Efficacy and Safety of Sotagliflozin Versus Placebo in Chinese Patients With Type 2 Diabetes Mellitus Not Adequately Controlled by Metformin With or Without Sulfonylurea

NCT03761134 | Terminated Phase 3

• 2 other identifiers: EFC15193U1111-1195-6143
• Study Type: interventional
• Target: 377
• Locations: 1 country
• Sites: 40

Brief Summary

Primary Objective: To demonstrate the superiority of sotagliflozin dose 1 versus placebo on hemoglobin A1c (HbA1c) reduction in Chinese patients with type 2 diabetes (T2D) who have inadequate glycemic control on metformin alone or metformin in combination with sulfonylurea. Secondary Objectives: To compare sotagliflozin dose 1 versus placebo for change in 2-hour postprandial glucose (PPG) following a mixed meal tolerance test (MMTT), change in fasting plasma glucose (FPG), and change in body weight.

• To compare sotagliflozin dose 2 versus placebo for change in HbA1c, change in 2-hour PPG following a MMTT, change in FPG, and change in body weight.
• To compare sotagliflozin dose 2 and sotagliflozin dose 1 versus placebo for change in systolic blood pressure (SBP) for all patients, and change in SBP for patients with baseline SBP ≥130 mmHg.
• To evaluate the safety of sotagliflozin dose 2 and sotagliflozin dose 1 versus placebo.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change in hemoglobin A1c (HbA1c)

  Absolute change from baseline to week 24 in HbA1c (for sotagliflozin dose 1)

  Baseline to Week 24

Secondary Outcomes (7)

• Change in 2-hour postprandial glucose (PPG) following a mixed meal tolerance test (MMTT)

  Baseline to Week 24

• Change in fasting plasma glucose (FPG)

  Baseline to Week 24

• Change in body weight

  Baseline to Week 24

• Change in HbA1c

  Baseline to Week 24

• Change in systolic blood pressure (SBP) for all patients

  Baseline to Week 12

Study Arms (3)

Sotagliflozin dose 1

EXPERIMENTAL

Sotagliflozin dose 1, given as two (2) dose 2 tablets, once daily, before the first meal of the day

Drug: sotagliflozin (SAR439954); Drug: metformin; Drug: sulfonylurea

Sotagliflozin dose 2

EXPERIMENTAL

Sotagliflozin dose 2, given as 1 sotagliflozin dose 2 tablet and 1 sotagliflozin-matching placebo tablet (identical to sotagliflozin dose 2 in appearance), once daily, before the first meal of the day

Drug: sotagliflozin (SAR439954); Drug: placebo; Drug: metformin; Drug: sulfonylurea

Placebo

PLACEBO COMPARATOR

Two sotagliflozin-matching placebo tablets (identical to sotagliflozin dose 2 in appearance), once daily, before the first meal of the day

Drug: placebo; Drug: metformin; Drug: sulfonylurea

Interventions

sotagliflozin (SAR439954) DRUG

Pharmaceutical form: tablet Route of administration: oral

Sotagliflozin dose 1; Sotagliflozin dose 2

placebo DRUG

Pharmaceutical form: tablet Route of administration: oral

Placebo; Sotagliflozin dose 2

metformin DRUG

Pharmaceutical form: tablet Route of administration: oral

Placebo; Sotagliflozin dose 1; Sotagliflozin dose 2

sulfonylurea DRUG

Pharmaceutical form: tablet Route of administration: oral

Placebo; Sotagliflozin dose 1; Sotagliflozin dose 2

Eligibility Criteria

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

You may qualify if:

• Chinese patients with T2D diagnosed for at least 1 year, who are treated with diet/exercise and:
• Metformin alone at a stable dose ( ≥1500 mg/day or maximum tolerated dose \[documented\]) for at least 8 weeks before the screening visit OR
• Metformin in combination with sulfonylurea (≥ half maximum-labelled dose or maximum tolerated dose \[documented\]) each at a stable dose for at least 8 weeks before the screening visit.
• Signed written informed consent.

You may not qualify if:

• Age \<18 years at the screening visit.
• Type 1 diabetes.
• Hemoglobin A1c \<7% or \>10.5% measured by the central laboratory at the screening visit.
• Fasting plasma glucose \>15 mmol/L (\>270 mg/dL) measured by the central laboratory at the screening visit and confirmed by a repeat test (\>15 mmol/L \[\>270 mg/dL\]) before randomization.
• Body mass index (BMI) ≤20 or \>45 kg/m2 at the screening visit.
• 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.
• Previous use of any antidiabetic drug other than metformin and sulphonylurea within the 12 weeks prior to the screening visit.
• Previous use of any types of insulin for \>1 month within 12 months before screening.
• History of gastric surgery including history of gastric banding or inflammatory bowel disease within 3 years prior to the screening visit.
• History of diabetic ketoacidosis (DKA) or non-ketotic hyperosmolar coma within 12 weeks prior to the screening visit.
• History of serious hypoglycemia resulting in unconsciousness, seizure or hospitalization within 6 months prior to the screening visit.
• Mean of 3 separate blood pressure measurements \>180 mmHg (SBP) or \>100 mmHg (diastolic blood pressure DBP (DBP)).
• History of hypertensive emergency within 12 weeks prior to the screening visit.
• Patients with severe anemia, severe cardiovascular (CV) (including congestive heart failure New York Heart Association (NYHA) IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease or patients with short life expectancy that, according to Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3 times the upper limit of the normal (ULN) laboratory range.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (40)

Investigational Site Number 1560039

Baotou, 014010, China

Location

Investigational Site Number 1560040

Baotou, 014010, China

Location

Investigational Site Number 1560001

Beijing, 100029, China

Location

Investigational Site Number 1560038

Beijing, 100191, China

Location

Investigational Site Number 1560035

Cangzhou, 061000, China

Location

Investigational Site Number 1560020

Changchun, 130033, China

Location

Investigational Site Number 1560012

Changchun, 130041, China

Location

Investigational Site Number 1560011

Changsha, 410011, China

Location

Investigational Site Number 1560021

Changzhou, 213003, China

Location

Investigational Site Number 1560024

Chongqing, 400010, China

Location

Investigational Site Number 1560028

Dalian, 116011, China

Location

Investigational Site Number 1560010

Dalian, 116033, China

Location

Investigational Site Number 1560036

Dalian, China

Location

Investigational Site Number 1560030

Fuzhou, 354200, China

Location

Investigational Site Number 1560032

Guangzhou, 510080, China

Location

Investigational Site Number 1560027

Guangzhou, 510180, China

Location

Investigational Site Number 1560041

Hangzhou, China

Location

Investigational Site Number 1560046

Harbin, 150001, China

Location

Investigational Site Number 1560009

Hefei, 230001, China

Location

Investigational Site Number 1560025

Hohhot, 010017, China

Location

Investigational Site Number 1560026

Huai'an, 223300, China

Location

Investigational Site Number 1560006

Jinan, 250013, China

Location

Investigational Site Number 1560033

Kunming, China

Location

Investigational Site Number 1560034

Luoyang, China

Location

Investigational Site Number 1560014

Nanjing, 210011, China

Location

Investigational Site Number 1560018

Pingxiang, 337055, China

Location

Investigational Site Number 1560003

Shanghai, 200072, China

Location

Investigational Site Number 1560004

Shanghai, 201700, China

Location

Investigational Site Number 1560013

Shanghai, China

Location

Investigational Site Number 1560005

Shenyang, 110004, China

Location

Investigational Site Number 1560019

Shijiazhuang, China

Location

Investigational Site Number 1560017

Suzhou, 215004, China

Location

Investigational Site Number 1560022

Wuhan, 430014, China

Location

Investigational Site Number 1560023

Wuxi, 214023, China

Location

Investigational Site Number 1560015

Xiangtan, China

Location

Investigational Site Number 1560043

Yuncheng, 044000, China

Location

Investigational Site Number 1560042

Zhengzhou, 450003, China

Location

Investigational Site Number 1560007

Zhenjiang, 212001, China

Location

Investigational Site Number 1560037

Zhongshan, China

Location

Investigational Site Number 1560016

Zhuzhou, 412007, China

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

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

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: November 29, 2018
• First Posted: December 3, 2018
• Study Start: November 30, 2018
• Primary Completion: April 29, 2020
• Study Completion: April 29, 2020
• Last Updated: April 25, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (40)