Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking Insulin Alone or With Other Oral Antidiabetic Agents

NCT ID: NCT03285594

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 571 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-09-15
• Study Completion Date: 2019-09-27

Brief Summary

Primary Objective:

To demonstrate the superiority of sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1C (HbA1c) reduction in participants with type 2 diabetes mellitus (T2D) who have inadequate glycemic control on basal insulin alone or with oral antidiabetes drugs (OADs).

Secondary Objectives:

• To assess the effects of sotagliflozin 400 mg versus placebo on fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), and HbA1c.
• To assess the effects of sotagliflozin 200 mg versus placebo on HbA1c, body weight, FPG, and SBP.
• To evaluate the safety of sotagliflozin 400 and 200 mg versus placebo.

Detailed Description

Up to 60 weeks (Screening phase of up to 2 weeks, a 4-week Lantus titration/single-blind placebo Run-in phase), a 52-week double blind Treatment Period, and a 2-week post-treatment Follow-up Period.

Conditions

Type 2 Diabetes Mellitus

Study Design

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

Study Groups

Placebo

Following a 4-week run-in period, participants were randomized to matching placebo to sotagliflozin 200 milligrams (mg) administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.

Group Type: PLACEBO_COMPARATOR

Insulin glargine (HOE901)

Intervention Type: DRUG

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Placebo

Intervention Type: DRUG

Pharmaceutical form: Tablet

Route of administration: Oral

Oral Antidiabetes Drugs (OADs)

Intervention Type: DRUG

OADs (including metformin) as prescribed by the investigator as per local labeling.

Sotagliflozin 200 mg

Following a 4-week run-in period, participants were randomized to sotagliflozin 200 mg administered as 1 tablet and matching placebo as 1 tablet, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.

Group Type: EXPERIMENTAL

Sotagliflozin

Intervention Type: DRUG

Pharmaceutical form: Tablet

Route of administration: Oral

Insulin glargine (HOE901)

Intervention Type: DRUG

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Placebo

Intervention Type: DRUG

Pharmaceutical form: Tablet

Route of administration: Oral

Oral Antidiabetes Drugs (OADs)

Intervention Type: DRUG

OADs (including metformin) as prescribed by the investigator as per local labeling.

Sotagliflozin 400 mg

Following a 4-week run-in period, participants were randomized to sotagliflozin 400 mg administered as 2 tablets, once daily, before the first meal of the day in the double-blind treatment period for up to 52 weeks. Background therapy with insulin glargine (with or without OADs) continued throughout the study.

Group Type: EXPERIMENTAL

Sotagliflozin

Intervention Type: DRUG

Pharmaceutical form: Tablet

Route of administration: Oral

Insulin glargine (HOE901)

Intervention Type: DRUG

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Oral Antidiabetes Drugs (OADs)

Intervention Type: DRUG

OADs (including metformin) as prescribed by the investigator as per local labeling.

Interventions

Sotagliflozin

Pharmaceutical form: Tablet

Route of administration: Oral

Intervention Type: DRUG

Insulin glargine (HOE901)

Pharmaceutical form: Solution

Route of administration: Subcutaneous

Intervention Type: DRUG

Placebo

Pharmaceutical form: Tablet

Route of administration: Oral

Intervention Type: DRUG

Oral Antidiabetes Drugs (OADs)

OADs (including metformin) as prescribed by the investigator as per local labeling.

Intervention Type: DRUG

Other Intervention Names

SAR439954; Lantus

Eligibility Criteria

Inclusion Criteria

• Participants with Type 2 Diabetes Mellitus (T2DM) using any types of basal insulin alone or in combination with up to 2 OADs.
• Participants have given written informed consent to participate in the study in accordance with local regulations.

Exclusion Criteria

• At the time of Screening age <18 years or <legal age of majority, whichever is greater.
• Type 1 diabetes mellitus.
• Oral antidiabetic drugs dose not stable for 8 weeks before Screening.
• Use of basal insulin therapy (e.g., insulin glargine, Neutral Protamine Hagedorn (NPH), detemir, or degludec) for less than 6 months before Screening.
• Dose of basal insulin (e.g., insulin glargine, NPH, detemir, or degludec) not stable for 8 weeks before Screening (i.e., total daily insulin dose increased or decreased by more than 20%).
• Known unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema that is likely to require laser, surgical treatment during study period.
• Use of injectable diabetes drugs other than basal insulin (e.g., insulin glargine, NPH, detemir, or degludec), i.e., prandial or rapid-acting insulins, short-acting insulins, glucagon-like peptide 1 (GLP-1) receptor agonists, or inhaled prandial insulin (Afrezza) within 8 weeks of Screening.
• Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the trial.
• Use of systemic glucocorticoids (excluding topical, intra articular, or ophthalmic application, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
• Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease that, according to the Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.
• Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization.
• Known presence of factors that interfere with the Central Lab HbA1c measurement (e.g., genetic hemoglobin (Hb) variants) compromising the reliability of HbA1c assessment or medical conditions that affect interpretation of HbA1c results (e.g., blood transfusion or severe blood loss in the last 3 months prior to randomization, any condition that shortens erythrocyte survival).
• Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from prior to Screening, whichever is longer.
• Participants unwilling to perform self-monitoring of blood glucose (SMBG), complete the patient diary, or comply with study visits and other study procedures as required per protocol.
• HbA1c <7.5% or HbA1c >10.5% measured by the central laboratory at Screening.
• HbA1c <7% measured by the central laboratory at Visit 5 (Week -1).
• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
• Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.
• Women of childbearing potential not willing to use highly effective method(s) of birth control during the study treatment period and the follow-up period, or who are unwilling or unable to be tested for pregnancy during the study.
• Mean of 3 separate blood pressure measurements >180 mmHg (systolic blood pressure [SBP]) or >100 mmHg (diastolic blood pressure [DBP]).
• History of gastric surgery including history of gastric banding or inflammatory bowel disease within 3 years prior to the Screening Visit.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >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).

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 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 8406028

Mesa, Arizona, United States

Investigational Site Number 8406013

Phoenix, Arizona, United States

Investigational Site Number 8406020

Phoenix, Arizona, United States

Investigational Site Number 8406006

Huntington Park, California, United States

Investigational Site Number 8406053

Lincoln, California, United States

Investigational Site Number 8406040

Los Angeles, California, United States

Investigational Site Number 8406043

Coral Gables, Florida, United States

Investigational Site Number 8406008

DeLand, Florida, United States

Investigational Site Number 8406030

Maitland, Florida, United States

Investigational Site Number 8406003

New Port Richey, Florida, United States

Investigational Site Number 8406029

North Miami Beach, Florida, United States

Investigational Site Number 8406052

Ocoee, Florida, United States

Investigational Site Number 8406001

Port Charlotte, Florida, United States

Investigational Site Number 8406022

St. Petersburg, Florida, United States

Investigational Site Number 8406025

Tampa, Florida, United States

Investigational Site Number 8406002

West Palm Beach, Florida, United States

Investigational Site Number 8406054

Chicago, Illinois, United States

Investigational Site Number 8406027

Chicago, Illinois, United States

Investigational Site Number 8406042

Evansville, Indiana, United States

Investigational Site Number 8406044

New Orleans, Louisiana, United States

Investigational Site Number 8406051

New Orleans, Louisiana, United States

Investigational Site Number 8406024

Rockville, Maryland, United States

Investigational Site Number 8406016

Detroit, Michigan, United States

Investigational Site Number 8406011

St Louis, Missouri, United States

Investigational Site Number 8406010

Papillion, Nebraska, United States

Investigational Site Number 8406018

New York, New York, United States

Investigational Site Number 8406034

Asheville, North Carolina, United States

Investigational Site Number 8406046

Chapel Hill, North Carolina, United States

Investigational Site Number 8406026

Charlotte, North Carolina, United States

Investigational Site Number 8406038

Greenville, North Carolina, United States

Investigational Site Number 8406036

Hickory, North Carolina, United States

Investigational Site Number 8406015

Wilmington, North Carolina, United States

Investigational Site Number 8406019

Winston-Salem, North Carolina, United States

Investigational Site Number 8406031

Beachwood, Ohio, United States

Investigational Site Number 8406023

Columbus, Ohio, United States

Investigational Site Number 8406005

Dublin, Ohio, United States

Investigational Site Number 8406004

Mentor, Ohio, United States

Investigational Site Number 8406033

Oklahoma City, Oklahoma, United States

Investigational Site Number 8406032

Moncks Corner, South Carolina, United States

Investigational Site Number 8406009

Chattanooga, Tennessee, United States

Investigational Site Number 8406045

Seymour, Tennessee, United States

Investigational Site Number 8406047

Dallas, Texas, United States

Investigational Site Number 8406017

Dallas, Texas, United States

Investigational Site Number 8406048

Houston, Texas, United States

Investigational Site Number 8406037

Houston, Texas, United States

Investigational Site Number 8406039

McAllen, Texas, United States

Investigational Site Number 8406050

San Antonio, Texas, United States

Investigational Site Number 8406021

Shavano Park, Texas, United States

Investigational Site Number 8406035

Salt Lake City, Utah, United States

Investigational Site Number 8406014

West Jordan, Utah, United States

Investigational Site Number 1006009

Gabrovo, , Bulgaria

Investigational Site Number 1006003

Plovdiv, , Bulgaria

Investigational Site Number 1006004

Rousse, , Bulgaria

Investigational Site Number 1006001

Rousse, , Bulgaria

Investigational Site Number 1006006

Smolyan, , Bulgaria

Investigational Site Number 1006002

Sofia, , Bulgaria

Investigational Site Number 1006010

Sofia, , Bulgaria

Investigational Site Number 1006005

Stara Zagora, , Bulgaria

Investigational Site Number 1006007

Varna, , Bulgaria

Investigational Site Number 1246003

Brampton, , Canada

Investigational Site Number 1246005

Burlington, , Canada

Investigational Site Number 1246004

Etobicoke, , Canada

Investigational Site Number 1246002

Toronto, , Canada

Investigational Site Number 1246001

Vancouver, , Canada

Investigational Site Number 2036003

Holešov, , Czechia

Investigational Site Number 2036002

Krnov, , Czechia

Investigational Site Number 2036001

Olomouc, , Czechia

Investigational Site Number 2036005

Ostrava, , Czechia

Investigational Site Number 2036007

Prague, , Czechia

Investigational Site Number 2036008

Prague, , Czechia

Investigational Site Number 2036006

Praha 10 - Uhrineves, , Czechia

Investigational Site Number 2506008

Besançon, , France

Investigational Site Number 2506003

Corbeil-Essonnes, , France

Investigational Site Number 2506005

Dijon, , France

Investigational Site Number 2506012

Mulhouse, , France

Investigational Site Number 2506004

Nantes, , France

Investigational Site Number 2506007

Narbonne, , France

Investigational Site Number 2506006

Paris, , France

Investigational Site Number 2506010

Pierre-Bénite, , France

Investigational Site Number 2506009

Poitiers, , France

Investigational Site Number 2506011

Saint-Mandé, , France

Investigational Site Number 2506002

Vénissieux, , France

Investigational Site Number 3486007

Budapest, , Hungary

Investigational Site Number 3486002

Budapest, , Hungary

Investigational Site Number 3486006

Hatvan, , Hungary

Investigational Site Number 3486009

Kecskemét, , Hungary

Investigational Site Number 3486003

Komárom, , Hungary

Investigational Site Number 3486005

Nyíregyháza, , Hungary

Investigational Site Number 3486001

Pécs, , Hungary

Investigational Site Number 3486008

Zalaegerszeg, , Hungary

Investigational Site Number 7036004

Bardejov, , Slovakia

Investigational Site Number 7036008

Bratislava, , Slovakia

Investigational Site Number 7036001

Bratislava, , Slovakia

Investigational Site Number 7036010

Košice, , Slovakia

Investigational Site Number 7036003

Košice, , Slovakia

Investigational Site Number 7036007

Levice, , Slovakia

Investigational Site Number 7036009

Levice, , Slovakia

Investigational Site Number 7036011

Lučenec, , Slovakia

Investigational Site Number 7036006

Nitra, , Slovakia

Investigational Site Number 7036005

Sabinov, , Slovakia

Investigational Site Number 8266002

Darlington, , United Kingdom

Investigational Site Number 8266006

Doncaster, , United Kingdom

Investigational Site Number 8266008

Dundee, , United Kingdom

Investigational Site Number 8266001

Leicester, , United Kingdom

Investigational Site Number 8266004

London, , United Kingdom

Investigational Site Number 8266003

Salford, , United Kingdom

Countries

United States; Bulgaria; Canada; Czechia; France; Hungary; Slovakia; United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-001804-43

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1190-7567

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14868

Identifier Type: -

Identifier Source: org_study_id