Efficacy, Safety, and Tolerability Study of Sotagliflozin as Adjunct Therapy in Adult Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy

NCT02421510 | Completed Phase 3 Results DMC

• 3 other identifiers: LX4211.1-310-T1DMLX4211.3102014-005153-39
• Study Type: interventional
• Target: 782
• Locations: 17 countries
• Sites: 96

Brief Summary

This Phase 3 study was intended to demonstrate superiority of either Sotagliflozin high dose or low dose versus placebo on glycosylated hemoglobin A1C (A1C) reduction at Week 24 when used as an adjunct in adult participants with type 1 diabetes mellitus (T1D) who have inadequate glycemic control with insulin therapy.

Conditions

Type 1 Diabetes Mellitus

Keywords

High level of sugar (glucose) in the blood

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in A1C at Week 24

  Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. Least square (LS) means were obtained from a mixed-effects model for repeated measures (MMRM) that included fixed, categorical effects of treatment, randomization strata of insulin delivery method (MDI, CSII), randomization strata of Week -2 A1C (\<= 8.5%, \>8.5%), time (study week), a treatment-by-time interaction, and baseline A1C-by-time interaction as a covariate. A negative change from baseline (a reduction of A1C value at Week 24) indicates an improvement.

  Baseline to Week 24

Secondary Outcomes (7)

• Percentage of Participants With A1C <7.0% at Week 24 and no Episode of Severe Hypoglycemia, and no Episode of Diabetic Ketoacidosis (DKA) From Baseline to Week 24

  Baseline to Week 24

• Change From Baseline in Body Weight at Week 24

  Baseline to Week 24

• Change From Baseline in Mean Daily Bolus Insulin Dose at Week 24

  Baseline to Week 24

• Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24

  Baseline to Week 24

• Change From Baseline in Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score at Week 24

  Baseline to Week 24

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.

Drug: Placebo

Sotagliflozin 200 mg

EXPERIMENTAL

Sotagliflozin 200 milligram (mg) (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.

Drug: Sotagliflozin

Sotagliflozin 400 mg

EXPERIMENTAL

Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.

Drug: Sotagliflozin

Interventions

Sotagliflozin DRUG

High dose Sotagliflozin, once daily, before the first meal of the day

Sotagliflozin 400 mg

Placebo DRUG

Placebo, once daily, before the first meal of the day

Placebo

Eligibility Criteria

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

You may qualify if:

• Participant who gave written informed consent to participate in the study in accordance with local regulations.
• Adult participants 18 years and older with a diagnosis of T1D made at least 1 year prior to informed consent.
• Participants treated with insulin or insulin analog delivered via continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).
• Willing and were able to perform Self-monitoring of blood glucose (SMBG) and completed the study diary as required per protocol.
• At the Screening Visit, A1C was between 7.0% to 11.0%.
• Females of childbearing potential must use an adequate method of contraception and have a negative pregnancy test.

You may not qualify if:

• Use of antidiabetic agent other than insulin or insulin analog at the time of screening.
• Use of sodium-glucose cotransporter (SGLT) inhibitors within 8 weeks prior to screening.
• Chronic systemic corticosteroid use.
• Type 2 diabetes mellitus (T2DM), or severely uncontrolled T1D as determined by the Investigator.

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (96)

Lexicon Investigational Site

Linz, 4021, Austria

Location

Lexicon Investigational Site

Vienna, 1010, Austria

Location

Lexicon Investigational Site

Vienna, 1030, Austria

Location

Lexicon Investigational Site

Vienna, 1130, Austria

Location

Lexicon Investigational Site

Vienna, 1160, Austria

Location

Lexicon Investigational Site

Antwerp, 2018, Belgium

Location

Lexicon Investigational Site

Brussels, 1090, Belgium

Location

Lexicon Investigational Site

Edegem, 2650, Belgium

Location

Lexicon Investigational Site

Leuven, 3000, Belgium

Location

Lexicon Investigational Site

Sint-Niklaas, 9100, Belgium

Location

Lexicon Investigational Site

Lovech, 5500, Bulgaria

Location

Lexicon Investigational Site

Plovdiv, 4002, Bulgaria

Location

Lexicon Investigational Site

Rousse, 7002, Bulgaria

Location

Lexicon Investigational Site

Smolyan, 4700, Bulgaria

Location

Lexicon Investigational Site

Sofia, 1750, Bulgaria

Location

Lexicon Investigational Site

Varna, 9000, Bulgaria

Location

Lexicon Investigational Site

Béziers, 34500, France

Location

Lexicon Investigational Site

Dijon, 21079, France

Location

Lexicon Investigational Site

Nantes, 44000, France

Location

Lexicon Investigational Site

Nantes, 44093, France

Location

Lexicon Investigational Site

Nîmes, 30029, France

Location

Lexicon Investigational Site

Düsseldorf, 40210, Germany

Location

Lexicon Investigational Site

Hamburg, 21073, Germany

Location

Lexicon Investigational Site

Hamburg, 22607, Germany

Location

Lexicon Investigational Site

Hanover, 30173, Germany

Location

Lexicon Investigational Site

Mainz, 55116, Germany

Location

Lexicon Investigational Site

Münster, 48145, Germany

Location

Lexicon Investigational Site

Neuwied, 56564, Germany

Location

Lexicon Investigational Site

Budapest, 1027, Hungary

Location

Lexicon Investigational Site

Budapest, 1042, Hungary

Location

Lexicon Investigational Site

Budapest, 1097, Hungary

Location

Lexicon Investigational Site

Budapest, 1106, Hungary

Location

Lexicon Investigational Site

Budapest, 1134, Hungary

Location

Lexicon Investigational Site

Gyula, 5700, Hungary

Location

Lexicon Investigational Site

Hódmezővásárhely, 6800, Hungary

Location

Lexicon Investigational Site

Zalaegerszeg, 8900, Hungary

Location

Lexicon Investigational Site

Haifa, 31096, Israel

Location

Lexicon Investigational Site

Holon, 58100, Israel

Location

Lexicon Investigational Site

Jerusalem, 91120, Israel

Location

Lexicon Investigational Site

Petah Tikva, 49202, Israel

Location

Lexicon Investigational Site

Tel Aviv, 61480, Israel

Location

Lexicon Investigational Site

Tel Litwinsky, 52621, Israel

Location

Lexicon Investigational Site

Ẕerifin, 70300, Israel

Location

Lexicon Investigational Site

Catania, 95123, Italy

Location

Lexicon Investigational Site

Milan, 20132, Italy

Location

Lexicon Investigational Site

Palermo, 90127, Italy

Location

Lexicon Investigational Site

Perugia, 06126, Italy

Location

Lexicon Investigational Site

Pisa, 56124, Italy

Location

Lexicon Investigational Site

Roma, 00128, Italy

Location

Lexicon Investigational Site

Jonava, LT-55201, Lithuania

Location

Lexicon Investigational Site

Kaunas, LT-49449, Lithuania

Location

Lexicon Investigational Site

Kaunas, LT-50161, Lithuania

Location

Lexicon Investigational Site

Dordrecht, 3318, Netherlands

Location

Lexicon Investigational Site

Katowice, 40-060, Poland

Location

Lexicon Investigational Site

Krakow, 30-015, Poland

Location

Lexicon Investigational Site

Lodz, 90-242, Poland

Location

Lexicon Investigational Site

Lublin, 20-538, Poland

Location

Lexicon Investigational Site

Poznan, 61-655, Poland

Location

Lexicon Investigational Site

Szczecin, 70-506, Poland

Location

Lexicon Investigational Site

Warsaw, 01-518, Poland

Location

Lexicon Investigational Site

Warsaw, 02-507, Poland

Location

Lexicon Investigational Site

Warsaw, 04-736, Poland

Location

Lexicon Investigational Site

Bacau, 600238, Romania

Location

Lexicon Investigational Site

Bucharest, 010507, Romania

Location

Lexicon Investigational Site

Bucharest, 013764, Romania

Location

Lexicon Investigational Site

Buzău, 120203, Romania

Location

Lexicon Investigational Site

Galati, 800098, Romania

Location

Lexicon Investigational Site

Oradea, 410159, Romania

Location

Lexicon Investigational Site

Sibiu, 550371, Romania

Location

Lexicon Investigational Site

Târgu Mureş, 540142, Romania

Location

Lexicon Investigational Site

Bratislava, 821 02, Slovakia

Location

Lexicon Investigational Site

Bratislava, 851 01, Slovakia

Location

Lexicon Investigational Site

Košice, 040 01, Slovakia

Location

Lexicon Investigational Site

Nové Zámky, 940 01, Slovakia

Location

Lexicon Investigational Site

Štúrovo, 943 01, Slovakia

Location

Lexicon Investigational Site

Vrútky, 038 61, Slovakia

Location

Lexicon Investigational Site

Barcelona, 08035, Spain

Location

Lexicon Investigational Site

Barcelona, 08036, Spain

Location

Lexicon Investigational Site

Granada, 18012, Spain

Location

Lexicon Investigational Site

Málaga, 29006, Spain

Location

Lexicon Investigational Site

Seville, 41003, Spain

Location

Lexicon Investigational Site

Seville, 41009, Spain

Location

Lexicon Investigational Site

Seville, 41010, Spain

Location

Lexicon Investigational Site

Seville, 41014, Spain

Location

Lexicon Investigational Site

Valencia, 46014, Spain

Location

Lexicon Investigational Site

Härnösand, 871 82, Sweden

Location

Lexicon Investigational Site

Kristianstad, 291 85, Sweden

Location

Lexicon Investigational Site

Stockholm, 112 21, Sweden

Location

Lexicon Investigational Site

Sankt Gallen, 9007, Switzerland

Location

Lexicon Investigational Site

Birmingham, B15 2TH, United Kingdom

Location

Lexicon Investigational Site

Blackburn, BB2 3HH, United Kingdom

Location

Lexicon Investigational Site

Bristol, BS10 5NB, United Kingdom

Location

Lexicon Investigational Site

Glasgow, G4 0SF, United Kingdom

Location

Lexicon Investigational Site

Leeds, LS2 9JT, United Kingdom

Location

Lexicon Investigational Site

Leicester, LE5 4PW, United Kingdom

Location

Lexicon Investigational Site

Sheffield, S5 7AU, United Kingdom

Location

Related Publications (5)

• Peters AL, McGuire DK, Danne T, Kushner JA, Rodbard HW, Dhatariya K, Sawhney S, Banks P, Jiang W, Davies MJ, Lapuerta P. Diabetic Ketoacidosis and Related Events With Sotagliflozin Added to Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of the inTandem 1 and 2 Studies. Diabetes Care. 2020 Nov;43(11):2713-2720. doi: 10.2337/dc20-0924. Epub 2020 Sep 14.

  PMID: 32928957 DERIVED

• Danne T, Joish VN, Afonso M, Banks P, Sawhney S, Lapuerta P, Davies MJ, Buse JB, Lin D, Reaney M, Guillonneau S, Snoek FJ, Bailey TS, Polonsky WH. Improvement in Patient-Reported Outcomes in Adults with Type 1 Diabetes Treated with Sotagliflozin plus Insulin Versus Insulin Alone. Diabetes Technol Ther. 2021 Jan;23(1):70-77. doi: 10.1089/dia.2020.0068.

  PMID: 32721228 DERIVED

• Ervin C, Joish VN, Evans E, DiBenedetti D, Reaney M, Preblick R, Castro R, Danne T, Buse JB, Lapuerta P. Insights Into Patients' Experience With Type 1 Diabetes: Exit Interviews From Phase III Studies of Sotagliflozin. Clin Ther. 2019 Nov;41(11):2219-2230.e6. doi: 10.1016/j.clinthera.2019.09.003. Epub 2019 Oct 3.

  PMID: 31587812 DERIVED

• Danne T, Cariou B, Buse JB, Garg SK, Rosenstock J, Banks P, Kushner JA, McGuire DK, Peters AL, Sawhney S, Strumph P. Improved Time in Range and Glycemic Variability With Sotagliflozin in Combination With Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of 24-Week Continuous Glucose Monitoring Data From the inTandem Program. Diabetes Care. 2019 May;42(5):919-930. doi: 10.2337/dc18-2149. Epub 2019 Mar 4.

  PMID: 30833371 DERIVED

• Danne T, Cariou B, Banks P, Brandle M, Brath H, Franek E, Kushner JA, Lapuerta P, McGuire DK, Peters AL, Sawhney S, Strumph P. HbA1c and Hypoglycemia Reductions at 24 and 52 Weeks With Sotagliflozin in Combination With Insulin in Adults With Type 1 Diabetes: The European inTandem2 Study. Diabetes Care. 2018 Sep;41(9):1981-1990. doi: 10.2337/dc18-0342. Epub 2018 Jun 24.

  PMID: 29937431 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

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; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Sangeeta Sawhney, M.D.

  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: April 15, 2015
• First Posted: April 20, 2015
• Study Start: May 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: June 23, 2017
• Last Updated: February 12, 2020
• Results First Posted: October 30, 2019

Record last verified: 2020-02

Locations

FR (5); BE (5); PL (9); BU (6); LI (3); NL (1); ES (9); SE (3); RO (8); AU (5); GB (7); HU (8); CH (1); DE (7); SL (6); IL (7); IT (6)