Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus on Background of Sulfonylurea Alone or With Metformin

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

Primary Objective:

To demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo on Hemoglobin A1c (HbA1c) reduction at Week 26 in participant with type 2 diabetes (T2D) who have inadequate glycemic control with a Sulfonylurea alone or in combination with Metformin.

Secondary Objectives:

• To compare Sotagliflozin 400 mg versus placebo based on:
• 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 (mm Hg).
• Change from baseline in SBP for all participants.
• Change from baseline in body weight.
• Percentage of participants with HbA1c <6.5% and <7.0%.
• To evaluate the safety of Sotagliflozin 400 mg versus placebo throughout the 79-week trial.

Study Overview

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

Detailed Description

The duration per participants is up to 85 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, and a 2-week post treatment Follow-up period to collect safety information.

• Study Type: Interventional
• Enrollment (Actual): 507
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Investigational Site Number 1003003
  • Ruse, Bulgaria, 7002
    • Investigational Site Number 1003002
  • Sofia, Bulgaria, 1784
    • Investigational Site Number 1003004
• Estonia
  • Parnu, Estonia, 8001
    • Investigational Site Number 2333003
• Hungary
  • Balatonfüred, Hungary, 8230
    • Investigational Site Number 3483001
  • Budapest, Hungary, 1033
    • Investigational Site Number 3483007
  • Budapest, Hungary, 1036
    • Investigational Site Number 3483008
  • Budapest, Hungary, 1036
    • Investigational Site Number 3483010
  • Budapest, Hungary, 1106
    • Investigational Site Number 3483004
  • Budapest, Hungary, 1213
    • Investigational Site Number 3483006
  • Gyula, Hungary, 5700
    • Investigational Site Number 3483011
  • Hatvan, Hungary, 3000
    • Investigational Site Number 3483009
  • Kecskemet, Hungary, 6000
    • Investigational Site Number 3483005
  • Pécs, Hungary, 7623
    • Investigational Site Number 3483003
  • Zalaegerszeg, Hungary, 8900
    • Investigational Site Number 3483012
• Korea, Republic of
  • Goyang-Si, Gyeonggi-Do, Korea, Republic of, 10380
    • Investigational Site Number 4103001
  • Guri-Si, Gyeonggi-Do, Korea, Republic of, 11923
    • Investigational Site Number 4103011
  • Seongnam-Si, Gyeonggi-Do, Korea, Republic of, 13620
    • Investigational Site Number 4103003
  • Seoul, Korea, Republic of, 06591
    • Investigational Site Number 4103007
  • Seoul, Korea, Republic of, 1830
    • Investigational Site Number 4103006
  • Seoul, Korea, Republic of, 3722
    • Investigational Site Number 4103010
  • Seoul, Korea, Republic of, 7345
    • Investigational Site Number 4103005
  • Wonju-Si, Gangwon-Do, Korea, Republic of, 26426
    • Investigational Site Number 4103009
• Poland
  • Gdansk, Poland, 80-382
    • Investigational Site Number 6163005
  • Gdynia, Poland, 81-537
    • Investigational Site Number 6163006
  • Katowice, Poland, 40-040
    • Investigational Site Number 6163003
  • Poznan, Poland, 60702
    • Investigational Site Number 6163002
  • Warszawa, Poland, 01-192
    • Investigational Site Number 6163001
  • Wroclaw, Poland, 50-381
    • Investigational Site Number 6163004
• Romania
  • Bucuresti, Romania
    • Investigational Site Number 6423004
  • Iasi, Romania, 700732
    • Investigational Site Number 6423002
• Slovakia
  • Bratislava, Slovakia, 831 06
    • Investigational Site Number 7033006
  • Bratislava, Slovakia, 851 01
    • Investigational Site Number 7033001
  • Bratislava, Slovakia, 851 01
    • Investigational Site Number 7033002
  • Malacky, Slovakia, 901 01
    • Investigational Site Number 7033004
  • Sturovo, Slovakia, 943 01
    • Investigational Site Number 7033003
  • Trencin, Slovakia, 911 01
    • Investigational Site Number 7033007
• Ukraine
  • Kyiv, Ukraine, 2002
    • Investigational Site Number 8043001
  • Kyiv, Ukraine, 3037
    • Investigational Site Number 8043003
  • Kyiv, Ukraine, 3049
    • Investigational Site Number 8043002
• United Kingdom
  • Birmingham, United Kingdom, B15 2SQ
    • Investigational Site Number 8263012
  • Cardiff, United Kingdom, CF15 9SS
    • Investigational Site Number 8263009
  • Glasgow, United Kingdom, G20 0SP
    • Investigational Site Number 8263007
  • Hexham, United Kingdom, NE46 1QJ
    • Investigational Site Number 8263008
  • Inverness, United Kingdom, IV2 3JH
    • Investigational Site Number 8263003
  • Liverpool, United Kingdom, L22 0LG
    • Investigational Site Number 8263014
  • Manchester, United Kingdom, M15 6SE
    • Investigational Site Number 8263011
  • Reading, United Kingdom, RG2 0TG
    • Investigational Site Number 8263010
• United States
  • Arizona
    • Litchfield Park, Arizona, United States, 85340
      • Investigational Site Number 8403003
    • Peoria, Arizona, United States, 85381
      • Investigational Site Number 8403018
  • California
    • Greenbrae, California, United States, 94904
      • Investigational Site Number 8403009
    • Huntington Park, California, United States, 90255
      • Investigational Site Number 8403012
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 8403019
    • Montclair, California, United States, 91763
      • Investigational Site Number 8403034
    • Spring Valley, California, United States, 91978
      • Investigational Site Number 8403016
    • Tustin, California, United States, 92780
      • Investigational Site Number 8403014
  • Colorado
    • Northglenn, Colorado, United States, 80234
      • Investigational Site Number 8403001
  • Florida
    • Bradenton, Florida, United States, 34201
      • Investigational Site Number 8403029
    • New Port Richey, Florida, United States, 34652
      • Investigational Site Number 8403004
    • North Miami Beach, Florida, United States, 33162
      • Investigational Site Number 8403020
    • Ocoee, Florida, United States, 34761
      • Investigational Site Number 8403026
    • Orlando, Florida, United States, 32810
      • Investigational Site Number 8403032
    • Palm Harbor, Florida, United States, 34684
      • Investigational Site Number 8403008
    • Pembroke Pines, Florida, United States, 33026
      • Investigational Site Number 8403006
    • Port Charlotte, Florida, United States, 33952
      • Investigational Site Number 8403013
  • Idaho
    • Nampa, Idaho, United States, 83686
      • Investigational Site Number 8403007
  • Michigan
    • Flint, Michigan, United States, 48532
      • Investigational Site Number 8403011
  • Minnesota
    • Richfield, Minnesota, United States, 55432
      • Investigational Site Number 8403025
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Investigational Site Number 8403021
  • North Carolina
    • Greensboro, North Carolina, United States, 27408
      • Investigational Site Number 8403028
    • Shelby, North Carolina, United States, 28150
      • Investigational Site Number 8403015
  • Pennsylvania
    • Hatboro, Pennsylvania, United States, 19040
      • Investigational Site Number 8403033
  • Tennessee
    • Kingsport, Tennessee, United States, 37660
      • Investigational Site Number 8403030
  • Texas
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 8403002
    • Houston, Texas, United States, 77081
      • Investigational Site Number 8403022
  • Virginia
    • Burke, Virginia, United States, 22015
      • Investigational Site Number 8403005

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 T2D treated with a Sulfonylurea (≥half the maximum recommended dose as per local label or maximum tolerated dose [documented]) as monotherapy or in combination with Metformin (≥1500 mg per day or maximum tolerated dose [documented]) each at a stable dose for at least 12 weeks without a dose adjustment before screening.
• Signed written informed consent.

Exclusion criteria:

• At the time of screening, age <18 years or < legal age of majority, whichever is greater.
• Body Mass Index (BMI) ≤20 or >45 kilograms per meter square (kg/m^2) at Screening.
• Hemoglobin A1c (HbA1c) <7% or HbA1c >10% via central lab test at screening.
• Fasting plasma glucose (FPG) >15 mmol/L (270 mg/dL) measured by the central laboratory at screening (Visit 1), and confirmed (>15 mmol/L [270 mg/dL]) by a repeat test before randomization.
• Women of childbearing potential with no effective contraceptive method.
• Treated with an antidiabetic pharmacological regimen other than a Sulfonylurea at a stable dose with or without Metformin within 12 weeks preceding the screening visit.
• Previous insulin use >1 month (at any time, aside from treatment of gestational diabetes).
• History of prior gastric surgical procedure including gastric banding or inflammatory bowel disease within 3 years before the Screening Visit.
• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
• History of severe hypoglycemia within 6 months prior to the Screening visit.
• Systolic blood pressure (SBP) >180 millimeter per mercury (mmHg) or diastolic blood pressure (DBP) >100 mmHg or history of hypertensive emergency.
• Aspartate aminotransferase and/or alanine aminotransferase: >3 times the upper limit of the normal laboratory range (ULN).
• Total bilirubin: >1.5 times ULN (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.
• Pregnancy, breastfeeding.
• Participants is unwilling to perform self-monitoring of blood glucose (SMBG), and complete the participant's diary as required per protocol.

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
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sotagliflozin 400 mg; Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Drug: Sotagliflozin (SAR439954); Pharmaceutical form: tablet Route of administration: oral
PLACEBO_COMPARATOR: Placebo; Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 79 weeks.	Drug: Metformin; Pharmaceutical form: tablet Route of administration: oral; Drug: Placebo; Pharmaceutical form: tablet Route of administration: oral; Drug: Sulfonylurea; 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	Missing data are imputed using the retrieved dropouts imputation method. An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline to 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 Fasting Plasma Glucose (FPG) at Week 26	Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.	Baseline to Week 26
Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg	Missing data are imputed using the washout imputation method under the missing, not at random framework. An ANCOVA model was used for the analysis.	Baseline to Week 12
Change From Baseline in SBP at Week 12 for All Participants	Missing data are imputed using washout imputation method under the missing not at random framework. An ANCOVA model was used for the analysis.	Baseline to Week 12
Change From Baseline in Body Weight at Week 26	Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.	Baseline to Week 26

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): February 24, 2017
• Primary Completion (ACTUAL): April 17, 2019
• Study Completion (ACTUAL): April 30, 2019

Study Registration Dates

• First Submitted: February 24, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (ACTUAL): February 28, 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; 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: EFC14835; 2016-002826-35 (EUDRACT_NUMBER); U1111-1186-2612 (OTHER: 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 Sanofi continues to protect the privacy of the participants in 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