Clinical trial NCT03761134: Efficacy and Safety of Sotagliflozin Versus Placebo in Chinese Patients With Type 2 Diabetes Mellitus Not Adequately Controlled by Metformin With or Without Sulfonylurea
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin in Chinese Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone or Metformin in Combination With Sulfonylurea
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-12-03
Enrollment: 377
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in hemoglobin A1c (HbA1c)
timeFrame: Baseline to Week 24
Secondary outcomes:
measure: Change in 2-hour postprandial glucose (PPG) following a mixed meal tolerance test (MMTT)
timeFrame: Baseline to Week 24
measure: Change in fasting plasma glucose (FPG)
timeFrame: Baseline to Week 24
measure: Change in body weight
timeFrame: Baseline to Week 24
measure: Change in HbA1c
timeFrame: Baseline to Week 24
measure: Change in systolic blood pressure (SBP) for all patients
timeFrame: Baseline to Week 12
measure: Change in SBP for patients with baseline SBP ≥130 mmHg
timeFrame: Baseline to Week 12
measure: Adverse events
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Baotou
country: China
facility: Investigational Site Number 1560039
city: Baotou
country: China
facility: Investigational Site Number 1560040
city: Beijing
country: China
facility: Investigational Site Number 1560001
city: Beijing
country: China
facility: Investigational Site Number 1560038
city: Cangzhou
country: China
facility: Investigational Site Number 1560035
city: Changchun
country: China
facility: Investigational Site Number 1560020
city: Changchun
country: China
facility: Investigational Site Number 1560012
city: Changsha
country: China
facility: Investigational Site Number 1560011
city: Changzhou
country: China
facility: Investigational Site Number 1560021
city: Chongqing
country: China
facility: Investigational Site Number 1560024
city: Dalian
country: China
facility: Investigational Site Number 1560028
city: Dalian
country: China
facility: Investigational Site Number 1560010
city: Dalian
country: China
facility: Investigational Site Number 1560036
city: Fuzhou
country: China
facility: Investigational Site Number 1560030
city: Guangzhou
country: China
facility: Investigational Site Number 1560032
city: Guangzhou
country: China
facility: Investigational Site Number 1560027
city: Hangzhou
country: China
facility: Investigational Site Number 1560041
city: Harbin
country: China
facility: Investigational Site Number 1560046
city: Hefei
country: China
facility: Investigational Site Number 1560009
city: Hohhot
country: China
facility: Investigational Site Number 1560025
city: Huai'An
country: China
facility: Investigational Site Number 1560026
city: Jinan
country: China
facility: Investigational Site Number 1560006
city: Kunming
country: China
facility: Investigational Site Number 1560033
city: Luoyang
country: China
facility: Investigational Site Number 1560034
city: Nanjing
country: China
facility: Investigational Site Number 1560014
city: Pingxiang
country: China
facility: Investigational Site Number 1560018
city: Shanghai
country: China
facility: Investigational Site Number 1560003
city: Shanghai
country: China
facility: Investigational Site Number 1560004
city: Shanghai
country: China
facility: Investigational Site Number 1560013
city: Shenyang
country: China
facility: Investigational Site Number 1560005
city: Shijiazhuang
country: China
facility: Investigational Site Number 1560019
city: Suzhou
country: China
facility: Investigational Site Number 1560017
city: Wuhan
country: China
facility: Investigational Site Number 1560022
city: Wuxi
country: China
facility: Investigational Site Number 1560023
city: Xiangtan
country: China
facility: Investigational Site Number 1560015
city: Yuncheng
country: China
facility: Investigational Site Number 1560043
city: Zhengzhou
country: China
facility: Investigational Site Number 1560042
city: Zhenjiang
country: China
facility: Investigational Site Number 1560007
city: Zhongshan
country: China
facility: Investigational Site Number 1560037
city: Zhuzhou
country: China
facility: Investigational Site Number 1560016
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: