Safety and Efficacy of Sotagliflozin (LX4211) in Patients With Inadequately Controlled Type 1 Diabetes Mellitus
Primary Purpose
Type 1 Diabetes Mellitus
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sotagliflozin
Placebo
Sotagliflozin
Sponsored by
About this trial
This is an interventional treatment trial for Type 1 Diabetes Mellitus
Eligibility 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.
Sites / Locations
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
- Lexicon Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Sotagliflozin 400 mg - Pioneer Group
Placebo - Expansion Group
Sotagliflozin 400 mg - Expansion Group
Arm Description
Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.
Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Outcomes
Primary Outcome Measures
Percent Change From Baseline in Total Daily Bolus Amount of Exogenous Insulin Required Calculated Over Days 3 to 27 (Treatment Outpatient Period)
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
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)
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.
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)
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.
Change From Baseline in Fasting Plasma Glucose (FPG) at 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.
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
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.
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
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.
Change From Day 1 in 3-hour Urinary Glucose Excretion Following a Mixed Meal Tolerance Test (MMTT) to Day 29: Expansion Groups
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.
Full Information
NCT ID
NCT01742208
First Posted
November 20, 2012
Last Updated
February 10, 2020
Sponsor
Lexicon Pharmaceuticals
Collaborators
Sanofi
1. Study Identification
Unique Protocol Identification Number
NCT01742208
Brief Title
Safety and Efficacy of Sotagliflozin (LX4211) in Patients With Inadequately Controlled Type 1 Diabetes Mellitus
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
February 2013 (Actual)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
January 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lexicon Pharmaceuticals
Collaborators
Sanofi
4. Oversight
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 1 Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sotagliflozin 400 mg - Pioneer Group
Arm Type
Experimental
Arm Description
Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.
Arm Title
Placebo - Expansion Group
Arm Type
Placebo Comparator
Arm Description
Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.
Arm Title
Sotagliflozin 400 mg - Expansion Group
Arm Type
Experimental
Arm Description
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Intervention Type
Drug
Intervention Name(s)
Sotagliflozin
Other Intervention Name(s)
LX4211
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants received placebo-matching sotagliflozin tablets once daily for 29 days.
Intervention Type
Drug
Intervention Name(s)
Sotagliflozin
Other Intervention Name(s)
LX4211
Intervention Description
Participants received sotagliflozin once daily for 29 days; pioneer participants completed dosing prior to dosing any other study participants.
Primary Outcome Measure Information:
Title
Percent Change From Baseline in Total Daily Bolus Amount of Exogenous Insulin Required Calculated Over Days 3 to 27 (Treatment Outpatient Period)
Description
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.
Time Frame
Baseline, Day 3 to Day 27
Secondary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Baseline, Day 3 to Day 27
Title
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)
Description
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.
Time Frame
Baseline, Day 3 to Day 27
Title
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29
Description
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.
Time Frame
Baseline, Day 29
Title
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
Description
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.
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
Title
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
Description
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.
Time Frame
Baseline, Day 3 to Day 27
Title
Change From Day 1 in 3-hour Urinary Glucose Excretion Following a Mixed Meal Tolerance Test (MMTT) to Day 29: Expansion Groups
Description
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.
Time Frame
From 15 minutes before start of mixed meal until 180 min post start of mixed meal, on Day 1 and Day 29
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Strumph, M.D.
Organizational Affiliation
Lexicon Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Lexicon Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Lexicon Investigational Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
Lexicon Investigational Site
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States
Facility Name
Lexicon Investigational Site
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68131
Country
United States
Facility Name
Lexicon Investigational Site
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Lexicon Investigational Site
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27713
Country
United States
Facility Name
Lexicon Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75230
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
26049551
Citation
Sands AT, Zambrowicz BP, Rosenstock J, Lapuerta P, Bode BW, Garg SK, Buse JB, Banks P, Heptulla R, Rendell M, Cefalu WT, Strumph P. Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes. Diabetes Care. 2015 Jul;38(7):1181-8. doi: 10.2337/dc14-2806. Epub 2015 Jun 6.
Results Reference
derived
Learn more about this trial
Safety and Efficacy of Sotagliflozin (LX4211) in Patients With Inadequately Controlled Type 1 Diabetes Mellitus
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