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

NCT ID: NCT03761134

Last Updated: 2022-04-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 377 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-30
• Study Completion Date: 2020-04-29

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.

Detailed Description

Total study duration is up to 30 weeks, including a screening period consisting of a screening phase of up to 2 weeks and a 2-week single-blind placebo run-in phase, a 24-week double-blind treatment period, and a 2-week post-treatment follow-up visit period to collect safety information.

Conditions

Type 2 Diabetes Mellitus

Study Design

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

Study Groups

Sotagliflozin dose 1

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

Group Type: EXPERIMENTAL

sotagliflozin (SAR439954)

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

metformin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

sulfonylurea

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Sotagliflozin dose 2

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

Group Type: EXPERIMENTAL

sotagliflozin (SAR439954)

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

placebo

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

metformin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

sulfonylurea

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Placebo

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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

metformin

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

sulfonylurea

Intervention Type: DRUG

Pharmaceutical form: tablet

Route of administration: oral

Interventions

sotagliflozin (SAR439954)

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

placebo

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

metformin

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

sulfonylurea

Pharmaceutical form: tablet

Route of administration: oral

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• Total bilirubin >1.5 times the ULN (except in case of Gilbert's syndrome).
• Use of systemic glucocorticoids (excluding topical or ophthalmic application, nasal spray, or inhaled forms) for more than 10 consecutive days within 90 days prior to the screening visit.
• Patient who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives prior to the screening visit, whichever is longer.
• Use of a selective SGLT2 inhibitor (eg, canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the screening visit.
• Pregnant (confirmed by serum pregnancy test at the screening visit) or breastfeeding women.
• Patients with severe renal disease as defined by an eGFR of <30 mL/min/1.73m² at the screening visit, based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation.
• Patients with contraindication to metformin as per local labelling.
• Patients with contraindication to sulfonylurea as per local labelling if the patient is taking metformin with sulfonylurea.
• Patient unwilling or unable 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.
• Patients unable to consume at least 50% of the standard meal during the MMTT at baseline (Day 1, Visit 3) before randomization.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 1560039

Baotou, , China

Investigational Site Number 1560040

Baotou, , China

Investigational Site Number 1560001

Beijing, , China

Investigational Site Number 1560038

Beijing, , China

Investigational Site Number 1560035

Cangzhou, , China

Investigational Site Number 1560020

Changchun, , China

Investigational Site Number 1560012

Changchun, , China

Investigational Site Number 1560011

Changsha, , China

Investigational Site Number 1560021

Changzhou, , China

Investigational Site Number 1560024

Chongqing, , China

Investigational Site Number 1560028

Dalian, , China

Investigational Site Number 1560010

Dalian, , China

Investigational Site Number 1560036

Dalian, , China

Investigational Site Number 1560030

Fuzhou, , China

Investigational Site Number 1560032

Guangzhou, , China

Investigational Site Number 1560027

Guangzhou, , China

Investigational Site Number 1560041

Hangzhou, , China

Investigational Site Number 1560046

Harbin, , China

Investigational Site Number 1560009

Hefei, , China

Investigational Site Number 1560025

Hohhot, , China

Investigational Site Number 1560026

Huai'an, , China

Investigational Site Number 1560006

Jinan, , China

Investigational Site Number 1560033

Kunming, , China

Investigational Site Number 1560034

Luoyang, , China

Investigational Site Number 1560014

Nanjing, , China

Investigational Site Number 1560018

Pingxiang, , China

Investigational Site Number 1560003

Shanghai, , China

Investigational Site Number 1560004

Shanghai, , China

Investigational Site Number 1560013

Shanghai, , China

Investigational Site Number 1560005

Shenyang, , China

Investigational Site Number 1560019

Shijiazhuang, , China

Investigational Site Number 1560017

Suzhou, , China

Investigational Site Number 1560022

Wuhan, , China

Investigational Site Number 1560023

Wuxi, , China

Investigational Site Number 1560015

Xiangtan, , China

Investigational Site Number 1560043

Yuncheng, , China

Investigational Site Number 1560042

Zhengzhou, , China

Investigational Site Number 1560007

Zhenjiang, , China

Investigational Site Number 1560037

Zhongshan, , China

Investigational Site Number 1560016

Zhuzhou, , China

Countries

China

Other Identifiers

U1111-1195-6143

Identifier Type: OTHER

Identifier Source: secondary_id

EFC15193

Identifier Type: -

Identifier Source: org_study_id