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

NCT03386344 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC152942017-002041-30U1111-1195-6371
• Study Type: interventional
• Target: 376
• Locations: 8 countries
• Sites: 53

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Week 26

  Baseline to Week 26

• Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Week 26

  Baseline to Week 26

• Percent Change From Baseline in Bone Mineral Density (BMD) of Femoral Neck at Week 26

  Baseline to Week 26

• Change From Baseline in Body Weight at Week 26

  Baseline to Week 26

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

  Baseline to Week 26

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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

Sotagliflozin 200 mg

EXPERIMENTAL

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: Sotagliflozin; Drug: Placebo

Sotagliflozin 400 mg

EXPERIMENTAL

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

Interventions

Sotagliflozin DRUG

Pharmaceutical form: Tablet; Route of administration: Oral

Also known as: SAR439954

Sotagliflozin 200 mg; Sotagliflozin 400 mg

Placebo DRUG

Pharmaceutical form: Tablet; Route of administration: Oral

Placebo; Sotagliflozin 200 mg

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (53)

Investigational Site Number 8409009

Escondido, California, 92025, United States

Location

Investigational Site Number 8409010

Greenbrae, California, 94904, United States

Location

Investigational Site Number 8409005

Walnut Creek, California, 94598, United States

Location

Investigational Site Number 8409012

Columbus, Georgia, 31904, United States

Location

Investigational Site Number 8409011

Evansville, Indiana, 47714-8011, United States

Location

Investigational Site Number 8409014

Wichita, Kansas, 67205-1138, United States

Location

Investigational Site Number 8409015

Albuquerque, New Mexico, 87106, United States

Location

Investigational Site Number 8409002

Chapel Hill, North Carolina, 27517, United States

Location

Investigational Site Number 8409001

Wilmington, North Carolina, 28401-6638, United States

Location

Investigational Site Number 8409008

Dayton, Ohio, 45419-4336, United States

Location

Investigational Site Number 8409004

Chattanooga, Tennessee, 37404, United States

Location

Investigational Site Number 8409013

Austin, Texas, 78749, United States

Location

Investigational Site Number 8409003

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8409007

Katy, Texas, 77450, United States

Location

Investigational Site Number 0369003

Fremantle, 6160, Australia

Location

Investigational Site Number 0369002

Merewether, 2291, Australia

Location

Investigational Site Number 0369004

Parkville, 3050, Australia

Location

Investigational Site Number 1249003

Brampton, L6S 0C6, Canada

Location

Investigational Site Number 1249008

Etobicoke, M9R 4E1, Canada

Location

Investigational Site Number 1249005

Pointe-Claire, H9R 4S3, Canada

Location

Investigational Site Number 1249006

Thornhill, L4J 1W3, Canada

Location

Investigational Site Number 1249004

Thornhill, L4J 8L7, Canada

Location

Investigational Site Number 1249007

Vancouver, V5Y 3W2, Canada

Location

Investigational Site Number 1249002

Victoriaville, G6P 6P6, Canada

Location

Investigational Site Number 4849001

Aguascalientes, 20129, Mexico

Location

Investigational Site Number 4849006

Aguascalientes, Aguascalientes, 20230, Mexico

Location

Investigational Site Number 4849003

Cuernavaca, 62250, Mexico

Location

Investigational Site Number 4849002

Guadalajara Jalisco, 44130, Mexico

Location

Investigational Site Number 4849004

Monterrey, 64460, Mexico

Location

Investigational Site Number 4849005

Xalapa, 91020, Mexico

Location

Investigational Site Number 5549004

Auckland, 1309, New Zealand

Location

Investigational Site Number 5549003

Christchurch, 8011, New Zealand

Location

Investigational Site Number 5549001

Rotorua, 3010, New Zealand

Location

Investigational Site Number 5549002

Wellington, 6021, New Zealand

Location

Investigational Site Number 6439007

Kemerovo, 650002, Russia

Location

Investigational Site Number 6439005

Novosibirsk, 630091, Russia

Location

Investigational Site Number 6439001

Saint Petersburg, 194358, Russia

Location

Investigational Site Number 6439002

Saint Petersburg, 195213, Russia

Location

Investigational Site Number 6439003

Saint Petersburg, 196601, Russia

Location

Investigational Site Number 6439006

Yaroslavl, 150003, Russia

Location

Investigational Site Number 4109006

Daejeon, 35233, South Korea

Location

Investigational Site Number 4109005

Guri-Si, Gyeonggi-Do, 11923, South Korea

Location

Investigational Site Number 4109003

Gyeonggi-do, 13620, South Korea

Location

Investigational Site Number 4109004

Seoul, 03722, South Korea

Location

Investigational Site Number 4109001

Seoul, 1830, South Korea

Location

Investigational Site Number 1589005

Changhua, 500, Taiwan

Location

Investigational Site Number 1589008

New Taipei City, 220, Taiwan

Location

Investigational Site Number 1589006

Taichung, 402, Taiwan

Location

Investigational Site Number 1589007

Taichung, 43303, Taiwan

Location

Investigational Site Number 1589001

Tainan, 710, Taiwan

Location

Investigational Site Number 1589002

Tainan, Taiwan

Location

Investigational Site Number 1589004

Taipei, 100, Taiwan

Location

Investigational Site Number 1589003

Taipei, 11217, Taiwan

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Medical Affairs
• Organization: Lexicon Pharmaceuticals, Inc.

medical-information@lexpharma.com

(510) 338-6064

Study Officials

• Suman Wason, MD

  Lexicon Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2017
• First Posted: December 29, 2017
• Study Start: February 19, 2018
• Primary Completion: May 22, 2019
• Study Completion: May 30, 2020
• Last Updated: June 25, 2021
• Results First Posted: June 25, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5); AU (3); ME (6); TW (8); NZ (4); US (14); RU (6); CA (7)