Clinical trial NCT03242018: A Study to Evaluate Safety and Effects of Sotagliflozin 400 and 200 mg on Glucose Control in Participants With Type 2 Diabetes, Severe Impairment of Kidney Function and Inadequate Blood Sugar Control
Official title: A Randomized, Double-blind, Placebo-controlled, 3-arm, Parallel-group 52-week Multicenter Study to Evaluate the Efficacy and Safety of Sotagliflozin in Patients With Type 2 Diabetes Mellitus and Severe Renal Impairment Who Have Inadequate Glycemic Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Chronic Kidney Disease Stage 4
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2017-08-08
Enrollment: 277
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 at Week 26 in participants with Type 2 diabetes who have inadequate glycemic control and severe renal impairment

Secondary Objectives:

* To assess the effects of sotagliflozin 200 mg versus placebo based on change from baseline in HbA1c
* To assess the effects of sotagloflozin 400 mg and 200 mg versus placebo
* To evaluate the safety of sotagliflozin 400 mg and 200 mg versus placebo

Detailed description: The study duration is up to 60 weeks including 4 weeks prior to randomization, 52 weeks of randomized treatment and a visit 4 weeks after completion of the randomized treatment period.

Eligibility criteria: Inclusion criteria :

* Participants with Type 2 Diabetes (drug-naïve or on antidiabetic therapy) and documented severe renal insufficiency - CKD4 - defined by an estimated glomerular filtration rate (eGFR) equation (based on the 4 variable modification of diet in renal disease (MDRD) equation) of ≥15 and \<30 milliliter per minute (mL/min)/1.73 per meter square (m\^2).
* Signed written informed consent to participate in the study in accordance with local regulations.

Exclusion criteria:

* At the time of screening, age \<18 years.
* Hemoglobin A1c (HbA1c) \<7% or \>11%.
* Type 1 diabetes.
* Women of childbearing potential (WOCBP) 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.
* Treatment with an sodium-glucose cotransporter type 2 (SGLT2) inhibitor (canagliflozin, dapagliflozin, empagliflozin) during the last 12 months.
* Uncontrolled high blood pressure, severe anemia, severe cardiovascular problems, such as heart failure, active cancer, or other conditions that the Investigator believes with result in a short life expectancy, 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.

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 HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo
timeFrame: Baseline to Week 26
Secondary outcomes:
measure: Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo
timeFrame: Baseline to Week 26
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
timeFrame: Baseline to Week 26
measure: Change From Baseline in Body Weight at Week 26
timeFrame: Baseline to Week 26
measure: Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg
timeFrame: Baseline to Week 12
measure: Change From Baseline in SBP at Week 12 for All Participants
timeFrame: Baseline to Week 12
measure: Percentage Change From Baseline in the Urine Albumin: Creatinine Ratio (UACR) at Week 26 in Participants With Baseline UACR >30 Milligrams Per Gram (mg/g)
timeFrame: Baseline to Week 26
measure: Percentage of Participants With HbA1c <6.5% at Week 26
timeFrame: Week 26
measure: Percentage of Participants With HbA1c <7.0% at Week 26
timeFrame: Week 26
measure: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: First dose of study drug to last dose of study drug (up to 56.3 weeks) + 4 weeks
Other outcomes:
measure: Percentage of Participants With Hypoglycemic Events
timeFrame: up to 56.3 weeks
Locations:
city: Guntersville
country: United States
facility: Investigational Site Number 8405033
state: Alabama
city: Phoenix
country: United States
facility: Investigational Site Number 8405005
state: Arizona
city: Little Rock
country: United States
facility: Investigational Site Number 8405007
state: Arkansas
city: Chula Vista
country: United States
facility: Investigational Site Number 8405015
state: California
city: La Jolla
country: United States
facility: Investigational Site Number 8405032
state: California
city: Norco
country: United States
facility: Investigational Site Number 8405003
state: California
city: Northridge
country: United States
facility: Investigational Site Number 8405013
state: California
city: San Dimas
country: United States
facility: Investigational Site Number 8405018
state: California
city: Clearwater
country: United States
facility: Investigational Site Number 8405021
state: Florida
city: DeLand
country: United States
facility: Investigational Site Number 8405001
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 8405043
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 8405006
state: Florida
city: Ormond Beach
country: United States
facility: Investigational Site Number 8405025
state: Florida
city: Lawrenceville
country: United States
facility: Investigational Site Number 8405039
state: Georgia
city: Arlington Heights
country: United States
facility: Investigational Site Number 8405041
state: Illinois
city: Sellersburg
country: United States
facility: Investigational Site Number 8405030
state: Indiana
city: Lake Charles
country: United States
facility: Investigational Site Number 8405019
state: Louisiana
city: Flint
country: United States
facility: Investigational Site Number 8405034
state: Michigan
city: Norfolk
country: United States
facility: Investigational Site Number 8405012
state: Nebraska
city: Albany
country: United States
facility: Investigational Site Number 8405035
state: New York
city: Bronx
country: United States
facility: Investigational Site Number 8405014
state: New York
city: Laurelton
country: United States
facility: Investigational Site Number 8405027
state: New York
city: New Bern
country: United States
facility: Investigational Site Number 8405037
state: North Carolina
city: Winston-Salem
country: United States
facility: Investigational Site Number 8405038
state: North Carolina
city: Dayton
country: United States
facility: Investigational Site Number 8405009
state: Ohio
city: Beaumont
country: United States
facility: Investigational Site Number 8405004
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8405036
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8405020
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8405026
state: Texas
city: Hurst
country: United States
facility: Investigational Site Number 8405047
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8405031
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 8405016
state: Texas
city: Layton
country: United States
facility: Investigational Site Number 8405008
state: Utah
city: Winchester
country: United States
facility: Investigational Site Number 8405040
state: Virginia
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 0325001
city: Launs Este
country: Argentina
facility: Investigational Site Number 0325003
city: Mar Del Plata
country: Argentina
facility: Investigational Site Number 0325004
city: Belém
country: Brazil
facility: Investigational Site Number 0765003
city: Fortaleza
country: Brazil
facility: Investigational Site Number 0765001
city: Rio De Janeiro
country: Brazil
facility: Investigational Site Number 0765004
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 0765002
city: Barranquilla
country: Colombia
facility: Investigational Site Number 1705004
city: Bogota
country: Colombia
facility: Investigational Site Number 1705005
city: Manizales
country: Colombia
facility: Investigational Site Number 1705002
city: Zipaquira
country: Colombia
facility: Investigational Site Number 1705001
city: Frankfurt Am Main
country: Germany
facility: Investigational Site Number 2765001
city: Hannover
country: Germany
facility: Investigational Site Number 2765003
city: Münster
country: Germany
facility: Investigational Site Number 2765004
city: Baja
country: Hungary
facility: Investigational Site Number 3485005
city: Debrecen
country: Hungary
facility: Investigational Site Number 3485007
city: Pécs
country: Hungary
facility: Investigational Site Number 3485004
city: Ashkelon
country: Israel
facility: Investigational Site Number 3765002
city: Haifa
country: Israel
facility: Investigational Site Number 3765001
city: Kfar-Saba
country: Israel
facility: Investigational Site Number 3765007
city: Ramat Gan
country: Israel
facility: Investigational Site Number 3765005
city: Rehovot
country: Israel
facility: Investigational Site Number 3765004
city: Tel Aviv
country: Israel
facility: Investigational Site Number 3765003
city: Zefat
country: Israel
facility: Investigational Site Number 3765006
city: Catania
country: Italy
facility: Investigational Site Number 3805003
city: Milano
country: Italy
facility: Investigational Site Number 3805005
city: Napoli
country: Italy
facility: Investigational Site Number 3805006
city: Napoli
country: Italy
facility: Investigational Site Number 3805002
city: Pavia
country: Italy
facility: Investigational Site Number 3805001
city: Roma
country: Italy
facility: Investigational Site Number 3805004
city: Guadalajara Jalisco
country: Mexico
facility: Investigational Site Number 4845007
city: Guadalajara
country: Mexico
facility: Investigational Site Number 4845001
city: Guadalajara
country: Mexico
facility: Investigational Site Number 4845004
city: Merida, Yucatan
country: Mexico
facility: Investigational Site Number 4845008
city: Monterrey, N.L
country: Mexico
facility: Investigational Site Number 4845006
city: Morelia
country: Mexico
facility: Investigational Site Number 4845003
city: Queretaro
country: Mexico
facility: Investigational Site Number 4845002
city: Xalapa
country: Mexico
facility: Investigational Site Number 4845005
city: Krakow
country: Poland
facility: Investigational Site Number 6165003
city: Lodz
country: Poland
facility: Investigational Site Number 6165002
city: Oswiecim
country: Poland
facility: Investigational Site Number 6165004
city: Puławy
country: Poland
facility: Investigational Site Number 6165005
city: Rzeszow
country: Poland
facility: Investigational Site Number 6165001
city: Bacau
country: Romania
facility: Investigational Site Number 6425005
city: Bucuresti
country: Romania
facility: Investigational Site Number 6425002
city: Bucuresti
country: Romania
facility: Investigational Site Number 6425003
city: Hunedoara
country: Romania
facility: Investigational Site Number 6425007
city: Lasi
country: Romania
facility: Investigational Site Number 6425004
city: Targu-Mures
country: Romania
facility: Investigational Site Number 6425001
city: Chelyabinsk
country: Russian Federation
facility: Investigational Site Number 6435004
city: Kemerovo
country: Russian Federation
facility: Investigational Site Number 6435005
city: Krasnodar
country: Russian Federation
facility: Investigational Site Number 6435003
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 6435006
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 6435001
city: Cape Town
country: South Africa
facility: Investigational Site Number 7105003
city: Cape Town
country: South Africa
facility: Investigational Site Number 7105004
city: Johannesburg
country: South Africa
facility: Investigational Site Number 7105001
city: Pretoria
country: South Africa
facility: Investigational Site Number 7105002
city: Barcelona
country: Spain
facility: Investigational Site Number 7245005
city: Barcelona
country: Spain
facility: Investigational Site Number 7245007
city: Ferrol
country: Spain
facility: Investigational Site Number 7245003
city: Granada
country: Spain
facility: Investigational Site Number 7245009
city: Madrid
country: Spain
facility: Investigational Site Number 7245006
city: Málaga
country: Spain
facility: Investigational Site Number 7245004
city: Sevilla
country: Spain
facility: Investigational Site Number 7245001
city: Zaragoza
country: Spain
facility: Investigational Site Number 7245002
city: Chernivtsi
country: Ukraine
facility: Investigational Site Number 8045004
city: Kiev
country: Ukraine
facility: Investigational Site Number 8045006
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8045007
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8045003
city: Kyiv
country: Ukraine
facility: Investigational Site Number 8045001
city: Zaporizhzhia
country: Ukraine
facility: Investigational Site Number 8045002
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Suman Wason, MD
role: STUDY_DIRECTOR
References:
citation: Cherney DZI, Ferrannini E, Umpierrez GE, Peters AL, Rosenstock J, Carroll AK, Lapuerta P, Banks P, Agarwal R. Efficacy and safety of sotagliflozin in patients with type 2 diabetes and severe renal impairment. Diabetes Obes Metab. 2021 Dec;23(12):2632-2642. doi: 10.1111/dom.14513. Epub 2021 Aug 20.