florida, United States, 33186
      • Investigational Site Number 8402061
    • Miami Beach, Florida, United States, 33140-3608
      • Investigational Site Number 8402060
    • Opa-locka, Florida, United States, 33054
      • Investigational Site Number 8402033
    • Orlando, Florida, United States, 32825
      • Investigational Site Number 8402039
    • West Palm Beach, Florida, United States, 33406-5854
      • Investigational Site Number 8402063
    • Winter Haven, Florida, United States, 33880
      • Investigational Site Number 8402038
  • Georgia
    • Macon, Georgia, United States, 31210
      • Investigational Site Number 8402008
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Investigational Site Number 8402054
  • Iowa
    • Newton, Iowa, United States, 50208
      • Investigational Site Number 8402069
    • West Des Moines, Iowa, United States, 50265
      • Investigational Site Number 8402022
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Investigational Site Number 8402059
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808-4124
      • Investigational Site Number 8402068
    • Metairie, Louisiana, United States, 70006
      • Investigational Site Number 8402012
    • New Orleans, Louisiana, United States, 70119-6302
      • Investigational Site Number 8402037
    • New Orleans, Louisiana, United States, 70124
      • Investigational Site Number 8402053
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Investigational Site Number 8402021
  • Nebraska
    • Omaha, Nebraska, United States, 68114-3755
      • Investigational Site Number 8402062
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Investigational Site Number 8402005
  • North Carolina
    • Greensboro, North Carolina, United States, 27401
      • Investigational Site Number 8402018
    • Morehead City, North Carolina, United States, 28557
      • Investigational Site Number 8402002
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Investigational Site Number 8402019
  • Oregon
    • Eugene, Oregon, United States, 97404-3233
      • Investigational Site Number 8402015
  • Pennsylvania
    • Lansdale, Pennsylvania, United States, 19446-1002
      • Investigational Site Number 8402058
  • Texas
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 8402030
    • DeSoto, Texas, United States, 75115
      • Investigational Site Number 8402050
    • Fort Worth, Texas, United States, 76164
      • Investigational Site Number 8402010
    • Houston, Texas, United States, 77008
      • Investigational Site Number 8402040
    • Houston, Texas, United States, 77058
      • Investigational Site Number 8402065
    • Houston, Texas, United States, 77079
      • Investigational Site Number 8402057
    • Magnolia, Texas, United States, 77355
      • Investigational Site Number 8402049
    • Odessa, Texas, United States, 79761
      • Investigational Site Number 8402046
    • San Antonio, Texas, United States, 78218
      • Investigational Site Number 8402013
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 8402004
    • Schertz, Texas, United States, 78154
      • Investigational Site Number 8402023
  • Utah
    • Clinton, Utah, United States, 84015
      • Investigational Site Number 8402027
    • Salt Lake City, Utah, United States, 84107
      • Investigational Site Number 8402032
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Investigational Site Number 8402024
  • Washington
    • Seattle, Washington, United States, 98105
      • Investigational Site Number 8402034

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 currently treated with diet and exercise and on metformin at a stable dose ≥1500 milligrams per day (mg/day) for at least 12 weeks. However, participants on metformin at a dose <1500 mg/day at the time of enrollment (stable dose for at least 12 weeks before enrollment) may be eligible for screening if documentation of lack of tolerance of a metformin dose ≥1500 mg/day can be provided.
• Signed written informed consent.

Exclusion criteria:

• Age <18 years at Screening or < legal age of majority, whichever is greater.
• Type 1 diabetes mellitus.
• Body Mass Index (BMI) ≤20 or >45 kilograms per meter square (kg/m^2) at Screening
• Hemoglobin A1c <7% or >10% via central laboratory test at screening.
• Fasting plasma glucose (FPG) >15 millimole per liter (mmol/L) (270 milligrams per deciliter [mg/dL]) measured by the central laboratory at screening (Visit 1) and confirmed by a repeat test (>15 mmol/L [270 mg/dL]) before randomization.
• Women of childbearing potential not willing to use highly effective method(s) of birth control or who are unwilling or unable to be tested for pregnancy during the study.
• Treated with an antidiabetic pharmacological regimen other than metformin ≥1500 mg per day (or maximum tolerated dose) within the 12 weeks preceding the Screening Visit.
• Previous use of any types of insulin for >1 month (at any time, aside from pregnancy for treatment of gestational diabetes).
• History of prior gastric surgical procedure, including gastric banding, within 3 years before the Screening Visit.
• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
• Mean of 3 separate blood pressure measurements >180 mmHg (SBP) or >100 mmHg (diastolic blood pressure [DBP]).
• History of hypertensive urgency or emergency within 12 weeks prior to Screening.
• Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association [NYHA] IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or participants with short life expectancy making implementation of the protocol or interpretation of the study results difficult.
• Aspartate aminotransferase and/or alanine aminotransferase: >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).
• Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
• Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from screening or randomization, whichever is longer.
• Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.
• Participants is unwilling or unable to perform self-monitoring of blood glucose (SMBG), complete the participants diary, or comply with study visits and other study procedures as required per protocol.
• Contraindication to metformin as per local labelling.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sotagliflozin 400 mg + Metformin; Following a 2-week run-in period, sotagliflozin 400 mg was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: tablet. Route of administration: oral.; Drug: Metformin; Pharmaceutical form: tablet. Route of administration: oral.
Placebo Comparator: Placebo + Metformin; Following a 2-week run-in period, matching placebo was administered as 2 tablets, once daily, before the first meal of the day plus metformin as prescribed by the Principal Investigator for up to 26 weeks in the double-blind Core Treatment Period, and participants continued the same treatment in the double-blind Extension Period for up to 53 weeks.	Drug: Metformin; Pharmaceutical form: tablet. Route of administration: oral.; Drug: Placebo; Pharmaceutical form: tablet. Route of administration: oral.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline and Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HbA1c <6.5% at Week 26		Week 26
Percentage of Participants With HbA1c <7.0% at Week 26		Week 26
Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Mixed Meal at Week 26	An ANCOVA model was used for the analysis.	Baseline and Week 26
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	An ANCOVA model was used for the analysis.	Baseline and Week 26
Change From Baseline in Body Weight at Week 26	An ANCOVA model was used for the analysis.	Baseline and Week 26
Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 in Participants With Baseline SBP ≥130 mmHg	An ANCOVA model was used for the analysis.	Baseline and Week 12
Change From Baseline in SBP at Week 12 for All Participants	An ANCOVA model was used for the analysis.	Baseline and Week 12

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]. Participants may be reported in more than one category.	Up to 79 weeks in the treatment period

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2016
• Primary Completion (Actual): February 26, 2019
• Study Completion (Actual): March 22, 2019

Study Registration Dates

• First Submitted: October 5, 2016
• First Submitted That Met QC Criteria: October 5, 2016
• First Posted (Estimate): October 6, 2016

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; Metformin; (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: EFC14834; 2016-001800-49 (EudraCT Number); U1111-1181-6145 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at clinicalstudydatarequest.com. While making information available we continue to protect the privacy of the participants in our clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: clinicalstudydatarequest.com

Drug and device information, study documents

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