A Phase 3 Study to Evaluate the Safety of Sotagliflozin in Patients With Type 1 Diabetes Who Have Inadequate Glycemic Control With Insulin Therapy Alone (inTandem3)

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Net Clinical Benefit of Sotagliflozin as Adjunct to Insulin Therapy in Type 1 Diabetes

This Phase 3 study was designed to demonstrate the net benefit of sotagliflozin versus placebo in patients with Type 1 Diabetes (T1D).

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus (T1DM); High Level of Sugar (Glucose) in the Blood
• Intervention / Treatment: Drug: Placebo; Drug: Sotagliflozin

• Study Type: Interventional
• Enrollment (Actual): 1405
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, B7600FZN
    • Lexicon Investigational Site
  • Buenos Aires, Argentina, C1180AAX
    • Lexicon Investigational Site
  • Cordoba
    • Córdoba, Cordoba, Argentina, X5006IKK
      • Lexicon Investigational Site
• Australia
  • New South Wales
    • Coffs Harbour, New South Wales, Australia, 2450
      • Lexicon Investigational Site
    • Merewether, New South Wales, Australia, 2291
      • Lexicon Investigational Site
    • St Leonards, New South Wales, Australia, 2065
      • Lexicon Investigational Site
    • Wollongong, New South Wales, Australia, 2500
      • Lexicon Investigational Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Lexicon Investigational Site
  • South Australia
    • Keswick, South Australia, Australia, 5035
      • Lexicon Investigational Site
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Lexicon Investigational Site
    • Fitzroy, Victoria, Australia, 3065
      • Lexicon Investigational Site
    • Parkville, Victoria, Australia, 3050
      • Lexicon Investigational Site
• Belgium
  • Aalst, Belgium, 9300
    • Lexicon Investigational Site
  • Gent, Belgium, 9000
    • Lexicon Investigational Site
  • Sint-Niklaas, Belgium, 9100
    • Lexicon Investigational Site
• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Lexicon Investigational Site
  • Ruse, Bulgaria, 7003
    • Lexicon Investigational Site
  • Smolyan, Bulgaria, 4700
    • Lexicon Investigational Site
  • Sofia, Bulgaria, 1431
    • Lexicon Investigational Site
  • Sofia, Bulgaria, 1750
    • Lexicon Investigational Site
  • Varna, Bulgaria, 9000
    • Lexicon Investigational Site
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Y 3W2
      • Lexicon Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Lexicon Investigational Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • Lexicon Investigational Site
    • London, Ontario, Canada, N6A 4V2
      • Lexicon Investigational Site
    • Markham, Ontario, Canada, L6B 0P9
      • Lexicon Investigational Site
    • Oakville, Ontario, Canada, L6M 1M1
      • Lexicon Investigational Site
    • Thornhill, Ontario, Canada, L4J 8L7
      • Lexicon Investigational Site
    • Toronto, Ontario, Canada, M4G 3E8
      • Lexicon Investigational Site
  • Quebec
    • Sherbrooke, Quebec, Canada, J1G 5K2
      • Lexicon Investigational Site
    • St. Laurent, Quebec, Canada, H4T 1Z9
      • Lexicon Investigational Site
• Colombia
  • Atlantico, Colombia, 080020
    • Lexicon Investigational Site
  • Cundinamarca, Colombia, 110221
    • Lexicon Investigational Site
  • Cundinamarca, Colombia, 111211
    • Lexicon Investigational Site
  • Cundinamarca, Colombia, 111311
    • Lexicon Investigational Site
• Czechia
  • Krnov, Czechia, 794 01
    • Lexicon Investigational Site
  • Olomouc, Czechia, 779 00
    • Lexicon Investigational Site
  • Ostrava, Czechia, 702 00
    • Lexicon Investigational Site
  • Praha 10, Czechia, 104 00
    • Lexicon Investigational Site
  • Praha 4, Czechia, 149 00
    • Lexicon Investigational Site
  • Praha 5, Czechia, 150 98
    • Lexicon Investigational Site
• France
  • Corbeil-Essonnes, France, 91106
    • Lexicon Investigational Site
  • Pierre-Bénite, France, 69495
    • Lexicon Investigational Site
• Germany
  • Aschaffenburg, Germany, 63739
    • Lexicon Investigational Site
  • Asslar, Germany, 35614
    • Lexicon Investigational Site
  • Palatinate
    • Mainz, Palatinate, Germany, 55116
      • Lexicon Investigational Site
  • Rosenberg Bavaria
    • Sulzbach, Rosenberg Bavaria, Germany, 92237
      • Lexicon Investigational Site
  • Westphalia
    • Münster, Westphalia, Germany, 48153
      • Lexicon Investigational Site
• Hungary
  • Budapest, Hungary, 1027
    • Lexicon Investigational Site
  • Budapest, Hungary, 1033
    • Lexicon Investigational Site
  • Budapest, Hungary, 1088
    • Lexicon Investigational Site
  • Budapest, Hungary, 1213
    • Lexicon Investigational Site
  • Eger, Hungary, 3300
    • Lexicon Investigational Site
  • Esztergom, Hungary, 2500
    • Lexicon Investigational Site
  • Gyor, Hungary, 9023
    • Lexicon Investigational Site
  • Sátoraljaújhely, Hungary, 3980
    • Lexicon Investigational Site
• Israel
  • Holon, Israel, 58100
    • Lexicon Investigational Site
  • Petach-Tikvah, Israel, 4920235
    • Lexicon Investigational Site
  • Petah Tikva, Israel, 4941492
    • Lexicon Investigational Site
  • Rehovot, Israel, 76100
    • Lexicon Investigational Site
  • Tel Hashomer, Israel, 56261
    • Lexicon Investigational Site
• Italy
  • Bologna, Italy, 40138
    • Lexicon Investigational Site
  • Catania, Italy, 95122
    • Lexicon Investigational Site
  • Catania, Italy, 95123
    • Lexicon Investigational Site
  • Latina, Italy, 04100
    • Lexicon Investigational Site
  • Milan, Italy, 20132
    • Lexicon Investigational Site
  • Rome, Italy, 00128
    • Lexicon Investigational Site
• New Zealand
  • Christchurch, New Zealand, 8011
    • Lexicon Investigational Site
  • Otahuhu, New Zealand, 1640
    • Lexicon Investigational Site
  • Auckland
    • Epsom, Auckland, New Zealand, 1051
      • Lexicon Investigational Site
    • Takapuna, Auckland, New Zealand, 0620
      • Lexicon Investigational Site
  • Canterbury
    • Christchurch, Canterbury, New Zealand, 8001
      • Lexicon Investigational Site
  • Otago
    • Dunedin, Otago, New Zealand, 9016
      • Lexicon Investigational Site
  • Wellington
    • Newtown, Wellington, New Zealand, 6021
      • Lexicon Investigational Site
• Poland
  • Gdynia, Poland, 81-338
    • Lexicon Investigational Site
  • Katowice, Poland, 40-060
    • Lexicon Investigational Site
  • Katowice, Poland, 40-954
    • Lexicon Investigational Site
  • Lublin, Poland, 20-538
    • Lexicon Investigational Site
  • Warsaw, Poland, 01-868
    • Lexicon Investigational Site
  • Warsaw, Poland, 04-736
    • Lexicon Investigational Site
  • Warszawa, Poland, 02-507
    • Lexicon Investigational Site
• Slovakia
  • Bardejov, Slovakia, 085 01
    • Lexicon Investigational Site
  • Bratislava, Slovakia, 851 01
    • Lexicon Investigational Site
  • Bratislava, Slovakia, 85101
    • Lexicon Investigational Site
  • Levice, Slovakia, 934 01
    • Lexicon Investigational Site
• South Africa
  • Bloemfontein, South Africa, 9300
    • Lexicon Investigational Site
  • Cape Town, South Africa, 7130
    • Lexicon Investigational Site
  • Cape Town, South Africa, 7580
    • Lexicon Investigational Site
  • Johannesburg, South Africa, 2198
    • Lexicon Investigational Site
  • Port Elizabeth, South Africa, 6045
    • Lexicon Investigational Site
  • Cape Town
    • Goodwood, Cape Town, South Africa, 7460
      • Lexicon Investigational Site
  • Mpumalanga
    • Middelburg, Mpumalanga, South Africa, 1055
      • Lexicon Investigational Site
• Spain
  • Barcelona, Spain, 08035
    • Lexicon Investigational Site
  • Barcelona, Spain, 08036
    • Lexicon Investigational Site
  • Malaga, Spain, 29006
    • Lexicon Investigational Site
  • Sevilla, Spain, 41009
    • Lexicon Investigational Site
  • Sevilla, Spain, 41071
    • Lexicon Investigational Site
• United Kingdom
  • Blackburn, United Kingdom, BB2 3HH
    • Lexicon Investigational Site
  • Guildford, United Kingdom, GU2 7XX
    • Lexicon Investigational Site
  • Leicester, United Kingdom, LE5 4PW
    • Lexicon Investigational Site
  • Northampton, United Kingdom, NN1 5BD
    • Lexicon Investigational Site
  • Scotland
    • Dundee, Scotland, United Kingdom, DD1 9SY
      • Lexicon Investigational Site
• United States
  • California
    • Concord, California, United States, 94520
      • Lexicon Investigational Site
    • Escondido, California, United States, 92025
      • Lexicon Investigational Site
    • La Jolla, California, United States, 92037
      • Lexicon Investigational Site
    • San Marcos, California, United States, 94401
      • Lexicon Investigational Site
    • Ventura, California, United States, 93003
      • Lexicon Investigational Site
    • Walnut Creek, California, United States, 94598
      • Lexicon Investigational Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Lexicon Investigational Site
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Lexicon Investigational Site
  • Florida
    • Orlando, Florida, United States, 32804
      • Lexicon Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • Lexicon Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Lexicon Investigational Site
    • Macon, Georgia, United States, 31210
      • Lexicon Investigational Site
    • Roswell, Georgia, United States, 30076
      • Lexicon Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Lexicon Investigational Site
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Lexicon Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Lexicon Investigational Site
  • Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • Lexicon Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Lexicon Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Lexicon Investigational Site
  • New York
    • Albany, New York, United States, 12206
      • Lexicon Investigational Site
    • Bronx, New York, United States, 10467
      • Lexicon Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Lexicon Investigational Site
    • Chapel Hill, North Carolina, United States, 27517
      • Lexicon Investigational Site
    • Greenville, North Carolina, United States, 27834
      • Lexicon Investigational Site
    • Morehead City, North Carolina, United States, 28557
      • Lexicon Investigational Site
  • North Dakota
    • Grand Forks, North Dakota, United States, 58201
      • Lexicon Investigational Site
  • Oregon
    • Bend, Oregon, United States, 97701
      • Lexicon Investigational Site
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Lexicon Investigational Site
  • Texas
    • Austin, Texas, United States, 78731
      • Lexicon Investigational Site
    • San Antonio, Texas, United States, 78229
      • Lexicon Investigational Site
    • Shavano Park, Texas, United States, 78231
      • Lexicon Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Lexicon Investigational Site
  • Washington
    • Seattle, Washington, United States, 98105
      • Lexicon Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 T1DM made at least 1 year prior to informed consent
• Participants were being treated with insulin or insulin analog
• Willing and able to perform self-monitoring of blood glucose (SMBG) and complete the study diary as required per protocol
• At the Screening Visit, A1C was between 7.0% to 11.0%
• Females of childbearing potential used an adequate method of contraception and had a negative pregnancy test

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Two placebo-matching to sotagliflozin tablets daily, orally, before the first meal of the day for 24 weeks.	Drug: Placebo; Placebo, once daily, before the first meal of the day
Experimental: Sotagliflozin 400 mg; Sotagliflozin 400 milligram (mg) (two 200 mg tablets) once daily, orally, before the first meal of the day for 24 weeks.	Drug: Sotagliflozin; Sotagliflozin, once daily, before the first meal of the day; Other Names: LX4211

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With A1C <7.0% at Week 24 and No Episode of Severe Hypoglycemia and No Episode of Diabetic Ketoacidosis (DKA) After Randomization	The primary composite endpoint included blood samples for the assessment of Hemoglobin A1C to determine the participants with a value <7.0%. A central blinded adjudication process determined whether participants experienced either DKA or Severe Hypoglycemia.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in A1C	Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. Least Squares (LS) means were obtained from a mixed-effects model for repeated measures (MMRM) model including all available post baseline data. A negative change from Baseline (a lower AIC value at Week 24) indicates an improvement.	Baseline to Week 24
Absolute Change From Baseline in Body Weight	Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model. A negative change from Baseline indicates a loss in body weight from Baseline to Week 24.	Baseline to Week 24
Change From Baseline in Systolic Blood Pressure (SBP) in the Subset of Participants With Baseline SBP >=130 Millimeter of Mercury (mmHg)	An automatic sphygmomanometer was used with instructions on blood pressure measurements to allow for standardization. Week 16 was used because the protocol required Investigators to keep participant's hypertensive medications stable between Baseline and Week 16, unless a change was required for safety reasons. Baseline was defined as the last value collected prior to the first does of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A negative change indicates a decrease in SBP between Baseline and Week 16.	Baseline to Week 16
Percent Change From Baseline in Mean Daily Bolus Insulin Dose	The mean bolus insulin dose in international units/day (IU/day) for Week 24 was the average over the 3 to 5 days prior to the Week 24 visit. The Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post Baseline values. A negative percent change from Baseline indicated a reduction in the amount of bolus insulin used and a positive percent change from Baseline indicated an increase in the amount of bolus insulin used between Baseline and Week 24.	Baseline to Week 24

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Collaborators: Sanofi
• Investigators: Study Director: Sangeeta Sawhney, MD, Lexicon Pharmaceuticals, Inc.

Publications and helpful links

General Publications

• Garg SK, Henry RR, Banks P, Buse JB, Davies MJ, Fulcher GR, Pozzilli P, Gesty-Palmer D, Lapuerta P, Simo R, Danne T, McGuire DK, Kushner JA, Peters A, Strumph P. Effects of Sotagliflozin Added to Insulin in Patients with Type 1 Diabetes. N Engl J Med. 2017 Dec 14;377(24):2337-2348. doi: 10.1056/NEJMoa1708337. Epub 2017 Sep 13.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2015
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: August 20, 2015
• First Submitted That Met QC Criteria: August 20, 2015
• First Posted (Estimate): August 21, 2015

Study Record Updates

• Last Update Posted (Actual): February 12, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
• Other Study ID Numbers: LX4211.1-312-T1DM; LX4211.312 (Other Identifier: Lexicon Pharmaceuticals, Inc.)