Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Sotagliflozin (LX4211) in Patients With Inadequately Controlled Type 1 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01742208
Recruitment Status : Completed
First Posted : December 5, 2012
Results First Posted : October 30, 2019
Last Update Posted : February 12, 2020
Sponsor:
Collaborator:
Sanofi
Information provided by (Responsible Party):
Lexicon Pharmaceuticals

Brief Summary:
This Phase 2 study was intended to assess the pharmacodynamics (PD), pharmacokinetics (PK), safety and efficacy of sotagliflozin following daily oral administration for 29 days in participants with type 1 diabetes mellitus (T1DM).

Condition or disease Intervention/treatment Phase
Type 1 Diabetes Mellitus Drug: Sotagliflozin Drug: Placebo Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of LX4211 in Patients With Inadequately Controlled Type 1 Diabetes Mellitus
Actual Study Start Date : February 2013
Actual Primary Completion Date : January 2014
Actual Study Completion Date : January 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetes Type 1

Arm Intervention/treatment
Experimental: Sotagliflozin 400 mg - Pioneer Group
Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.
Drug: Sotagliflozin
Participants received sotagliflozin once daily for 29 days. Pioneer Group participants were to have completed dosing prior to any study drug administration in Expansion Groups.
Other Name: LX4211

Placebo Comparator: Placebo - Expansion Group
Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.
Drug: Placebo
Participants received placebo-matching sotagliflozin tablets once daily for 29 days.

Experimental: Sotagliflozin 400 mg - Expansion Group
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Drug: Sotagliflozin
Participants received sotagliflozin once daily for 29 days; pioneer participants completed dosing prior to dosing any other study participants.
Other Name: LX4211




Primary Outcome Measures :
  1. Percent Change From Baseline in Total Daily Bolus Amount of Exogenous Insulin Required Calculated Over Days 3 to 27 (Treatment Outpatient Period) [ Time Frame: Baseline, Day 3 to Day 27 ]
    Baseline was calculated as the mean value from Day -6 to -2 for Expansion groups and from Day -6 to Day -3 for Pioneer Group. Percent mean change from baseline was calculated as 100*(sum [each daily value - baseline]/number of assessments)/baseline over Days 3 to 27. Least squares (LS) Means and confidence interval (CI) for the Expansion groups were based on an analysis of covariance (ANCOVA) model with covariates of baseline mean total bolus insulin, treatment group, factor used to stratify the randomization (screening A1C <= 8%, > 8%), and random effect of participant*treatment group. LS Means and CI for the Pioneer Group were based on the arithmetic treatment mean.


Secondary Outcome Measures :
  1. Percent Mean Change From Baseline in Daily Bolus Amount of Exogenous Insulin Required at Each Meal Calculated Over Days 3 to 27 (Treatment Outpatient Period) [ Time Frame: Baseline, Day 3 to Day 27 ]
    Baseline was calculated as the mean value from Day -6 to -2 for Expansion groups and from Day -6 to Day -3 for Pioneer Group. Percent mean change from baseline was calculated as 100*(sum [each daily value - baseline] / number of assessments)/baseline over Days 3 to 27. Percent change was calculated and is presented separately for each meal: i.e., breakfast, lunch and dinner. LS Means and CI for the Expansion groups were based on an ANCOVA model . LS Means and CI for the Pioneer Group were based on the arithmetic treatment mean.

  2. Percent Change From Baseline in Total Daily Amount of Exogenous Insulin (Total Daily Bolus + Total Daily Basal) Required Calculated Over Days 3 to 27 (Treatment Outpatient Period) [ Time Frame: Baseline, Day 3 to Day 27 ]
    Baseline was calculated as the mean value from Day -6 to -2 for Expansion groups and from Day -6 to Day -3 for Pioneer Group. Percent mean change from baseline was calculated as 100*(sum [each daily value - baseline]/ number of assessments)/baseline over Days 3 to 27. LS Means and CI for the Expansion groups were based on an ANCOVA model. LS Means and CI for the Pioneer Group were based on the arithmetic treatment mean.

  3. Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29 [ Time Frame: Baseline, Day 29 ]
    Baseline was defined as the last non-missing assessment prior to first dose of study drug. Change in FPG was calculated by subtracting baseline value from Day 29 value. LS Means and CI for the Expansion groups were based on a linear mixed repeated measures model.

  4. Change From Day 1 in 3-hour Plasma Glucose AUC (AUC0-3 h) Following a Mixed Meal Tolerance Test (MMTT) at Day 29: Expansion Groups [ Time Frame: Prior to start of mixed meal and 30, 60, 90, 120 and 180 min post start of mixed meal, on Day 1 and Day 29 ]
    A MMTT with frequent blood sample collection and with urine collection was performed on Day 1 and Day 29. Participants fasted (with the exception of water or non-caffeinated, calorie-free beverages) for at least 8 hours before the start of the MMTT and until the final blood sample was collected. Study drug was to be given within 15 minutes before liquid "Boost® Original" breakfast. The area under the plasma concentration-time curve (AUC) from time-zero to 3h postdose on Day 1 and Day 29 was calculated using the linear-up/log-down trapezoidal rule. Change was calculated by subtracting Day 1 value from Day 29 value. LS Means and CI were based on a linear mixed model.

  5. Change From Baseline in Percent Time Per Day Spent in Euglycemic Range (>=70 and <=180 mg/dL) Over Days 3 to 27 (Treatment Outpatient Period) Based on Continuous Glucose Monitoring [ Time Frame: Baseline, Day 3 to Day 27 ]
    Baseline was calculated as the mean value from Day -6 to -2 for Expansion groups and from Day -6 to Day -3 for Pioneer Group. Change in percent time per day spent in euglycemic range was calculated by subtracting baseline value from Day 29 value. LS Means and CI for the Expansion groups were based on a mixed model. LS mean and CI for the Pioneer Group were based on the arithmetic treatment mean.

  6. Change From Day 1 in 3-hour Urinary Glucose Excretion Following a Mixed Meal Tolerance Test (MMTT) to Day 29: Expansion Groups [ Time Frame: From 15 minutes before start of mixed meal until 180 min post start of mixed meal, on Day 1 and Day 29 ]
    A MMTT with frequent blood sample collection and with urine collection was performed on Day 1 and Day 29. Participants fasted (with the exception of water or non-caffeinated, calorie-free beverages) for at least 8 hours before the start of the MMTT and until the final blood sample was collected. Study drug was to be given within 15 minutes before liquid "Boost® Original" breakfast. Participants were asked to void immediately before blood sample 15 minutes before start of mixed meal and immediately after the 180-minute (3 hour) blood sample was collected, and all urine between the -15 minute and post-180-minute time points was collected for urine glucose calculation. Change was calculated by subtracting Day 1 value from Day 29 value. LS Means were based on a linear mixed model.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults >=18 to <=55 years of age
  • Confirmed diagnosis of T1DM, diagnosed prior to age 40 years, and for at least 6 months prior to Screening
  • Willing to refrain from using carbohydrate counting to adjust insulin during the study
  • Willing and able to wear and operate a continuous glucose monitor
  • Willing and able to self-assess blood glucose
  • Willing and able to provide written informed consent.

Exclusion Criteria:

  • History of type 2 diabetes mellitus or diabetes resulting from acromegaly, Cushing's disease, chronic pancreatitis, or pancreatectomy
  • Two or more severe episodes of hypoglycemia that required emergency treatment within 3 months prior to Screening
  • Use of premixed insulin
  • History of diabetic ketoacidosis within 1 year of screening
  • Presence of active hepatic disease or clinically significant abnormal liver function tests
  • History of chronic pancreatitis
  • Participants with a history of heart attack, severe/unstable angina, or coronary revascularization procedure
  • History of clinically significant cardiac arrhythmias within 1 year prior to screening
  • Participants with congestive heart failure
  • Participants with uncontrolled Stage III hypertension
  • History of human immunodeficiency virus (HIV) or hepatitis C
  • History of illicit drug or alcohol abuse within 12 months prior to Screening
  • Use of any investigational agent or device within 30 days prior to Screening or any therapeutic protein or antibody within 90 days prior to Screening
  • Use of medication or herbal supplements taken for weight loss within 2 weeks of screening
  • Chronic use of any antidiabetic therapy other than insulin within 2 months prior to Screening
  • Use of systemic or inhaled corticosteroids within 2 weeks prior to Screening
  • Participants who underwent major surgery within 6 months prior to Screening
  • Inability or difficulty swallowing whole tablets or capsules
  • Women who were pregnant or breastfeeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01742208


Locations
Layout table for location information
United States, Colorado
Lexicon Investigational Site
Aurora, Colorado, United States, 80045
United States, Georgia
Lexicon Investigational Site
Atlanta, Georgia, United States, 30318
United States, Louisiana
Lexicon Investigational Site
Baton Rouge, Louisiana, United States, 70808
United States, Nebraska
Lexicon Investigational Site
Omaha, Nebraska, United States, 68131
United States, New York
Lexicon Investigational Site
Bronx, New York, United States, 10467
United States, North Carolina
Lexicon Investigational Site
Durham, North Carolina, United States, 27713
United States, Texas
Lexicon Investigational Site
Dallas, Texas, United States, 75230
Sponsors and Collaborators
Lexicon Pharmaceuticals
Sanofi
Investigators
Layout table for investigator information
Study Director: Paul Strumph, M.D. Lexicon Pharmaceuticals, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Lexicon Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01742208    
Other Study ID Numbers: LX4211.1-203-T1DM
LX4211.203 ( Other Identifier: Lexicon Pharmaceuticals, Inc. )
First Posted: December 5, 2012    Key Record Dates
Results First Posted: October 30, 2019
Last Update Posted: February 12, 2020
Last Verified: February 2020
Additional relevant MeSH terms:
Layout table for MeSH terms
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs