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

NCT ID: NCT03386344

Last Updated: 2021-06-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 376 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-19
• Study Completion Date: 2020-05-30

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.

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.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: Tablet; Route of administration: Oral

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.

Group Type: EXPERIMENTAL

Sotagliflozin

Intervention Type: DRUG

Pharmaceutical form: Tablet; Route of administration: Oral

Placebo

Intervention Type: DRUG

Pharmaceutical form: Tablet; Route of administration: Oral

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.

Group Type: EXPERIMENTAL

Sotagliflozin

Intervention Type: DRUG

Pharmaceutical form: Tablet; Route of administration: Oral

Interventions

Sotagliflozin

Pharmaceutical form: Tablet; Route of administration: Oral

Intervention Type: DRUG

Placebo

Pharmaceutical form: Tablet; Route of administration: Oral

Intervention Type: DRUG

Other Intervention Names

SAR439954

Eligibility Criteria

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.

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Lexicon Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suman Wason, MD

Role: STUDY_DIRECTOR

Lexicon Pharmaceuticals, Inc.

Locations

Investigational Site Number 8409009

Escondido, California, United States

Investigational Site Number 8409010

Greenbrae, California, United States

Investigational Site Number 8409005

Walnut Creek, California, United States

Investigational Site Number 8409012

Columbus, Georgia, United States

Investigational Site Number 8409011

Evansville, Indiana, United States

Investigational Site Number 8409014

Wichita, Kansas, United States

Investigational Site Number 8409015

Albuquerque, New Mexico, United States

Investigational Site Number 8409002

Chapel Hill, North Carolina, United States

Investigational Site Number 8409001

Wilmington, North Carolina, United States

Investigational Site Number 8409008

Dayton, Ohio, United States

Investigational Site Number 8409004

Chattanooga, Tennessee, United States

Investigational Site Number 8409013

Austin, Texas, United States

Investigational Site Number 8409003

Dallas, Texas, United States

Investigational Site Number 8409007

Katy, Texas, United States

Investigational Site Number 0369003

Fremantle, , Australia

Investigational Site Number 0369002

Merewether, , Australia

Investigational Site Number 0369004

Parkville, , Australia

Investigational Site Number 1249003

Brampton, , Canada

Investigational Site Number 1249008

Etobicoke, , Canada

Investigational Site Number 1249005

Pointe-Claire, , Canada

Investigational Site Number 1249006

Thornhill, , Canada

Investigational Site Number 1249004

Thornhill, , Canada

Investigational Site Number 1249007

Vancouver, , Canada

Investigational Site Number 1249002

Victoriaville, , Canada

Investigational Site Number 4849001

Aguascalientes, , Mexico

Investigational Site Number 4849006

Aguascalientes, Aguascalientes, , Mexico

Investigational Site Number 4849003

Cuernavaca, , Mexico

Investigational Site Number 4849002

Guadalajara Jalisco, , Mexico

Investigational Site Number 4849004

Monterrey, , Mexico

Investigational Site Number 4849005

Xalapa, , Mexico

Investigational Site Number 5549004

Auckland, , New Zealand

Investigational Site Number 5549003

Christchurch, , New Zealand

Investigational Site Number 5549001

Rotorua, , New Zealand

Investigational Site Number 5549002

Wellington, , New Zealand

Investigational Site Number 6439007

Kemerovo, , Russia

Investigational Site Number 6439005

Novosibirsk, , Russia

Investigational Site Number 6439001

Saint Petersburg, , Russia

Investigational Site Number 6439002

Saint Petersburg, , Russia

Investigational Site Number 6439003

Saint Petersburg, , Russia

Investigational Site Number 6439006

Yaroslavl, , Russia

Investigational Site Number 4109006

Daejeon, , South Korea

Investigational Site Number 4109005

Guri-Si, Gyeonggi-Do, , South Korea

Investigational Site Number 4109003

Gyeonggi-do, , South Korea

Investigational Site Number 4109004

Seoul, , South Korea

Investigational Site Number 4109001

Seoul, , South Korea

Investigational Site Number 1589005

Changhua, , Taiwan

Investigational Site Number 1589008

New Taipei City, , Taiwan

Investigational Site Number 1589006

Taichung, , Taiwan

Investigational Site Number 1589007

Taichung, , Taiwan

Investigational Site Number 1589001

Tainan City, , Taiwan

Investigational Site Number 1589002

Tainan City, , Taiwan

Investigational Site Number 1589004

Taipei, , Taiwan

Investigational Site Number 1589003

Taipei, , Taiwan

Countries

United States; Australia; Canada; Mexico; New Zealand; Russia; South Korea; Taiwan

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-002041-30

Identifier Type: -

Identifier Source: secondary_id

U1111-1195-6371

Identifier Type: OTHER

Identifier Source: secondary_id

EFC15294

Identifier Type: -

Identifier Source: org_study_id