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

NCT ID: NCT03242018

Last Updated: 2021-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 277 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-16
• Study Completion Date: 2019-12-11

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.

Conditions

Type 2 Diabetes Mellitus; Chronic Kidney Disease Stage 4

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Following a 2-week run-in phase, participants received two placebo tablets (identical to sotagliflozin 200 milligrams \[mg\] in appearance) orally once daily for up to 56 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.

Sotagliflozin 200 mg

Following a 2-week run-in phase, participants received two tablets, one sotagliflozin 200 mg tablet and one placebo tablet (identical to sotagliflozin 200 mg in appearance), orally once daily for up to 56 weeks.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.

Sotagliflozin

Intervention Type: DRUG

Sotagliflozin 200 mg, tablet, orally, once daily.

Sotagliflozin 400 mg

Following a 2-week run-in phase, participants received sotagliflozin 400 mg, administered as 2 sotagliflozin 200 mg tablets, orally once daily for up to 56 weeks.

Group Type: EXPERIMENTAL

Sotagliflozin

Intervention Type: DRUG

Sotagliflozin 200 mg, tablet, orally, once daily.

Interventions

Placebo

Placebo tablet (identical to sotagliflozin 200 mg in appearance) orally, once daily.

Intervention Type: DRUG

Sotagliflozin

Sotagliflozin 200 mg, tablet, orally, once daily.

Intervention Type: DRUG

Other Intervention Names

SAR439954

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: collaborator

Lexicon Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suman Wason, MD

Role: STUDY_DIRECTOR

Lexicon Pharmaceuticals, Inc.

Locations

Investigational Site Number 8405033

Guntersville, Alabama, United States

Investigational Site Number 8405005

Phoenix, Arizona, United States

Investigational Site Number 8405007

Little Rock, Arkansas, United States

Investigational Site Number 8405015

Chula Vista, California, United States

Investigational Site Number 8405032

La Jolla, California, United States

Investigational Site Number 8405003

Norco, California, United States

Investigational Site Number 8405013

Northridge, California, United States

Investigational Site Number 8405018

San Dimas, California, United States

Investigational Site Number 8405021

Clearwater, Florida, United States

Investigational Site Number 8405001

DeLand, Florida, United States

Investigational Site Number 8405043

Miami, Florida, United States

Investigational Site Number 8405006

Ocoee, Florida, United States

Investigational Site Number 8405025

Ormond Beach, Florida, United States

Investigational Site Number 8405039

Lawrenceville, Georgia, United States

Investigational Site Number 8405041

Arlington Heights, Illinois, United States

Investigational Site Number 8405030

Sellersburg, Indiana, United States

Investigational Site Number 8405019

Lake Charles, Louisiana, United States

Investigational Site Number 8405034

Flint, Michigan, United States

Investigational Site Number 8405012

Norfolk, Nebraska, United States

Investigational Site Number 8405035

Albany, New York, United States

Investigational Site Number 8405027

Laurelton, New York, United States

Investigational Site Number 8405014

The Bronx, New York, United States

Investigational Site Number 8405037

New Bern, North Carolina, United States

Investigational Site Number 8405038

Winston-Salem, North Carolina, United States

Investigational Site Number 8405009

Dayton, Ohio, United States

Investigational Site Number 8405004

Beaumont, Texas, United States

Investigational Site Number 8405036

Dallas, Texas, United States

Investigational Site Number 8405020

Houston, Texas, United States

Investigational Site Number 8405026

Houston, Texas, United States

Investigational Site Number 8405047

Hurst, Texas, United States

Investigational Site Number 8405031

San Antonio, Texas, United States

Investigational Site Number 8405016

San Antonio, Texas, United States

Investigational Site Number 8405008

Layton, Utah, United States

Investigational Site Number 8405040

Winchester, Virginia, United States

Investigational Site Number 0325001

Buenos Aires, , Argentina

Investigational Site Number 0325003

Launs Este, , Argentina

Investigational Site Number 0325004

Mar del Plata, , Argentina

Investigational Site Number 0765003

Belém, , Brazil

Investigational Site Number 0765001

Fortaleza, , Brazil

Investigational Site Number 0765004

Rio de Janeiro, , Brazil

Investigational Site Number 0765002

São Paulo, , Brazil

Investigational Site Number 1705004

Barranquilla, , Colombia

Investigational Site Number 1705005

Bogotá, , Colombia

Investigational Site Number 1705002

Manizales, , Colombia

Investigational Site Number 1705001

Zipaquirá, , Colombia

Investigational Site Number 2765001

Frankfurt am Main, , Germany

Investigational Site Number 2765003

Hanover, , Germany

Investigational Site Number 2765004

Münster, , Germany

Investigational Site Number 3485005

Baja, , Hungary

Investigational Site Number 3485007

Debrecen, , Hungary

Investigational Site Number 3485004

Pécs, , Hungary

Investigational Site Number 3765002

Ashkelon, , Israel

Investigational Site Number 3765001

Haifa, , Israel

Investigational Site Number 3765007

Kfar Saba, , Israel

Investigational Site Number 3765005

Ramat Gan, , Israel

Investigational Site Number 3765004

Rehovot, , Israel

Investigational Site Number 3765006

Safed, , Israel

Investigational Site Number 3765003

Tel Aviv, , Israel

Investigational Site Number 3805003

Catania, , Italy

Investigational Site Number 3805005

Milan, , Italy

Investigational Site Number 3805006

Napoli, , Italy

Investigational Site Number 3805002

Napoli, , Italy

Investigational Site Number 3805001

Pavia, , Italy

Investigational Site Number 3805004

Roma, , Italy

Investigational Site Number 4845001

Guadalajara, , Mexico

Investigational Site Number 4845004

Guadalajara, , Mexico

Investigational Site Number 4845007

Guadalajara Jalisco, , Mexico

Investigational Site Number 4845008

Merida, Yucatan, , Mexico

Investigational Site Number 4845006

Monterrey, N.L, , Mexico

Investigational Site Number 4845003

Morelia, , Mexico

Investigational Site Number 4845002

Querétaro, , Mexico

Investigational Site Number 4845005

Xalapa, , Mexico

Investigational Site Number 6165003

Krakow, , Poland

Investigational Site Number 6165002

Lodz, , Poland

Investigational Site Number 6165004

Oświęcim, , Poland

Investigational Site Number 6165005

Puławy, , Poland

Investigational Site Number 6165001

Rzeszów, , Poland

Investigational Site Number 6425005

Bacau, , Romania

Investigational Site Number 6425002

Bucharest, , Romania

Investigational Site Number 6425003

Bucharest, , Romania

Investigational Site Number 6425007

Hunedoara, , Romania

Investigational Site Number 6425004

Lasi, , Romania

Investigational Site Number 6425001

Târgu Mureş, , Romania

Investigational Site Number 6435004

Chelyabinsk, , Russia

Investigational Site Number 6435005

Kemerovo, , Russia

Investigational Site Number 6435003

Krasnodar, , Russia

Investigational Site Number 6435006

Novosibirsk, , Russia

Investigational Site Number 6435001

Saint Petersburg, , Russia

Investigational Site Number 7105003

Cape Town, , South Africa

Investigational Site Number 7105004

Cape Town, , South Africa

Investigational Site Number 7105001

Johannesburg, , South Africa

Investigational Site Number 7105002

Pretoria, , South Africa

Investigational Site Number 7245005

Barcelona, , Spain

Investigational Site Number 7245007

Barcelona, , Spain

Investigational Site Number 7245003

Ferrol, , Spain

Investigational Site Number 7245009

Granada, , Spain

Investigational Site Number 7245006

Madrid, , Spain

Investigational Site Number 7245004

Málaga, , Spain

Investigational Site Number 7245001

Seville, , Spain

Investigational Site Number 7245002

Zaragoza, , Spain

Investigational Site Number 8045004

Chernivtsi, , Ukraine

Investigational Site Number 8045006

Kiev, , Ukraine

Investigational Site Number 8045007

Kyiv, , Ukraine

Investigational Site Number 8045003

Kyiv, , Ukraine

Investigational Site Number 8045001

Kyiv, , Ukraine

Investigational Site Number 8045002

Zaporizhzhia, , Ukraine

Countries

United States; Argentina; Brazil; Colombia; Germany; Hungary; Israel; Italy; Mexico; Poland; Romania; Russia; South Africa; Spain; Ukraine

References

Natale P, Tunnicliffe DJ, Toyama T, Palmer SC, Saglimbene VM, Ruospo M, Gargano L, Stallone G, Gesualdo L, Strippoli GF. Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2024 May 21;5(5):CD015588. doi: 10.1002/14651858.CD015588.pub2.

Reference Type: DERIVED

PMID: 38770818 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34338408 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004906-32

Identifier Type: -

Identifier Source: secondary_id

U1111-1190-7589

Identifier Type: OTHER

Identifier Source: secondary_id

EFC15166

Identifier Type: -

Identifier Source: org_study_id