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

Type 2 Diabetes Mellitus Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin Added to a Sulfonylurea Alone or in Combination With Metformin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on a Sulfonylurea Alone or With Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03066830
• Other study ID #: EFC14835
• Secondary ID: 2016-002826-35U1
• Status: Completed
• Phase: Phase 3
• Start date: February 24, 2017
• Est. completion date: April 30, 2019

Study information

• Verified date: April 2021
• Source: Lexicon Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The duration per participants is up to 85 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks and a 2-week single-blind Run-in phase, a 26-week double blind Core Treatment Period, a 53 week double blind Extension, and a 2-week post treatment Follow-up period to collect safety information.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 507
• Est. completion date: April 30, 2019
• Est. primary completion date: April 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• 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.

Exclusion criteria:

• 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.
• Participants is unwilling to perform self-monitoring of blood glucose (SMBG), and complete the participant's diary as required per protocol. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Sotagliflozin (SAR439954)
Pharmaceutical form: tablet Route of administration: oral
• Placebo
Pharmaceutical form: tablet Route of administration: oral
• Metformin
Pharmaceutical form: tablet Route of administration: oral
• Sulfonylurea
Pharmaceutical form: tablet Route of administration: oral

Locations

Country	Name	City	State
Bulgaria	Investigational Site Number 1003003	Plovdiv
Bulgaria	Investigational Site Number 1003002	Ruse
Bulgaria	Investigational Site Number 1003004	Sofia
Estonia	Investigational Site Number 2333003	Parnu
Hungary	Investigational Site Number 3483001	Balatonfüred
Hungary	Investigational Site Number 3483004	Budapest
Hungary	Investigational Site Number 3483006	Budapest
Hungary	Investigational Site Number 3483007	Budapest
Hungary	Investigational Site Number 3483008	Budapest
Hungary	Investigational Site Number 3483010	Budapest
Hungary	Investigational Site Number 3483011	Gyula
Hungary	Investigational Site Number 3483009	Hatvan
Hungary	Investigational Site Number 3483005	Kecskemet
Hungary	Investigational Site Number 3483003	Pécs
Hungary	Investigational Site Number 3483012	Zalaegerszeg
Korea, Republic of	Investigational Site Number 4103001	Goyang-Si, Gyeonggi-Do
Korea, Republic of	Investigational Site Number 4103011	Guri-Si, Gyeonggi-Do
Korea, Republic of	Investigational Site Number 4103003	Seongnam-Si, Gyeonggi-Do
Korea, Republic of	Investigational Site Number 4103005	Seoul
Korea, Republic of	Investigational Site Number 4103006	Seoul
Korea, Republic of	Investigational Site Number 4103007	Seoul
Korea, Republic of	Investigational Site Number 4103010	Seoul
Korea, Republic of	Investigational Site Number 4103009	Wonju-Si, Gangwon-Do
Poland	Investigational Site Number 6163005	Gdansk
Poland	Investigational Site Number 6163006	Gdynia
Poland	Investigational Site Number 6163003	Katowice
Poland	Investigational Site Number 6163002	Poznan
Poland	Investigational Site Number 6163001	Warszawa
Poland	Investigational Site Number 6163004	Wroclaw
Romania	Investigational Site Number 6423004	Bucuresti
Romania	Investigational Site Number 6423002	Iasi
Slovakia	Investigational Site Number 7033001	Bratislava
Slovakia	Investigational Site Number 7033002	Bratislava
Slovakia	Investigational Site Number 7033006	Bratislava
Slovakia	Investigational Site Number 7033004	Malacky
Slovakia	Investigational Site Number 7033003	Sturovo
Slovakia	Investigational Site Number 7033007	Trencin
Ukraine	Investigational Site Number 8043001	Kyiv
Ukraine	Investigational Site Number 8043002	Kyiv
Ukraine	Investigational Site Number 8043003	Kyiv
United Kingdom	Investigational Site Number 8263012	Birmingham
United Kingdom	Investigational Site Number 8263009	Cardiff
United Kingdom	Investigational Site Number 8263007	Glasgow
United Kingdom	Investigational Site Number 8263008	Hexham
United Kingdom	Investigational Site Number 8263003	Inverness
United Kingdom	Investigational Site Number 8263014	Liverpool
United Kingdom	Investigational Site Number 8263011	Manchester
United Kingdom	Investigational Site Number 8263010	Reading
United States	Investigational Site Number 8403029	Bradenton	Florida
United States	Investigational Site Number 8403005	Burke	Virginia
United States	Investigational Site Number 8403002	Dallas	Texas
United States	Investigational Site Number 8403011	Flint	Michigan
United States	Investigational Site Number 8403009	Greenbrae	California
United States	Investigational Site Number 8403028	Greensboro	North Carolina
United States	Investigational Site Number 8403033	Hatboro	Pennsylvania
United States	Investigational Site Number 8403021	Henderson	Nevada
United States	Investigational Site Number 8403022	Houston	Texas
United States	Investigational Site Number 8403012	Huntington Park	California
United States	Investigational Site Number 8403030	Kingsport	Tennessee
United States	Investigational Site Number 8403003	Litchfield Park	Arizona
United States	Investigational Site Number 8403019	Los Angeles	California
United States	Investigational Site Number 8403034	Montclair	California
United States	Investigational Site Number 8403007	Nampa	Idaho
United States	Investigational Site Number 8403004	New Port Richey	Florida
United States	Investigational Site Number 8403020	North Miami Beach	Florida
United States	Investigational Site Number 8403001	Northglenn	Colorado
United States	Investigational Site Number 8403026	Ocoee	Florida
United States	Investigational Site Number 8403032	Orlando	Florida
United States	Investigational Site Number 8403008	Palm Harbor	Florida
United States	Investigational Site Number 8403006	Pembroke Pines	Florida
United States	Investigational Site Number 8403018	Peoria	Arizona
United States	Investigational Site Number 8403013	Port Charlotte	Florida
United States	Investigational Site Number 8403025	Richfield	Minnesota
United States	Investigational Site Number 8403015	Shelby	North Carolina
United States	Investigational Site Number 8403016	Spring Valley	California
United States	Investigational Site Number 8403014	Tustin	California

Sponsors (2)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Bulgaria,  Estonia,  Hungary,  Korea, Republic of,  Poland,  Romania,  Slovakia,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Hypoglycemic Events	Percentage of participants with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia [typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose = 70 mg/dL (3.9 mmol/L)]; Severe [an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions] or documented symptomatic hypoglycemia [typical symptoms of hypoglycemia and plasma glucose = 70 mg/dL]. Participants may be reported in more than one category.	Up to 79 weeks in the treatment period
Primary	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	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26	Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP =130 mmHg	Missing data are imputed using the washout imputation method under the missing, not at random framework. An ANCOVA model was used for the analysis.	Baseline to Week 12
Secondary	Change From Baseline in SBP at Week 12 for All Participants	Missing data are imputed using washout imputation method under the missing not at random framework. An ANCOVA model was used for the analysis.	Baseline to Week 12
Secondary	Change From Baseline in Body Weight at Week 26	Missing data are imputed using the retrieved dropouts imputation method. An ANCOVA model was used for the analysis.	Baseline to Week 26
Secondary	Percentage of Participants With HbA1c <6.5% at Week 26		Week 26
Secondary	Percentage of Participants With HbA1c <7.0% at Week 26		Week 26