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

NCT03285594 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC148682016-001804-43U1111-1190-7567
• Study Type: interventional
• Target: 571
• Locations: 8 countries
• Sites: 106

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18

  An analysis of covariance (ANCOVA) model was used for the analysis.

  Baseline and Week 18

Secondary Outcomes (7)

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18

  Baseline and Week 18

• Change From Baseline in Body Weight at Week 18

  Baseline and Week 18

• Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12

  Baseline and Week 12

• Change From Baseline in SBP at Week 12 for All Participants

  Baseline to Week 12

• Change From Baseline in HbA1c at Week 52

  Baseline and Week 52

Other Outcomes (1)

• Percentage of Participants With Hypoglycemic Events

  Up to 55.7 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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.

Drug: Insulin glargine (HOE901); Drug: Placebo; Drug: Oral Antidiabetes Drugs (OADs)

Sotagliflozin 200 mg

EXPERIMENTAL

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.

Drug: Sotagliflozin; Drug: Insulin glargine (HOE901); Drug: Placebo; Drug: Oral Antidiabetes Drugs (OADs)

Sotagliflozin 400 mg

EXPERIMENTAL

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.

Drug: Sotagliflozin; Drug: Insulin glargine (HOE901); Drug: Oral Antidiabetes Drugs (OADs)

Interventions

Sotagliflozin DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Also known as: SAR439954

Sotagliflozin 200 mg; Sotagliflozin 400 mg

Insulin glargine (HOE901) DRUG

Pharmaceutical form: Solution Route of administration: Subcutaneous

Also known as: Lantus

Placebo; Sotagliflozin 200 mg; Sotagliflozin 400 mg

Placebo DRUG

Pharmaceutical form: Tablet Route of administration: Oral

Placebo; Sotagliflozin 200 mg

Oral Antidiabetes Drugs (OADs) DRUG

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

Placebo; Sotagliflozin 200 mg; Sotagliflozin 400 mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (106)

Investigational Site Number 8406028

Mesa, Arizona, 85213-5226, United States

Location

Investigational Site Number 8406013

Phoenix, Arizona, 85018, United States

Location

Investigational Site Number 8406020

Phoenix, Arizona, 85020, United States

Location

Investigational Site Number 8406006

Huntington Park, California, 90255, United States

Location

Investigational Site Number 8406053

Lincoln, California, 95648, United States

Location

Investigational Site Number 8406040

Los Angeles, California, 90057, United States

Location

Investigational Site Number 8406043

Coral Gables, Florida, 33134, United States

Location

Investigational Site Number 8406008

DeLand, Florida, 32720, United States

Location

Investigational Site Number 8406030

Maitland, Florida, 32751, United States

Location

Investigational Site Number 8406003

New Port Richey, Florida, 34652, United States

Location

Investigational Site Number 8406029

North Miami Beach, Florida, 33162, United States

Location

Investigational Site Number 8406052

Ocoee, Florida, 34761, United States

Location

Investigational Site Number 8406001

Port Charlotte, Florida, 33952, United States

Location

Investigational Site Number 8406022

St. Petersburg, Florida, 33700, United States

Location

Investigational Site Number 8406025

Tampa, Florida, 33634, United States

Location

Investigational Site Number 8406002

West Palm Beach, Florida, 33401-3430, United States

Location

Investigational Site Number 8406054

Chicago, Illinois, 60602, United States

Location

Investigational Site Number 8406027

Chicago, Illinois, 60604, United States

Location

Investigational Site Number 8406042

Evansville, Indiana, 47714, United States

Location

Investigational Site Number 8406044

New Orleans, Louisiana, 70119-6302, United States

Location

Investigational Site Number 8406051

New Orleans, Louisiana, 70124, United States

Location

Investigational Site Number 8406024

Rockville, Maryland, 20852, United States

Location

Investigational Site Number 8406016

Detroit, Michigan, 48202, United States

Location

Investigational Site Number 8406011

St Louis, Missouri, 63110, United States

Location

Investigational Site Number 8406010

Papillion, Nebraska, 68046-3136, United States

Location

Investigational Site Number 8406018

New York, New York, 10016-6023, United States

Location

Investigational Site Number 8406034

Asheville, North Carolina, 28803, United States

Location

Investigational Site Number 8406046

Chapel Hill, North Carolina, 27517, United States

Location

Investigational Site Number 8406026

Charlotte, North Carolina, 28209, United States

Location

Investigational Site Number 8406038

Greenville, North Carolina, 27834, United States

Location

Investigational Site Number 8406036

Hickory, North Carolina, 28601, United States

Location

Investigational Site Number 8406015

Wilmington, North Carolina, 28401-6638, United States

Location

Investigational Site Number 8406019

Winston-Salem, North Carolina, 27103, United States

Location

Investigational Site Number 8406031

Beachwood, Ohio, 44122, United States

Location

Investigational Site Number 8406023

Columbus, Ohio, 43201, United States

Location

Investigational Site Number 8406005

Dublin, Ohio, 43016, United States

Location

Investigational Site Number 8406004

Mentor, Ohio, 44060, United States

Location

Investigational Site Number 8406033

Oklahoma City, Oklahoma, 73111, United States

Location

Investigational Site Number 8406032

Moncks Corner, South Carolina, 29461-5017, United States

Location

Investigational Site Number 8406009

Chattanooga, Tennessee, 37421, United States

Location

Investigational Site Number 8406045

Seymour, Tennessee, 37865-5270, United States

Location

Investigational Site Number 8406047

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8406017

Dallas, Texas, 75231, United States

Location

Investigational Site Number 8406048

Houston, Texas, 77079, United States

Location

Investigational Site Number 8406037

Houston, Texas, 77099, United States

Location

Investigational Site Number 8406039

McAllen, Texas, 78504, United States

Location

Investigational Site Number 8406050

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 8406021

Shavano Park, Texas, 78231, United States

Location

Investigational Site Number 8406035

Salt Lake City, Utah, 84102-1553, United States

Location

Investigational Site Number 8406014

West Jordan, Utah, 84088-8865, United States

Location

Investigational Site Number 1006009

Gabrovo, 5300, Bulgaria

Location

Investigational Site Number 1006003

Plovdiv, 4002, Bulgaria

Location

Investigational Site Number 1006004

Rousse, 7002, Bulgaria

Location

Investigational Site Number 1006001

Rousse, 7003, Bulgaria

Location

Investigational Site Number 1006006

Smolyan, 4700, Bulgaria

Location

Investigational Site Number 1006002

Sofia, 1606, Bulgaria

Location

Investigational Site Number 1006010

Sofia, 1750, Bulgaria

Location

Investigational Site Number 1006005

Stara Zagora, 6000, Bulgaria

Location

Investigational Site Number 1006007

Varna, 9000, Bulgaria

Location

Investigational Site Number 1246003

Brampton, L6S 0C9, Canada

Location

Investigational Site Number 1246005

Burlington, L7R 1E2, Canada

Location

Investigational Site Number 1246004

Etobicoke, M9R 4E1, Canada

Location

Investigational Site Number 1246002

Toronto, M4G 3E8, Canada

Location

Investigational Site Number 1246001

Vancouver, V5Y 3W2, Canada

Location

Investigational Site Number 2036003

Holešov, 769 01, Czechia

Location

Investigational Site Number 2036002

Krnov, 794 01, Czechia

Location

Investigational Site Number 2036001

Olomouc, 779 00, Czechia

Location

Investigational Site Number 2036005

Ostrava, 702 00, Czechia

Location

Investigational Site Number 2036007

Prague, 140 46, Czechia

Location

Investigational Site Number 2036008

Prague, 149 00, Czechia

Location

Investigational Site Number 2036006

Praha 10 - Uhrineves, 104 00, Czechia

Location

Investigational Site Number 2506008

Besançon, 25030, France

Location

Investigational Site Number 2506003

Corbeil-Essonnes, 91106, France

Location

Investigational Site Number 2506005

Dijon, 21079, France

Location

Investigational Site Number 2506012

Mulhouse, 68100, France

Location

Investigational Site Number 2506004

Nantes, 44093, France

Location

Investigational Site Number 2506007

Narbonne, 11100, France

Location

Investigational Site Number 2506006

Paris, 75018, France

Location

Investigational Site Number 2506010

Pierre-Bénite, 69495, France

Location

Investigational Site Number 2506009

Poitiers, 86021, France

Location

Investigational Site Number 2506011

Saint-Mandé, 94160, France

Location

Investigational Site Number 2506002

Vénissieux, 69200, France

Location

Investigational Site Number 3486007

Budapest, 1106, Hungary

Location

Investigational Site Number 3486002

Budapest, 1134, Hungary

Location

Investigational Site Number 3486006

Hatvan, 3000, Hungary

Location

Investigational Site Number 3486009

Kecskemét, 6000, Hungary

Location

Investigational Site Number 3486003

Komárom, 2900, Hungary

Location

Investigational Site Number 3486005

Nyíregyháza, 4400, Hungary

Location

Investigational Site Number 3486001

Pécs, 7623, Hungary

Location

Investigational Site Number 3486008

Zalaegerszeg, 8900, Hungary

Location

Investigational Site Number 7036004

Bardejov, 085 01, Slovakia

Location

Investigational Site Number 7036008

Bratislava, 831 06, Slovakia

Location

Investigational Site Number 7036001

Bratislava, 85101, Slovakia

Location

Investigational Site Number 7036010

Košice, 040 01, Slovakia

Location

Investigational Site Number 7036003

Košice, 4014, Slovakia

Location

Investigational Site Number 7036007

Levice, 934 01, Slovakia

Location

Investigational Site Number 7036009

Levice, 934 05, Slovakia

Location

Investigational Site Number 7036011

Lučenec, 98401, Slovakia

Location

Investigational Site Number 7036006

Nitra, 949 11, Slovakia

Location

Investigational Site Number 7036005

Sabinov, 08301, Slovakia

Location

Investigational Site Number 8266002

Darlington, DL3 6HX, United Kingdom

Location

Investigational Site Number 8266006

Doncaster, DN9 2HY, United Kingdom

Location

Investigational Site Number 8266008

Dundee, DD1 9SY, United Kingdom

Location

Investigational Site Number 8266001

Leicester, LE5 4PW, United Kingdom

Location

Investigational Site Number 8266004

London, EC1M 6BQ, United Kingdom

Location

Investigational Site Number 8266003

Salford, M6 8HD, United Kingdom

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; Insulin Glargine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

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: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 18, 2017
• Study Start: September 15, 2017
• Primary Completion: September 17, 2019
• Study Completion: September 27, 2019
• Last Updated: May 11, 2021
• Results First Posted: May 11, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

HU (8); GB (6); FR (11); CA (5); US (50); SL (10); BU (9); CZ (7)