Dose-ranging Study in Patients With Type 1 Diabetes Mellitus (inTandem4)

A Phase 2b, Dose-ranging, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study in Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy

The primary objective of this study was to define the dose leading to desirable efficacy, as measured by the change in hemoglobin A1C (A1C) between Baseline and Week 12.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Sotagliflozin

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Concord, California, United States, 94520
      • Lexicon Investigational Site
    • Ventura, California, United States, 93003
      • Lexicon Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80209
      • Lexicon Investigational Site
  • Florida
    • Jacksonville, Florida, United States, 32225
      • Lexicon Investigational Site
    • Miami, Florida, United States, 33175
      • Lexicon Investigational Site
  • Illinois
    • Springfield, Illinois, United States, 62711
      • Lexicon Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Lexicon Investigational Site
  • Maine
    • Auburn, Maine, United States, 04210
      • Lexicon Investigational Site
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Lexicon Investigational Site
  • Montana
    • Great Falls, Montana, United States, 59405
      • Lexicon Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Lexicon Investigational Site
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • Lexicon Investigational Site
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Lexicon Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • Lexicon Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Lexicon Investigational Site
  • Virginia
    • Chesapeake, Virginia, United States, 23321
      • Lexicon Investigational Site
    • Manassas, Virginia, United States, 20110
      • 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:

• Participant 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 type 1 diabetes mellitus (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 injection (MDI).
• At the Screening Visit, A1C had to be between 7.0% and 10.0%.
• Females of childbearing potential had to use an adequate method of contraception and have 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Drug: Placebo; Placebo, once daily, before the first meal of the day
Experimental: Sotagliflozin 75 mg; Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks.	Drug: Placebo; Placebo, once daily, before the first meal of the day; Drug: Sotagliflozin; Sotagliflozin,once daily, before the first meal of the day
Experimental: Sotagliflozin 200 mg; Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally for 12 weeks.	Drug: Placebo; Placebo, once daily, before the first meal of the day; Drug: Sotagliflozin; Sotagliflozin,once daily, before the first meal of the day
Experimental: Sotagliflozin 400 mg; Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally for 12 weeks.	Drug: Sotagliflozin; Sotagliflozin,once daily, before the first meal of the day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1C (A1C) at Week 12	Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-baseline Least Square (LS) mean values were obtained from mixed-effects model repeated measures (MMRM) model with treatment, randomization strata of insulin delivery method (continuous subcutaneous insulin infusion [CSII] or multiple daily injection [MDI]), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline A1C-by-time interaction as a covariate.	Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 12 in 2-Hour Postprandial Glucose (PPG) Following the Standardized Mixed Meal	A 2-hour PPG sample (plasma) was obtained 2-hours after a standardized Mixed Meal at Baseline (Day 1) and at the visit at Week 12. Post-Baseline LS mean was obtained from analysis of covariance (ANCOVA) model with treatment, randomization strata of insulin delivery method (CSII, MDI) as fixed categorical effects, and baseline postprandial glucose as a covariate.	Baseline, Week 12
Absolute Change From Baseline in Body Weight to Week 12	Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline weight-by-time interaction as a covariate.	Baseline to Week 12
Percent Change From Baseline in Body Weight to Week 12	Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline weight-by-time interaction as a covariate.	Baseline to Week 12
Change From Baseline to Week 12 in 24-Hour Urinary Glucose Excretion	Urine was collected over 24 hours to measure Urinary Glucose Excretion at baseline, and at the end of the 12-week treatment. Post-Baseline LS mean was obtained from ANCOVA model with treatment, randomization strata of insulin delivery method (CSII, MDI) as fixed categorical effects, and Baseline urinary glucose excretion as a covariate.	Baseline, Week 12
Change From Baseline to Week 12 in Fasting Plasma Glucose	Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline fasting plasma glucose-by-time interaction as a covariate.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Lexicon Pharmaceuticals
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Baker C, Wason S, Banks P, Sawhney S, Chang A, Danne T, Gesty-Palmer D, Kushner JA, McGuire DK, Mikell F, O'Neill M, Peters AL, Strumph P. Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: The inTandem4 trial. Diabetes Obes Metab. 2019 Nov;21(11):2440-2449. doi: 10.1111/dom.13825. Epub 2019 Aug 1.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: May 29, 2015
• First Submitted That Met QC Criteria: June 1, 2015
• First Posted (Estimate): June 2, 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: LX4211.1-206-T1DM; LX4211.206 (Other Identifier: Lexicon Pharmaceuticals, Inc.)