Efficacy and Bone Safety of Sotagliflozin 400 and 200 mg Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control (SOTA-BONE)

A 26-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Study With a 78-week Extension Period to Evaluate the Efficacy and Bone Safety of Sotagliflozin in Patients 55 Years or Older With Type 2 Diabetes Mellitus and Inadequate Glycemic Control

The primary objective is to demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1c (Hb1Ac) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise only or with a stable antidiabetes regimen.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Sotagliflozin

Detailed Description

Study duration per participant is approximately 110 weeks (Screening period of up to 2 weeks, 2 week single-blind run-in period), a 26-week double-blind core treatment period, a 78-week double-blind extension period, and a 2- week post treatment follow up period.

Dual-energy X-ray absorptiometry (DXA) scans will be performed to assess Bone Mineral Density and Fat vs. Lean body mass at baseline and Weeks 26, 52, and 104.

• Study Type: Interventional
• Enrollment (Actual): 376
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Fremantle, Australia, 6160
    • Investigational Site Number 0369003
  • Merewether, Australia, 2291
    • Investigational Site Number 0369002
  • Parkville, Australia, 3050
    • Investigational Site Number 0369004
• Canada
  • Brampton, Canada, L6S 0C6
    • Investigational Site Number 1249003
  • Etobicoke, Canada, M9R 4E1
    • Investigational Site Number 1249008
  • Pointe-Claire, Canada, H9R 4S3
    • Investigational Site Number 1249005
  • Thornhill, Canada, L4J 1W3
    • Investigational Site Number 1249006
  • Thornhill, Canada, L4J 8L7
    • Investigational Site Number 1249004
  • Vancouver, Canada, V5Y 3W2
    • Investigational Site Number 1249007
  • Victoriaville, Canada, G6P 6P6
    • Investigational Site Number 1249002
• Korea, Republic of
  • Daejeon, Korea, Republic of, 35233
    • Investigational Site Number 4109006
  • Guri-Si, Gyeonggi-Do, Korea, Republic of, 11923
    • Investigational Site Number 4109005
  • Gyeonggi-Do, Korea, Republic of, 13620
    • Investigational Site Number 4109003
  • Seoul, Korea, Republic of, 03722
    • Investigational Site Number 4109004
  • Seoul, Korea, Republic of, 1830
    • Investigational Site Number 4109001
• Mexico
  • Aguascalientes, Mexico, 20129
    • Investigational Site Number 4849001
  • Aguascalientes, Aguascalientes, Mexico, 20230
    • Investigational Site Number 4849006
  • Cuernavaca, Mexico, 62250
    • Investigational Site Number 4849003
  • Guadalajara Jalisco, Mexico, 44130
    • Investigational Site Number 4849002
  • Monterrey, Mexico, 64460
    • Investigational Site Number 4849004
  • Xalapa, Mexico, 91020
    • Investigational Site Number 4849005
• New Zealand
  • Auckland, New Zealand, 1309
    • Investigational Site Number 5549004
  • Christchurch, New Zealand, 8011
    • Investigational Site Number 5549003
  • Rotorua, New Zealand, 3010
    • Investigational Site Number 5549001
  • Wellington, New Zealand, 6021
    • Investigational Site Number 5549002
• Russian Federation
  • Kemerovo, Russian Federation, 650002
    • Investigational Site Number 6439007
  • Novosibirsk, Russian Federation, 630091
    • Investigational Site Number 6439005
  • Saint-Petersburg, Russian Federation, 195213
    • Investigational Site Number 6439002
  • Saint-Petersburg, Russian Federation, 196601
    • Investigational Site Number 6439003
  • St. Petersburg, Russian Federation, 194358
    • Investigational Site Number 6439001
  • Yaroslavl, Russian Federation, 150003
    • Investigational Site Number 6439006
• Taiwan
  • Changhua, Taiwan, 500
    • Investigational Site Number 1589005
  • New Taipei City, Taiwan, 220
    • Investigational Site Number 1589008
  • Taichung, Taiwan, 402
    • Investigational Site Number 1589006
  • Taichung, Taiwan, 43303
    • Investigational Site Number 1589007
  • Tainan, Taiwan, 710
    • Investigational Site Number 1589001
  • Tainan, Taiwan
    • Investigational Site Number 1589002
  • Taipei, Taiwan, 100
    • Investigational Site Number 1589004
  • Taipei, Taiwan, 11217
    • Investigational Site Number 1589003
• United States
  • California
    • Escondido, California, United States, 92025
      • Investigational Site Number 8409009
    • Greenbrae, California, United States, 94904
      • Investigational Site Number 8409010
    • Walnut Creek, California, United States, 94598
      • Investigational Site Number 8409005
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Investigational Site Number 8409012
  • Indiana
    • Evansville, Indiana, United States, 47714-8011
      • Investigational Site Number 8409011
  • Kansas
    • Wichita, Kansas, United States, 67205-1138
      • Investigational Site Number 8409014
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Investigational Site Number 8409015
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • Investigational Site Number 8409002
    • Wilmington, North Carolina, United States, 28401-6638
      • Investigational Site Number 8409001
  • Ohio
    • Dayton, Ohio, United States, 45419-4336
      • Investigational Site Number 8409008
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Investigational Site Number 8409004
  • Texas
    • Austin, Texas, United States, 78749
      • Investigational Site Number 8409013
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 8409003
    • Katy, Texas, United States, 77450
      • Investigational Site Number 8409007

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Participants with T2D managed with diet and exercise only or with a stable antidiabetes regimen (in monotherapy or combination therapy that can include oral antidiabetes medications, insulin, or glucagon-like peptide-1 agonists) for more than 12 weeks.
• Participants has given written informed consent to participate in the study in accordance with local regulations.

Exclusion criteria:

• Age <55 years.
• Women who have been postmenopausal (or undergone bilateral oophorectomy) for less than 5 years.
• Type 1 diabetes mellitus.
• Body mass index (BMI) ≤20 or >45 kilogram per meter square kg/m^2 or bodyweight that exceeds the weight limits of the DXA scanner.
• Hemoglobin A1C (HbA1c) <7.0% or HbA1c >11.0%.
• Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor or thiazolidinedione within 24 months.
• Bone mineral density (BMD) T- score <-2.0 at any site (ie, lumbar spine, total hip, or femoral neck).
• History of fracture within 12 months (except for fractures of the hand/fingers, foot/toes, facial bones, and skull).
• Treatment with medications known to affect bone mass or modify the risk of fractures within 36 months (eg, bisphosphonates, selective estrogen receptor modulators, calcitonin, teriparatide, denosumab, strontium ranelate, growth hormone, aromatase inhibitors, androgen deprivation therapy, carbamazepine, phenytoin, and phenobarbital). Use of hormonal replacement that includes systemic or transdermal estrogen or testosterone is excluded unless is stable for at least 24 months prior to Screening.
• Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at randomization.
• Uncontrolled high blood pressure, severe anemia, severe cardiovascular problems, such as heart failure, active cancer, or other conditions that the Investigator believes with result in a short life expectancy.
• Renal disease as defined by an estimated glomerular filtration rate (eGFR) <30 milliliter per minute (mL/min)/1.73 meter square (m^2) at the Screening Visit by the 4 variable Modification of Diet in Renal Disease equation.

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: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, 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 106 weeks.	Drug: Placebo; Pharmaceutical form: Tablet; Route of administration: Oral
EXPERIMENTAL: Sotagliflozin 200 mg; Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, 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 104 weeks.	Drug: Placebo; Pharmaceutical form: Tablet; Route of administration: Oral; Drug: Sotagliflozin; Pharmaceutical form: Tablet; Route of administration: Oral; Other Names: SAR439954
EXPERIMENTAL: Sotagliflozin 400 mg; Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, 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 104 weeks.	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 26	An analysis of covariance (ANCOVA) model is used for analysis.	Baseline to Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Week 26	An ANCOVA model is used for analysis.	Baseline to Week 26
Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Week 26	An ANCOVA model is used for analysis.	Baseline to Week 26
Percent Change From Baseline in Bone Mineral Density (BMD) of Femoral Neck at Week 26	An ANCOVA model is used for analysis.	Baseline to Week 26
Change From Baseline in Body Weight at Week 26	An ANCOVA model is used for analysis.	Baseline to Week 26
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	An ANCOVA model is used for analysis.	Baseline to Week 26
Change From Baseline in Systolic Blood Pressure (SBP) at Week 12	An ANCOVA model is used for analysis.	Baseline to Week 12
Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% at Week 26		Week 26
Percentage of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.	up to 106 weeks

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Collaborators: Sanofi

Study record dates

Study Major Dates

• Study Start (ACTUAL): February 19, 2018
• Primary Completion (ACTUAL): May 22, 2019
• Study Completion (ACTUAL): May 30, 2020

Study Registration Dates

• First Submitted: December 21, 2017
• First Submitted That Met QC Criteria: December 21, 2017
• First Posted (ACTUAL): December 29, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 25, 2021
• Last Update Submitted That Met QC Criteria: June 3, 2021
• Last Verified: June 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; (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: EFC15294; 2017-002041-30; U1111-1195-6371 (OTHER: 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.: No