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

NCT03242018 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC151662016-004906-32U1111-1190-7589
• Study Type: interventional
• Target: 277
• Locations: 15 countries
• Sites: 106

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

Conditions

Type 2 Diabetes Mellitus; Chronic Kidney Disease Stage 4

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 400 mg Versus Placebo

  An analysis of covariance (ANCOVA) model was used for the analysis.

  Baseline to Week 26

Secondary Outcomes (9)

• Change From Baseline in HbA1c at Week 26 Comparing Sotagliflozin 200 mg Versus Placebo

  Baseline to Week 26

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26

  Baseline to Week 26

• Change From Baseline in Body Weight at Week 26

  Baseline to Week 26

• Change From Baseline in SBP at Week 12 in Participants With Baseline SBP ≥130 mmHg

  Baseline to Week 12

• Change From Baseline in SBP at Week 12 for All Participants

  Baseline to Week 12

Other Outcomes (1)

• Percentage of Participants With Hypoglycemic Events

  up to 56.3 weeks

Study Arms (3)

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Sotagliflozin 200 mg

EXPERIMENTAL

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.

Drug: Placebo; Drug: Sotagliflozin

Sotagliflozin 400 mg

EXPERIMENTAL

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.

Drug: Sotagliflozin

Interventions

Placebo DRUG

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

Placebo; Sotagliflozin 200 mg

Sotagliflozin DRUG

Sotagliflozin 200 mg, tablet, orally, once daily.

Also known as: SAR439954

Sotagliflozin 200 mg; Sotagliflozin 400 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (106)

Investigational Site Number 8405033

Guntersville, Alabama, 35976-2206, United States

Location

Investigational Site Number 8405005

Phoenix, Arizona, 85018-2701, United States

Location

Investigational Site Number 8405007

Little Rock, Arkansas, 72205, United States

Location

Investigational Site Number 8405015

Chula Vista, California, 91910, United States

Location

Investigational Site Number 8405032

La Jolla, California, 92037, United States

Location

Investigational Site Number 8405003

Norco, California, 92860-3611, United States

Location

Investigational Site Number 8405013

Northridge, California, 91324, United States

Location

Investigational Site Number 8405018

San Dimas, California, 91773, United States

Location

Investigational Site Number 8405021

Clearwater, Florida, 33761-2022, United States

Location

Investigational Site Number 8405001

DeLand, Florida, 32720-0834, United States

Location

Investigational Site Number 8405043

Miami, Florida, 33155-4630, United States

Location

Investigational Site Number 8405006

Ocoee, Florida, 34761-4547, United States

Location

Investigational Site Number 8405025

Ormond Beach, Florida, 32174-8187, United States

Location

Investigational Site Number 8405039

Lawrenceville, Georgia, 30046, United States

Location

Investigational Site Number 8405041

Arlington Heights, Illinois, 60005-4197, United States

Location

Investigational Site Number 8405030

Sellersburg, Indiana, 47172-8932, United States

Location

Investigational Site Number 8405019

Lake Charles, Louisiana, 70601, United States

Location

Investigational Site Number 8405034

Flint, Michigan, 48532-3447, United States

Location

Investigational Site Number 8405012

Norfolk, Nebraska, 68701-2669, United States

Location

Investigational Site Number 8405035

Albany, New York, 12206, United States

Location

Investigational Site Number 8405027

Laurelton, New York, 11413, United States

Location

Investigational Site Number 8405014

The Bronx, New York, 10455, United States

Location

Investigational Site Number 8405037

New Bern, North Carolina, 28562-5200, United States

Location

Investigational Site Number 8405038

Winston-Salem, North Carolina, 27103, United States

Location

Investigational Site Number 8405009

Dayton, Ohio, 45419-4336, United States

Location

Investigational Site Number 8405004

Beaumont, Texas, 77702, United States

Location

Investigational Site Number 8405036

Dallas, Texas, 75208, United States

Location

Investigational Site Number 8405020

Houston, Texas, 77058, United States

Location

Investigational Site Number 8405026

Houston, Texas, 77099-4307, United States

Location

Investigational Site Number 8405047

Hurst, Texas, 76054, United States

Location

Investigational Site Number 8405031

San Antonio, Texas, 78215, United States

Location

Investigational Site Number 8405016

San Antonio, Texas, 78249-2782, United States

Location

Investigational Site Number 8405008

Layton, Utah, 84041-1200, United States

Location

Investigational Site Number 8405040

Winchester, Virginia, 22601, United States

Location

Investigational Site Number 0325001

Buenos Aires, C1425DES, Argentina

Location

Investigational Site Number 0325003

Launs Este, B1824KAJ, Argentina

Location

Investigational Site Number 0325004

Mar del Plata, B7600, Argentina

Location

Investigational Site Number 0765003

Belém, 66073-005, Brazil

Location

Investigational Site Number 0765001

Fortaleza, 60170-195, Brazil

Location

Investigational Site Number 0765004

Rio de Janeiro, 22271-100, Brazil

Location

Investigational Site Number 0765002

São Paulo, 01244-030, Brazil

Location

Investigational Site Number 1705004

Barranquilla, 80020, Colombia

Location

Investigational Site Number 1705005

Bogotá, 110221, Colombia

Location

Investigational Site Number 1705002

Manizales, 170004, Colombia

Location

Investigational Site Number 1705001

Zipaquirá, 250252, Colombia

Location

Investigational Site Number 2765001

Frankfurt am Main, 60596, Germany

Location

Investigational Site Number 2765003

Hanover, 30625, Germany

Location

Investigational Site Number 2765004

Münster, 48145, Germany

Location

Investigational Site Number 3485005

Baja, 6500, Hungary

Location

Investigational Site Number 3485007

Debrecen, 4032, Hungary

Location

Investigational Site Number 3485004

Pécs, 7624, Hungary

Location

Investigational Site Number 3765002

Ashkelon, 78278, Israel

Location

Investigational Site Number 3765001

Haifa, 31096, Israel

Location

Investigational Site Number 3765007

Kfar Saba, 44281, Israel

Location

Investigational Site Number 3765005

Ramat Gan, 52621, Israel

Location

Investigational Site Number 3765004

Rehovot, 7642001, Israel

Location

Investigational Site Number 3765006

Safed, 13100, Israel

Location

Investigational Site Number 3765003

Tel Aviv, 61480, Israel

Location

Investigational Site Number 3805003

Catania, 95123, Italy

Location

Investigational Site Number 3805005

Milan, 20132, Italy

Location

Investigational Site Number 3805006

Napoli, 00181, Italy

Location

Investigational Site Number 3805002

Napoli, 80138, Italy

Location

Investigational Site Number 3805001

Pavia, 27100, Italy

Location

Investigational Site Number 3805004

Roma, 00168, Italy

Location

Investigational Site Number 4845001

Guadalajara, 44210, Mexico

Location

Investigational Site Number 4845004

Guadalajara, 44600, Mexico

Location

Investigational Site Number 4845007

Guadalajara Jalisco, 44130, Mexico

Location

Investigational Site Number 4845008

Merida, Yucatan, 97130, Mexico

Location

Investigational Site Number 4845006

Monterrey, N.L, 64460, Mexico

Location

Investigational Site Number 4845003

Morelia, 58260, Mexico

Location

Investigational Site Number 4845002

Querétaro, 76000, Mexico

Location

Investigational Site Number 4845005

Xalapa, 91020, Mexico

Location

Investigational Site Number 6165003

Krakow, 31-209, Poland

Location

Investigational Site Number 6165002

Lodz, 92-213, Poland

Location

Investigational Site Number 6165004

Oświęcim, 32-600, Poland

Location

Investigational Site Number 6165005

Puławy, 24-100, Poland

Location

Investigational Site Number 6165001

Rzeszów, 35-055, Poland

Location

Investigational Site Number 6425005

Bacau, 600238, Romania

Location

Investigational Site Number 6425002

Bucharest, 010825, Romania

Location

Investigational Site Number 6425003

Bucharest, 020475, Romania

Location

Investigational Site Number 6425007

Hunedoara, 331057, Romania

Location

Investigational Site Number 6425004

Lasi, 700503, Romania

Location

Investigational Site Number 6425001

Târgu Mureş, 540142, Romania

Location

Investigational Site Number 6435004

Chelyabinsk, 4540, Russia

Location

Investigational Site Number 6435005

Kemerovo, 650002, Russia

Location

Investigational Site Number 6435003

Krasnodar, 350032, Russia

Location

Investigational Site Number 6435006

Novosibirsk, 630091, Russia

Location

Investigational Site Number 6435001

Saint Petersburg, 194358, Russia

Location

Investigational Site Number 7105003

Cape Town, 7505, South Africa

Location

Investigational Site Number 7105004

Cape Town, 7570, South Africa

Location

Investigational Site Number 7105001

Johannesburg, 2188, South Africa

Location

Investigational Site Number 7105002

Pretoria, 0002, South Africa

Location

Investigational Site Number 7245005

Barcelona, 08035, Spain

Location

Investigational Site Number 7245007

Barcelona, 08036, Spain

Location

Investigational Site Number 7245003

Ferrol, 15405, Spain

Location

Investigational Site Number 7245009

Granada, 18012, Spain

Location

Investigational Site Number 7245006

Madrid, 28041, Spain

Location

Investigational Site Number 7245004

Málaga, 29010, Spain

Location

Investigational Site Number 7245001

Seville, 41009, Spain

Location

Investigational Site Number 7245002

Zaragoza, 50009, Spain

Location

Investigational Site Number 8045004

Chernivtsi, 58022, Ukraine

Location

Investigational Site Number 8045006

Kiev, 02002, Ukraine

Location

Investigational Site Number 8045007

Kyiv, 02091, Ukraine

Location

Investigational Site Number 8045003

Kyiv, 04050, Ukraine

Location

Investigational Site Number 8045001

Kyiv, 3037, Ukraine

Location

Investigational Site Number 8045002

Zaporizhzhia, 69600, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 38770818 DERIVED

• 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.

  PMID: 34338408 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic

Interventions

(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Medical Affairs
• Organization: Lexicon Pharmaceuticals, Inc.

medical-information@lexpharma.com

(510) 338-6064

Study Officials

• Suman Wason, MD

  Lexicon Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 3, 2017
• First Posted: August 8, 2017
• Study Start: August 16, 2017
• Primary Completion: May 16, 2019
• Study Completion: December 11, 2019
• Last Updated: June 25, 2021
• Results First Posted: June 25, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

PL (5); IT (6); HU (3); RU (5); ES (8); BR (4); ME (8); RO (6); ZA (4); UA (6); DE (3); IL (7); CO (4); AR (3); US (34)