Clinical trial NCT03285594: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-09-18
Enrollment: 571
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 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Hemoglobin A1c (HbA1c) at Week 18
timeFrame: Baseline and Week 18
Secondary outcomes:
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 18
timeFrame: Baseline and Week 18
measure: Change From Baseline in Body Weight at Week 18
timeFrame: Baseline and Week 18
measure: Change From Baseline in Systolic Blood Pressure (SBP) for Participants With Baseline SBP ≥130 mmHg at Week 12
timeFrame: Baseline and Week 12
measure: Change From Baseline in SBP at Week 12 for All Participants
timeFrame: Baseline to Week 12
measure: Change From Baseline in HbA1c at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Body Weight at Week 52
timeFrame: Baseline and Week 52
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: First dose of study drug to last dose of study drug (up to 55.7 weeks) + 2 weeks
Other outcomes:
measure: Percentage of Participants With Hypoglycemic Events
timeFrame: Up to 55.7 weeks
Locations:
city: Mesa
country: United States
facility: Investigational Site Number 8406028
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 8406013
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 8406020
state: Arizona
city: Huntington Park
country: United States
facility: Investigational Site Number 8406006
state: California
city: Lincoln
country: United States
facility: Investigational Site Number 8406053
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8406040
state: California
city: Coral Gables
country: United States
facility: Investigational Site Number 8406043
state: Florida
city: DeLand
country: United States
facility: Investigational Site Number 8406008
state: Florida
city: Maitland
country: United States
facility: Investigational Site Number 8406030
state: Florida
city: New Port Richey
country: United States
facility: Investigational Site Number 8406003
state: Florida
city: North Miami Beach
country: United States
facility: Investigational Site Number 8406029
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 8406052
state: Florida
city: Port Charlotte
country: United States
facility: Investigational Site Number 8406001
state: Florida
city: Saint Petersburg
country: United States
facility: Investigational Site Number 8406022
state: Florida
city: Tampa
country: United States
facility: Investigational Site Number 8406025
state: Florida
city: West Palm Beach
country: United States
facility: Investigational Site Number 8406002
state: Florida
city: Chicago
country: United States
facility: Investigational Site Number 8406054
state: Illinois
city: Chicago
country: United States
facility: Investigational Site Number 8406027
state: Illinois
city: Evansville
country: United States
facility: Investigational Site Number 8406042
state: Indiana
city: New Orleans
country: United States
facility: Investigational Site Number 8406044
state: Louisiana
city: New Orleans
country: United States
facility: Investigational Site Number 8406051
state: Louisiana
city: Rockville
country: United States
facility: Investigational Site Number 8406024
state: Maryland
city: Detroit
country: United States
facility: Investigational Site Number 8406016
state: Michigan
city: Saint Louis
country: United States
facility: Investigational Site Number 8406011
state: Missouri
city: Papillion
country: United States
facility: Investigational Site Number 8406010
state: Nebraska
city: New York
country: United States
facility: Investigational Site Number 8406018
state: New York
city: Asheville
country: United States
facility: Investigational Site Number 8406034
state: North Carolina
city: Chapel Hill
country: United States
facility: Investigational Site Number 8406046
state: North Carolina
city: Charlotte
country: United States
facility: Investigational Site Number 8406026
state: North Carolina
city: Greenville
country: United States
facility: Investigational Site Number 8406038
state: North Carolina
city: Hickory
country: United States
facility: Investigational Site Number 8406036
state: North Carolina
city: Wilmington
country: United States
facility: Investigational Site Number 8406015
state: North Carolina
city: Winston-Salem
country: United States
facility: Investigational Site Number 8406019
state: North Carolina
city: Beachwood
country: United States
facility: Investigational Site Number 8406031
state: Ohio
city: Columbus
country: United States
facility: Investigational Site Number 8406023
state: Ohio
city: Dublin
country: United States
facility: Investigational Site Number 8406005
state: Ohio
city: Mentor
country: United States
facility: Investigational Site Number 8406004
state: Ohio
city: Oklahoma City
country: United States
facility: Investigational Site Number 8406033
state: Oklahoma
city: Moncks Corner
country: United States
facility: Investigational Site Number 8406032
state: South Carolina
city: Chattanooga
country: United States
facility: Investigational Site Number 8406009
state: Tennessee
city: Seymour
country: United States
facility: Investigational Site Number 8406045
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site Number 8406047
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8406017
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8406048
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8406037
state: Texas
city: McAllen
country: United States
facility: Investigational Site Number 8406039
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8406050
state: Texas
city: Shavano Park
country: United States
facility: Investigational Site Number 8406021
state: Texas
city: Salt Lake City
country: United States
facility: Investigational Site Number 8406035
state: Utah
city: West Jordan
country: United States
facility: Investigational Site Number 8406014
state: Utah
city: Gabrovo
country: Bulgaria
facility: Investigational Site Number 1006009
city: Plovdiv
country: Bulgaria
facility: Investigational Site Number 1006003
city: Ruse
country: Bulgaria
facility: Investigational Site Number 1006004
city: Ruse
country: Bulgaria
facility: Investigational Site Number 1006001
city: Smolyan
country: Bulgaria
facility: Investigational Site Number 1006006
city: Sofia
country: Bulgaria
facility: Investigational Site Number 1006002
city: Sofia
country: Bulgaria
facility: Investigational Site Number 1006010
city: Stara Zagora
country: Bulgaria
facility: Investigational Site Number 1006005
city: Varna
country: Bulgaria
facility: Investigational Site Number 1006007
city: Brampton
country: Canada
facility: Investigational Site Number 1246003
city: Burlington
country: Canada
facility: Investigational Site Number 1246005
city: Etobicoke
country: Canada
facility: Investigational Site Number 1246004
city: Toronto
country: Canada
facility: Investigational Site Number 1246002
city: Vancouver
country: Canada
facility: Investigational Site Number 1246001
city: Holesov
country: Czechia
facility: Investigational Site Number 2036003
city: Krnov
country: Czechia
facility: Investigational Site Number 2036002
city: Olomouc
country: Czechia
facility: Investigational Site Number 2036001
city: Ostrava
country: Czechia
facility: Investigational Site Number 2036005
city: Praha 10 - Uhrineves
country: Czechia
facility: Investigational Site Number 2036006
city: Praha 4
country: Czechia
facility: Investigational Site Number 2036007
city: Praha 4
country: Czechia
facility: Investigational Site Number 2036008
city: Besançon Cedex
country: France
facility: Investigational Site Number 2506008
city: Corbeil-Essonnes
country: France
facility: Investigational Site Number 2506003
city: Dijon
country: France
facility: Investigational Site Number 2506005
city: Mulhouse
country: France
facility: Investigational Site Number 2506012
city: Nantes
country: France
facility: Investigational Site Number 2506004
city: Narbonne
country: France
facility: Investigational Site Number 2506007
city: Paris
country: France
facility: Investigational Site Number 2506006
city: Pierre-Benite
country: France
facility: Investigational Site Number 2506010
city: Poitiers
country: France
facility: Investigational Site Number 2506009
city: Saint-Mande
country: France
facility: Investigational Site Number 2506011
city: Vénissieux
country: France
facility: Investigational Site Number 2506002
city: Budapest
country: Hungary
facility: Investigational Site Number 3486007
city: Budapest
country: Hungary
facility: Investigational Site Number 3486002
city: Hatvan
country: Hungary
facility: Investigational Site Number 3486006
city: Kecskemet
country: Hungary
facility: Investigational Site Number 3486009
city: Komarom
country: Hungary
facility: Investigational Site Number 3486003
city: Nyíregyháza
country: Hungary
facility: Investigational Site Number 3486005
city: Pécs
country: Hungary
facility: Investigational Site Number 3486001
city: Zalaegerszeg
country: Hungary
facility: Investigational Site Number 3486008
city: Bardejov
country: Slovakia
facility: Investigational Site Number 7036004
city: Bratislava
country: Slovakia
facility: Investigational Site Number 7036008
city: Bratislava
country: Slovakia
facility: Investigational Site Number 7036001
city: Kosice
country: Slovakia
facility: Investigational Site Number 7036010
city: Kosice
country: Slovakia
facility: Investigational Site Number 7036003
city: Levice
country: Slovakia
facility: Investigational Site Number 7036007
city: Levice
country: Slovakia
facility: Investigational Site Number 7036009
city: Lucenec
country: Slovakia
facility: Investigational Site Number 7036011
city: Nitra
country: Slovakia
facility: Investigational Site Number 7036006
city: Sabinov
country: Slovakia
facility: Investigational Site Number 7036005
city: Darlington
country: United Kingdom
facility: Investigational Site Number 8266002
city: Doncaster
country: United Kingdom
facility: Investigational Site Number 8266006
city: Dundee
country: United Kingdom
facility: Investigational Site Number 8266008
city: Leicester
country: United Kingdom
facility: Investigational Site Number 8266001
city: London
country: United Kingdom
facility: Investigational Site Number 8266004
city: Salford
country: United Kingdom
facility: Investigational Site Number 8266003
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Suman Wason, MD
role: STUDY_DIRECTOR
References: