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

NCT02384941 | Completed Phase 3 Results DMC

• 1 other identifier: LX4211.1-309-T1DM
• Study Type: interventional
• Target: 793
• Locations: 2 countries
• Sites: 75

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

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 lower 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) Upto Week 24

  Baseline to Week 24

• Absolute 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 Total Treatment Satisfaction Scores as Measured by Total Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Scores at Week 24

  Baseline to Week 24

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Two placebo-matching sotagliflozin tables, orally for 24 weeks followed by a 28 week extension period.

Drug: Placebo

Sotagliflozin 200 milligrams (mg)

EXPERIMENTAL

Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), orally, for 24 weeks followed by a 28 week extension period.

Drug: Placebo; Drug: Sotagliflozin

Sotagliflozin 400 mg

EXPERIMENTAL

Sotagliflozin 400 mg (two 200 mg tablets), orally, for 24 weeks followed by a 28 week extension period.

Drug: Sotagliflozin

Interventions

Placebo DRUG

Placebo once daily, before first meal of the day.

Placebo; Sotagliflozin 200 milligrams (mg)

Sotagliflozin DRUG

Sotagliflozin once daily, before first meal of the day.

Also known as: LX4211

Sotagliflozin 200 milligrams (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 had given 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 were being treated with insulin or insulin analog delivered. via continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).
• Willing and able to perform self-monitored blood glucose (SMBG) and complete the study diary as required per protocol.
• At the Screening Visit, A1C must be 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 randomization.
• Chronic systemic corticosteroid use.
• Type 2 diabetes mellitus (T2D), or severely uncontrolled T1D as determined by the Investigator.

Sponsors & Collaborators

• Lexicon Pharmaceuticals: lead
• Sanofi: collaborator

Study Sites (75)

Lexicon Investigational Site

Birmingham, Alabama, 35294, United States

Location

Lexicon Investigational Site

Little Rock, Arkansas, 72205, United States

Location

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Escondido, California, 92025, United States

Location

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Greenbrae, California, 94904, United States

Location

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Huntington Beach, California, 92648, United States

Location

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La Jolla, California, 92037, United States

Location

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Los Angeles, California, 90057-3550, United States

Location

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Orange, California, 92868, United States

Location

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Palm Springs, California, 92262, United States

Location

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San Mateo, California, 94401, United States

Location

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Tarzana, California, 91356, United States

Location

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Tustin, California, 92780, United States

Location

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Walnut Creek, California, 94598, United States

Location

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Aurora, Colorado, 70045, United States

Location

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Longmont, Colorado, 80501, United States

Location

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Fleming Island, Florida, 32003, United States

Location

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Jacksonville, Florida, 32204, United States

Location

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Jacksonville, Florida, 32216, United States

Location

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New Port Richey, Florida, 34652, United States

Location

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Ormond Beach, Florida, 32174, United States

Location

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West Palm Beach, Florida, 33401, United States

Location

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Atlanta, Georgia, 30318, United States

Location

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Lawrenceville, Georgia, 30046, United States

Location

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Roswell, Georgia, 30076, United States

Location

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Honolulu, Hawaii, 96814, United States

Location

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Crystal Lake, Illinois, 60012, United States

Location

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Elgin, Illinois, 60123, United States

Location

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Springfield, Illinois, 62711, United States

Location

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Topeka, Kansas, 66606, United States

Location

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Lexington, Kentucky, 40503, United States

Location

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Bangor, Maine, 04401, United States

Location

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Baltimore, Maryland, 21204, United States

Location

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Boston, Massachusetts, 02215, United States

Location

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Detroit, Michigan, 46214, United States

Location

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Chesterfield, Missouri, 63017, United States

Location

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St Louis, Missouri, 63110, United States

Location

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Omaha, Nebraska, 68131, United States

Location

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Henderson, Nevada, 89052, United States

Location

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Las Vegas, Nevada, 89148, United States

Location

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Albany, New York, 12206, United States

Location

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New York, New York, 10029, United States

Location

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Asheville, North Carolina, 28803, United States

Location

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Chapel Hill, North Carolina, 27517, United States

Location

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Morehead City, North Carolina, 28557, United States

Location

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Columbus, Ohio, 43201, United States

Location

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Oklahoma City, Oklahoma, 73112, United States

Location

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Portland, Oregon, 97239, United States

Location

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Greer, South Carolina, 29651, United States

Location

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Rapid City, South Dakota, 57701, United States

Location

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Chattanooga, Tennessee, 37404, United States

Location

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Chattanooga, Tennessee, 37411, United States

Location

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Memphis, Tennessee, 38119, United States

Location

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Austin, Texas, 78749, United States

Location

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Dallas, Texas, 75230, United States

Location

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Dallas, Texas, 75231, United States

Location

Lexicon Investigational Site

Dallas, Texas, 75246, United States

Location

Lexicon Investigational Site

Houston, Texas, 77079, United States

Location

Lexicon Investigational Site

Houston, Texas, 77095, United States

Location

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San Antonio, Texas, 78258, United States

Location

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Schertz, Texas, 78154, United States

Location

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Chesapeake, Virginia, 23321, United States

Location

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Renton, Washington, 98057, United States

Location

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Seattle, Washington, 98105, United States

Location

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Calgary, Alberta, T2H 2G4, Canada

Location

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Vancouver, British Columbia, V5Z 1M9, Canada

Location

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Winnipeg, Manitoba, R3C 0N2, Canada

Location

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Halifax, Nova Scotia, B3H 1V7, Canada

Location

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Barrie, Ontario, L4M 7G1, Canada

Location

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Hamilton, Ontario, L8N 3Z5, Canada

Location

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London, Ontario, N6A 4V2, Canada

Location

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Ottawa, Ontario, K1H 7W9, Canada

Location

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Thornhill, Ontario, L4J 8L7, Canada

Location

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Toronto, Ontario, M4G 3E8, Canada

Location

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Montreal, Quebec, H2W 1R7, Canada

Location

Lexicon Investigational Site

Saint-Laurent, Quebec, H4T 1Z9, Canada

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

• Buse JB, Garg SK, Rosenstock J, Bailey TS, Banks P, Bode BW, Danne T, Kushner JA, Lane WS, Lapuerta P, McGuire DK, Peters AL, Reed J, Sawhney S, Strumph P. Sotagliflozin in Combination With Optimized Insulin Therapy in Adults With Type 1 Diabetes: The North American inTandem1 Study. Diabetes Care. 2018 Sep;41(9):1970-1980. doi: 10.2337/dc18-0343. Epub 2018 Jun 24.

  PMID: 29937430 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

800-633-1610

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: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: March 10, 2015
• Study Start: March 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: February 1, 2017
• Last Updated: February 12, 2020
• Results First Posted: November 25, 2019

Record last verified: 2020-02

Locations

CA (12); US (63)