Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus on Background of Sulfonylurea Alone or With Metformin

NCT03066830 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC148352016-002826-35U1111-1186-2612
• Study Type: interventional
• Target: 507
• Locations: 10 countries
• Sites: 76

Brief Summary

Primary Objective: To demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo on Hemoglobin A1c (HbA1c) reduction at Week 26 in participant with type 2 diabetes (T2D) who have inadequate glycemic control with a Sulfonylurea alone or in combination with Metformin. Secondary Objectives:

• To compare Sotagliflozin 400 mg versus placebo based on:
• Change from baseline in fasting plasma glucose (FPG).
• Change from baseline in systolic blood pressure (SBP) for participants with baseline SBP ≥130 millimeter of mercury (mm Hg).
• Change from baseline in SBP for all participants.
• Change from baseline in body weight.
• Percentage of participants with HbA1c \<6.5% and \<7.0%.
• To evaluate the safety of Sotagliflozin 400 mg versus placebo throughout the 79-week trial.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26

  Missing data are imputed using the retrieved dropouts imputation method. An analysis of covariance (ANCOVA) model was used for the analysis.

  Baseline to Week 26

Secondary Outcomes (6)

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

  Baseline to Week 26

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

  Baseline to Week 12

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

  Baseline to Week 12

• Change From Baseline in Body Weight at Week 26

  Baseline to Week 26

• Percentage of Participants With HbA1c <6.5% at Week 26

  Week 26

Other Outcomes (1)

• Percentage of Participants With Hypoglycemic Events

  Up to 79 weeks in the treatment period

Study Arms (2)

Sotagliflozin 400 mg

EXPERIMENTAL

Following a 2-week run-in phase, participants received two Sotagliflozin tablets of 200 mg, orally once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed 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 79 weeks.

Drug: Sotagliflozin (SAR439954)

Placebo

PLACEBO COMPARATOR

Following a 2-week run-in period, participants were randomized to matching placebo administered as 2 tablets, once daily, before the first meal of the day plus Metformin and Sulfonylurea as prescribed 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 79 weeks.

Drug: Placebo; Drug: Metformin; Drug: Sulfonylurea

Interventions

Sotagliflozin (SAR439954) DRUG

Pharmaceutical form: tablet Route of administration: oral

Sotagliflozin 400 mg

Placebo DRUG

Pharmaceutical form: tablet Route of administration: oral

Placebo

Metformin DRUG

Pharmaceutical form: tablet Route of administration: oral

Placebo

Sulfonylurea DRUG

Pharmaceutical form: tablet Route of administration: oral

Placebo

Eligibility Criteria

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

You may qualify if:

• Participants with T2D treated with a Sulfonylurea (≥half the maximum recommended dose as per local label or maximum tolerated dose \[documented\]) as monotherapy or in combination with Metformin (≥1500 mg per day or maximum tolerated dose \[documented\]) each at a stable dose for at least 12 weeks without a dose adjustment before screening.
• Signed written informed consent.

You may not qualify if:

• At the time of screening, age \<18 years or \< legal age of majority, whichever is greater.
• Body Mass Index (BMI) ≤20 or \>45 kilograms per meter square (kg/m\^2) at Screening.
• Hemoglobin A1c (HbA1c) \<7% or HbA1c \>10% via central lab test at screening.
• Fasting plasma glucose (FPG) \>15 mmol/L (270 mg/dL) measured by the central laboratory at screening (Visit 1), and confirmed (\>15 mmol/L \[270 mg/dL\]) by a repeat test before randomization.
• Women of childbearing potential with no effective contraceptive method.
• Treated with an antidiabetic pharmacological regimen other than a Sulfonylurea at a stable dose with or without Metformin within 12 weeks preceding the screening visit.
• Previous insulin use \>1 month (at any time, aside from treatment of gestational diabetes).
• History of prior gastric surgical procedure including gastric banding or inflammatory bowel disease within 3 years before the Screening Visit.
• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.
• History of severe hypoglycemia within 6 months prior to the Screening visit.
• Systolic blood pressure (SBP) \>180 millimeter per mercury (mmHg) or diastolic blood pressure (DBP) \>100 mmHg or history of hypertensive emergency.
• Aspartate aminotransferase and/or alanine aminotransferase: \>3 times the upper limit of the normal laboratory range (ULN).
• Total bilirubin: \>1.5 times ULN (except in case of Gilbert's syndrome).
• Use of systemic glucocorticoids (excluding topical or ophthalmic, application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.
• Pregnancy, breastfeeding.

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (76)

Investigational Site Number 8403003

Litchfield Park, Arizona, 85340, United States

Location

Investigational Site Number 8403018

Peoria, Arizona, 85381, United States

Location

Investigational Site Number 8403009

Greenbrae, California, 94904, United States

Location

Investigational Site Number 8403012

Huntington Park, California, 90255, United States

Location

Investigational Site Number 8403019

Los Angeles, California, 90057, United States

Location

Investigational Site Number 8403034

Montclair, California, 91763, United States

Location

Investigational Site Number 8403016

Spring Valley, California, 91978, United States

Location

Investigational Site Number 8403014

Tustin, California, 92780, United States

Location

Investigational Site Number 8403001

Northglenn, Colorado, 80234, United States

Location

Investigational Site Number 8403029

Bradenton, Florida, 34201, United States

Location

Investigational Site Number 8403004

New Port Richey, Florida, 34652, United States

Location

Investigational Site Number 8403020

North Miami Beach, Florida, 33162, United States

Location

Investigational Site Number 8403026

Ocoee, Florida, 34761, United States

Location

Investigational Site Number 8403032

Orlando, Florida, 32810, United States

Location

Investigational Site Number 8403008

Palm Harbor, Florida, 34684, United States

Location

Investigational Site Number 8403006

Pembroke Pines, Florida, 33026, United States

Location

Investigational Site Number 8403013

Port Charlotte, Florida, 33952, United States

Location

Investigational Site Number 8403007

Nampa, Idaho, 83686, United States

Location

Investigational Site Number 8403011

Flint, Michigan, 48532, United States

Location

Investigational Site Number 8403025

Richfield, Minnesota, 55432, United States

Location

Investigational Site Number 8403021

Henderson, Nevada, 89014, United States

Location

Investigational Site Number 8403028

Greensboro, North Carolina, 27408, United States

Location

Investigational Site Number 8403015

Shelby, North Carolina, 28150, United States

Location

Investigational Site Number 8403033

Hatboro, Pennsylvania, 19040, United States

Location

Investigational Site Number 8403030

Kingsport, Tennessee, 37660, United States

Location

Investigational Site Number 8403002

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8403022

Houston, Texas, 77081, United States

Location

Investigational Site Number 8403005

Burke, Virginia, 22015, United States

Location

Investigational Site Number 1003003

Plovdiv, 4002, Bulgaria

Location

Investigational Site Number 1003002

Rousse, 7002, Bulgaria

Location

Investigational Site Number 1003004

Sofia, 1784, Bulgaria

Location

Investigational Site Number 2333003

Pärnu, 8001, Estonia

Location

Investigational Site Number 3483001

Balatonfüred, 8230, Hungary

Location

Investigational Site Number 3483007

Budapest, 1033, Hungary

Location

Investigational Site Number 3483008

Budapest, 1036, Hungary

Location

Investigational Site Number 3483010

Budapest, 1036, Hungary

Location

Investigational Site Number 3483004

Budapest, 1106, Hungary

Location

Investigational Site Number 3483006

Budapest, 1213, Hungary

Location

Investigational Site Number 3483011

Gyula, 5700, Hungary

Location

Investigational Site Number 3483009

Hatvan, 3000, Hungary

Location

Investigational Site Number 3483005

Kecskemét, 6000, Hungary

Location

Investigational Site Number 3483003

Pécs, 7623, Hungary

Location

Investigational Site Number 3483012

Zalaegerszeg, 8900, Hungary

Location

Investigational Site Number 6163005

Gdansk, 80-382, Poland

Location

Investigational Site Number 6163006

Gdynia, 81-537, Poland

Location

Investigational Site Number 6163003

Katowice, 40-040, Poland

Location

Investigational Site Number 6163002

Poznan, 60702, Poland

Location

Investigational Site Number 6163001

Warsaw, 01-192, Poland

Location

Investigational Site Number 6163004

Wroclaw, 50-381, Poland

Location

Investigational Site Number 6423004

Bucharest, Romania

Location

Investigational Site Number 6423002

Iași, 700732, Romania

Location

Investigational Site Number 7033006

Bratislava, 831 06, Slovakia

Location

Investigational Site Number 7033001

Bratislava, 851 01, Slovakia

Location

Investigational Site Number 7033002

Bratislava, 851 01, Slovakia

Location

Investigational Site Number 7033004

Malacky, 901 01, Slovakia

Location

Investigational Site Number 7033003

Štúrovo, 943 01, Slovakia

Location

Investigational Site Number 7033007

Trenčín, 911 01, Slovakia

Location

Investigational Site Number 4103001

Goyang-Si, Gyeonggi-Do, 10380, South Korea

Location

Investigational Site Number 4103011

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

Location

Investigational Site Number 4103003

Seongnam-Si, Gyeonggi-Do, 13620, South Korea

Location

Investigational Site Number 4103007

Seoul, 06591, South Korea

Location

Investigational Site Number 4103006

Seoul, 1830, South Korea

Location

Investigational Site Number 4103010

Seoul, 3722, South Korea

Location

Investigational Site Number 4103005

Seoul, 7345, South Korea

Location

Investigational Site Number 4103009

Wonju-Si, Gangwon-Do, 26426, South Korea

Location

Investigational Site Number 8043001

Kyiv, 2002, Ukraine

Location

Investigational Site Number 8043003

Kyiv, 3037, Ukraine

Location

Investigational Site Number 8043002

Kyiv, 3049, Ukraine

Location

Investigational Site Number 8263012

Birmingham, B15 2SQ, United Kingdom

Location

Investigational Site Number 8263009

Cardiff, CF15 9SS, United Kingdom

Location

Investigational Site Number 8263007

Glasgow, G20 0SP, United Kingdom

Location

Investigational Site Number 8263008

Hexham, NE46 1QJ, United Kingdom

Location

Investigational Site Number 8263003

Inverness, IV2 3JH, United Kingdom

Location

Investigational Site Number 8263014

Liverpool, L22 0LG, United Kingdom

Location

Investigational Site Number 8263011

Manchester, M15 6SE, United Kingdom

Location

Investigational Site Number 8263010

Reading, RG2 0TG, 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; Metformin; Sulfonylurea Compounds

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Urea; Amides; Sulfones; Sulfur Compounds

Results Point of Contact

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

medical-information@lexpharma.com

510-338-6064

Study Officials

• Suman Wason

  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: February 24, 2017
• First Posted: February 28, 2017
• Study Start: February 24, 2017
• Primary Completion: April 17, 2019
• Study Completion: April 30, 2019
• Last Updated: May 11, 2021
• Results First Posted: May 11, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will share

Locations

BU (3); KR (8); US (28); PL (6); ES (1); SL (6); RO (2); UA (3); HU (11); GB (8)