Efficacy and Safety of Sotagliflozin Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control While Taking Insulin Alone or With Other Oral Antidiabetic Agents

Type 2 Diabetes Mellitus Clinical Trial

— SOTA-INS  

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel-group, 52-week Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin in Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Basal Insulin Alone or in Addition to Oral Antidiabetes Drugs (OADs)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03285594
• Other study ID #: EFC14868
• Secondary ID: 2016-001804-43U1
• Status: Completed
• Phase: Phase 3
• Start date: September 15, 2017
• Est. completion date: September 27, 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 with respect to hemoglobin A1C (HbA1c) reduction in participants with type 2 diabetes mellitus (T2D) who have inadequate glycemic control on basal insulin alone or with oral antidiabetes drugs (OADs).

Secondary Objectives:

• To assess the effects of sotagliflozin 400 mg versus placebo on fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), and HbA1c.

• To assess the effects of sotagliflozin 200 mg versus placebo on HbA1c, body weight, FPG, and SBP.

• To evaluate the safety of sotagliflozin 400 and 200 mg versus placebo.

Description:

Up to 60 weeks (Screening phase of up to 2 weeks, a 4-week Lantus titration/single-blind placebo Run-in phase), a 52-week double blind Treatment Period, and a 2-week post-treatment Follow-up Period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 571
• Est. completion date: September 27, 2019
• Est. primary completion date: September 17, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria :

• Participants with Type 2 Diabetes Mellitus (T2DM) using any types of basal insulin alone or in combination with up to 2 OADs.

• Participants have given written informed consent to participate in the study in accordance with local regulations.

Exclusion criteria:

• At the time of Screening age <18 years or <legal age of majority, whichever is greater.

• Type 1 diabetes mellitus.

• Oral antidiabetic drugs dose not stable for 8 weeks before Screening.

• Use of basal insulin therapy (e.g., insulin glargine, Neutral Protamine Hagedorn (NPH), detemir, or degludec) for less than 6 months before Screening.

• Dose of basal insulin (e.g., insulin glargine, NPH, detemir, or degludec) not stable for 8 weeks before Screening (i.e., total daily insulin dose increased or decreased by more than 20%).

• Known unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema that is likely to require laser, surgical treatment during study period.

• Use of injectable diabetes drugs other than basal insulin (e.g., insulin glargine, NPH, detemir, or degludec), i.e., prandial or rapid-acting insulins, short-acting insulins, glucagon-like peptide 1 (GLP-1) receptor agonists, or inhaled prandial insulin (Afrezza) within 8 weeks of Screening.

• Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor (e.g., canagliflozin, dapagliflozin, or empagliflozin) within 3 months prior to the trial.

• Use of systemic glucocorticoids (excluding topical, intra articular, or ophthalmic application, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit.

• Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease that, according to the Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult.

• Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at Randomization.

• Known presence of factors that interfere with the Central Lab HbA1c measurement (e.g., genetic hemoglobin (Hb) variants) compromising the reliability of HbA1c assessment or medical conditions that affect interpretation of HbA1c results (e.g., blood transfusion or severe blood loss in the last 3 months prior to randomization, any condition that shortens erythrocyte survival).

• Participants who has taken other investigational drugs or prohibited therapy for this study within 12 weeks or 5 half-lives from prior to Screening, whichever is longer.

• Participants unwilling 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.

• HbA1c <7.5% or HbA1c >10.5% measured by the central laboratory at Screening.

• HbA1c <7% measured by the central laboratory at Visit 5 (Week -1).

• History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit.

• Pregnant (confirmed by serum pregnancy test at Screening) or breastfeeding women.

• 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.

• Mean of 3 separate blood pressure measurements >180 mmHg (systolic blood pressure [SBP]) or >100 mmHg (diastolic blood pressure [DBP]).

• History of gastric surgery including history of gastric banding or inflammatory bowel disease within 3 years prior to the Screening Visit.

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of the normal laboratory range

• Total bilirubin >1.5 times the upper limit of the normal laboratory range (except in case of Gilbert's syndrome).

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
Pharmaceutical form: Tablet Route of administration: Oral
• Insulin glargine (HOE901)
Pharmaceutical form: Solution Route of administration: Subcutaneous
• Placebo
Pharmaceutical form: Tablet Route of administration: Oral
• Oral Antidiabetes Drugs (OADs)
OADs (including metformin) as prescribed by the investigator as per local labeling.

Locations

Country	Name	City	State
Bulgaria	Investigational Site Number 1006009	Gabrovo
Bulgaria	Investigational Site Number 1006003	Plovdiv
Bulgaria	Investigational Site Number 1006001	Ruse
Bulgaria	Investigational Site Number 1006004	Ruse
Bulgaria	Investigational Site Number 1006006	Smolyan
Bulgaria	Investigational Site Number 1006002	Sofia
Bulgaria	Investigational Site Number 1006010	Sofia
Bulgaria	Investigational Site Number 1006005	Stara Zagora
Bulgaria	Investigational Site Number 1006007	Varna
Canada	Investigational Site Number 1246003	Brampton
Canada	Investigational Site Number 1246005	Burlington
Canada	Investigational Site Number 1246004	Etobicoke
Canada	Investigational Site Number 1246002	Toronto
Canada	Investigational Site Number 1246001	Vancouver
Czechia	Investigational Site Number 2036003	Holesov
Czechia	Investigational Site Number 2036002	Krnov
Czechia	Investigational Site Number 2036001	Olomouc
Czechia	Investigational Site Number 2036005	Ostrava
Czechia	Investigational Site Number 2036006	Praha 10 - Uhrineves
Czechia	Investigational Site Number 2036007	Praha 4
Czechia	Investigational Site Number 2036008	Praha 4
France	Investigational Site Number 2506008	Besançon Cedex
France	Investigational Site Number 2506003	Corbeil-Essonnes
France	Investigational Site Number 2506005	Dijon
France	Investigational Site Number 2506012	Mulhouse
France	Investigational Site Number 2506004	Nantes
France	Investigational Site Number 2506007	Narbonne
France	Investigational Site Number 2506006	Paris
France	Investigational Site Number 2506010	Pierre-Benite
France	Investigational Site Number 2506009	Poitiers
France	Investigational Site Number 2506011	Saint-Mande
France	Investigational Site Number 2506002	Vénissieux
Hungary	Investigational Site Number 3486002	Budapest
Hungary	Investigational Site Number 3486007	Budapest
Hungary	Investigational Site Number 3486006	Hatvan
Hungary	Investigational Site Number 3486009	Kecskemet
Hungary	Investigational Site Number 3486003	Komarom
Hungary	Investigational Site Number 3486005	Nyíregyháza
Hungary	Investigational Site Number 3486001	Pécs
Hungary	Investigational Site Number 3486008	Zalaegerszeg
Slovakia	Investigational Site Number 7036004	Bardejov
Slovakia	Investigational Site Number 7036001	Bratislava
Slovakia	Investigational Site Number 7036008	Bratislava
Slovakia	Investigational Site Number 7036003	Kosice
Slovakia	Investigational Site Number 7036010	Kosice
Slovakia	Investigational Site Number 7036007	Levice
Slovakia	Investigational Site Number 7036009	Levice
Slovakia	Investigational Site Number 7036011	Lucenec
Slovakia	Investigational Site Number 7036006	Nitra
Slovakia	Investigational Site Number 7036005	Sabinov
United Kingdom	Investigational Site Number 8266002	Darlington
United Kingdom	Investigational Site Number 8266006	Doncaster
United Kingdom	Investigational Site Number 8266008	Dundee
United Kingdom	Investigational Site Number 8266001	Leicester
United Kingdom	Investigational Site Number 8266004	London
United Kingdom	Investigational Site Number 8266003	Salford
United States	Investigational Site Number 8406034	Asheville	North Carolina
United States	Investigational Site Number 8406031	Beachwood	Ohio
United States	Investigational Site Number 8406046	Chapel Hill	North Carolina
United States	Investigational Site Number 8406026	Charlotte	North Carolina
United States	Investigational Site Number 8406009	Chattanooga	Tennessee
United States	Investigational Site Number 8406027	Chicago	Illinois
United States	Investigational Site Number 8406054	Chicago	Illinois
United States	Investigational Site Number 8406023	Columbus	Ohio
United States	Investigational Site Number 8406043	Coral Gables	Florida
United States	Investigational Site Number 8406017	Dallas	Texas
United States	Investigational Site Number 8406047	Dallas	Texas
United States	Investigational Site Number 8406008	DeLand	Florida
United States	Investigational Site Number 8406016	Detroit	Michigan
United States	Investigational Site Number 8406005	Dublin	Ohio
United States	Investigational Site Number 8406042	Evansville	Indiana
United States	Investigational Site Number 8406038	Greenville	North Carolina
United States	Investigational Site Number 8406036	Hickory	North Carolina
United States	Investigational Site Number 8406037	Houston	Texas
United States	Investigational Site Number 8406048	Houston	Texas
United States	Investigational Site Number 8406006	Huntington Park	California
United States	Investigational Site Number 8406053	Lincoln	California
United States	Investigational Site Number 8406040	Los Angeles	California
United States	Investigational Site Number 8406030	Maitland	Florida
United States	Investigational Site Number 8406039	McAllen	Texas
United States	Investigational Site Number 8406004	Mentor	Ohio
United States	Investigational Site Number 8406028	Mesa	Arizona
United States	Investigational Site Number 8406032	Moncks Corner	South Carolina
United States	Investigational Site Number 8406044	New Orleans	Louisiana
United States	Investigational Site Number 8406051	New Orleans	Louisiana
United States	Investigational Site Number 8406003	New Port Richey	Florida
United States	Investigational Site Number 8406018	New York	New York
United States	Investigational Site Number 8406029	North Miami Beach	Florida
United States	Investigational Site Number 8406052	Ocoee	Florida
United States	Investigational Site Number 8406033	Oklahoma City	Oklahoma
United States	Investigational Site Number 8406010	Papillion	Nebraska
United States	Investigational Site Number 8406013	Phoenix	Arizona
United States	Investigational Site Number 8406020	Phoenix	Arizona
United States	Investigational Site Number 8406001	Port Charlotte	Florida
United States	Investigational Site Number 8406024	Rockville	Maryland
United States	Investigational Site Number 8406011	Saint Louis	Missouri
United States	Investigational Site Number 8406022	Saint Petersburg	Florida
United States	Investigational Site Number 8406035	Salt Lake City	Utah
United States	Investigational Site Number 8406050	San Antonio	Texas
United States	Investigational Site Number 8406045	Seymour	Tennessee
United States	Investigational Site Number 8406021	Shavano Park	Texas
United States	Investigational Site Number 8406025	Tampa	Florida
United States	Investigational Site Number 8406014	West Jordan	Utah
United States	Investigational Site Number 8406002	West Palm Beach	Florida
United States	Investigational Site Number 8406015	Wilmington	North Carolina
United States	Investigational Site Number 8406019	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Lexicon Pharmaceuticals	Sanofi

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Czechia,  France,  Hungary,  Slovakia,  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].	Up to 55.7 weeks
Primary	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18	An analysis of covariance (ANCOVA) model was used for the analysis.	Baseline and Week 18
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18	FPG was performed in fasting state, that is, without any food intake (except for water) for at least 8 hours. An ANCOVA model was used for the analysis.	Baseline and Week 18
Secondary	Change From Baseline in Body Weight at Week 18	An ANCOVA model was used for the analysis.	Baseline and Week 18
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP =130 mmHg at Week 12	An ANCOVA model was used for the analysis. Here, N is the number of participants with data available at a given time point.	Baseline and Week 12
Secondary	Change From Baseline in SBP at Week 12 for All Participants	An ANCOVA model was used for the analysis.	Baseline to Week 12
Secondary	Change From Baseline in HbA1c at Week 52	An ANCOVA model was used for the analysis.	Baseline and Week 52
Secondary	Change From Baseline in Body Weight at Week 52	An ANCOVA model was used for the analysis.	Baseline and Week 52
Secondary	Percentage of Participants With Adverse Events (AEs)	An AE is any untoward medical occurrence in a participants or clinical investigation participants administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 weeks