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Efficacy and Safety of Sotagliflozin in Young Adult Patients With Type 1 Diabetes Mellitus and Elevated Hemoglobin A1C

Primary Purpose

Type 1 Diabetes Mellitus

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Sotagliflozin
Placebo
Sponsored by
Lexicon Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 1 Diabetes Mellitus

Eligibility Criteria

18 Years - 30 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Participant had given written informed consent.
  • Young adult participants >=18 to <=30 years old at Screening, with a confirmed diagnosis of T1DM made at least 1 year prior to informed consent.
  • Participants were being treated with insulin or insulin analogue delivered via continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).
  • At Screening, must had A1C >= 9.0%.
  • Must be willing and able to perform self-monitored blood glucose (SMBG) and complete the study diary.
  • Females of childbearing potential must use an adequate method of contraception and had a negative pregnancy test.

Exclusion Criteria:

  • Any prior use of LX4211/sotagliflozin.
  • Use of antidiabetic agent other than insulin or insulin analogue at the time of screening.
  • Use of sodium-glucose cotransporter (SGLT) inhibitors within 8 weeks prior to start of the placebo Run-in Period.
  • Chronic systemic corticosteroid use.
  • Type 2 diabetes, or severely uncontrolled diabetes mellitus as determined by the Investigator.
  • History of diabetic ketoacidosis (DKA) or nonketotic hyperosmolar state within 6 months prior to the Screening Visit.
  • History of severe hypoglycemic event within 1 month prior to the Screening Visit.

Sites / Locations

  • Lexicon Investigational Site
  • Lexicon Investigational Site
  • Lexicon Investigational Site
  • Lexicon Investigational Site
  • Lexicon Investigational Site
  • Lexicon Investigational Site
  • Lexicon Investigational Site
  • Lexicon Investigational Site
  • 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 Type

Placebo Comparator

Experimental

Arm Label

Placebo

Sotagliflozin 400 mg

Arm Description

Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.

Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.

Outcomes

Primary Outcome Measures

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. Change was calculated by subtracting baseline value from Week 12 value. Least Square (LS) mean changes from baseline were obtained from mixed model repeated measures (MMRM) model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week-4 A1C (<=10%, >10%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline A1C-by-time interaction as a covariate.

Secondary Outcome Measures

Change From Baseline in Total Daily Bolus Insulin Dose and Total Daily Basal Insulin Dose at Week 12
The daily bolus and basal insulin doses were calculated as an average of the doses over 3 to 5 days before each visit (Baseline and Week 12). Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from MMRM model.
Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Standardized Mixed Meal at Week 12
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. At Week 12, study drug was to be given within 15 minutes before liquid "Boost®," "Ensure®," or similar nutrition drink product; at baseline, study drug was to be given after the 2-hour post-Mixed Meal PPG sample. Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from analysis of covariance (ANCOVA) model.
Change From Baseline in Glycemic Instability by Hyperglycemia (Continuous Glucose Monitoring [CGM] Area Under the Curve [AUC] >150 mg/dL) and Hypoglycemia (CGM AUC <70 mg/dL) Over a 24-hour Period at Week 12
Glycemic instability (mg/dL*minutes/1000) by hyperglycemia/hypoglycemia was measured by CGM AUC outside target range (as a daily average over the week prior to the visit [Baseline and Week 12]) over 24 hours, where outside target range was defined as CGM glucose AUC >150 mg/dL (hyperglycemia) and CGM glucose AUC <70 mg/dL (hypoglycemia). Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from MMRM model.
Change From Baseline in Number of Hypoglycemic Events/Day (<=70 mg/dL) by Self-Monitored Blood Glucose (SMBG) at Week 12
Hypoglycemic event by SMBG was defined as an event in which the fingerstick measurement was <=70 mg/dL. The number of hypoglycemic events per day was calculated as a daily average number of episodes over the week prior to visit (Baseline and Week 12). Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from MMRM model.

Full Information

First Posted
February 19, 2015
Last Updated
February 10, 2020
Sponsor
Lexicon Pharmaceuticals
Collaborators
Juvenile Diabetes Research Foundation, Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT02383940
Brief Title
Efficacy and Safety of Sotagliflozin in Young Adult Patients With Type 1 Diabetes Mellitus and Elevated Hemoglobin A1C
Official Title
A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of LX4211 in Young Adult Patients With Type 1 Diabetes Mellitus and Elevated Hemoglobin A1C
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
April 2015 (Actual)
Primary Completion Date
September 2016 (Actual)
Study Completion Date
September 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lexicon Pharmaceuticals
Collaborators
Juvenile Diabetes Research Foundation, Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This Phase 2 study was intended to demonstrate superiority of sotagliflozin versus placebo on Hemoglobin A1C (A1C) reduction at Week 12 in young adult participants with type 1 diabetes mellitus (T1DM) who have poor glycemic control on their current insulin regimen.

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 ProviderInvestigator
Allocation
Randomized
Enrollment
87 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks.
Arm Title
Sotagliflozin 400 mg
Arm Type
Experimental
Arm Description
Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Sotagliflozin
Other Intervention Name(s)
LX4211
Intervention Description
Sotagliflozin 400 mg, once daily before the first meal of the day
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo, once daily before the first meal of the day
Primary Outcome Measure Information:
Title
Change From Baseline in Hemoglobin A1C (A1C) at Week 12
Description
Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Change was calculated by subtracting baseline value from Week 12 value. Least Square (LS) mean changes from baseline were obtained from mixed model repeated measures (MMRM) model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week-4 A1C (<=10%, >10%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline A1C-by-time interaction as a covariate.
Time Frame
Baseline, Week 12
Secondary Outcome Measure Information:
Title
Change From Baseline in Total Daily Bolus Insulin Dose and Total Daily Basal Insulin Dose at Week 12
Description
The daily bolus and basal insulin doses were calculated as an average of the doses over 3 to 5 days before each visit (Baseline and Week 12). Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from MMRM model.
Time Frame
Baseline, Week 12
Title
Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Standardized Mixed Meal at Week 12
Description
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. At Week 12, study drug was to be given within 15 minutes before liquid "Boost®," "Ensure®," or similar nutrition drink product; at baseline, study drug was to be given after the 2-hour post-Mixed Meal PPG sample. Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from analysis of covariance (ANCOVA) model.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Glycemic Instability by Hyperglycemia (Continuous Glucose Monitoring [CGM] Area Under the Curve [AUC] >150 mg/dL) and Hypoglycemia (CGM AUC <70 mg/dL) Over a 24-hour Period at Week 12
Description
Glycemic instability (mg/dL*minutes/1000) by hyperglycemia/hypoglycemia was measured by CGM AUC outside target range (as a daily average over the week prior to the visit [Baseline and Week 12]) over 24 hours, where outside target range was defined as CGM glucose AUC >150 mg/dL (hyperglycemia) and CGM glucose AUC <70 mg/dL (hypoglycemia). Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from MMRM model.
Time Frame
Baseline, Week 12
Title
Change From Baseline in Number of Hypoglycemic Events/Day (<=70 mg/dL) by Self-Monitored Blood Glucose (SMBG) at Week 12
Description
Hypoglycemic event by SMBG was defined as an event in which the fingerstick measurement was <=70 mg/dL. The number of hypoglycemic events per day was calculated as a daily average number of episodes over the week prior to visit (Baseline and Week 12). Change was calculated by subtracting baseline value from Week 12 value. LS mean changes from baseline were obtained from MMRM model.
Time Frame
Baseline, Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant had given written informed consent. Young adult participants >=18 to <=30 years old at Screening, with a confirmed diagnosis of T1DM made at least 1 year prior to informed consent. Participants were being treated with insulin or insulin analogue delivered via continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). At Screening, must had A1C >= 9.0%. Must be willing and able to perform self-monitored blood glucose (SMBG) and complete the study diary. Females of childbearing potential must use an adequate method of contraception and had a negative pregnancy test. Exclusion Criteria: Any prior use of LX4211/sotagliflozin. Use of antidiabetic agent other than insulin or insulin analogue at the time of screening. Use of sodium-glucose cotransporter (SGLT) inhibitors within 8 weeks prior to start of the placebo Run-in Period. Chronic systemic corticosteroid use. Type 2 diabetes, or severely uncontrolled diabetes mellitus as determined by the Investigator. History of diabetic ketoacidosis (DKA) or nonketotic hyperosmolar state within 6 months prior to the Screening Visit. History of severe hypoglycemic event within 1 month prior to the Screening Visit.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sangeeta Sawhney, M.D.
Organizational Affiliation
Lexicon Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Lexicon Investigational Site
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
Lexicon Investigational Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Lexicon Investigational Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06519
Country
United States
Facility Name
Lexicon Investigational Site
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Lexicon Investigational Site
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33401
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
Roswell
State/Province
Georgia
ZIP/Postal Code
30076
Country
United States
Facility Name
Lexicon Investigational Site
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Lexicon Investigational Site
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Lexicon Investigational Site
City
Auburn
State/Province
Maine
ZIP/Postal Code
04210
Country
United States
Facility Name
Lexicon Investigational Site
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Lexicon Investigational Site
City
Buffalo
State/Province
New York
ZIP/Postal Code
14222
Country
United States
Facility Name
Lexicon Investigational Site
City
Wilmington
State/Province
North Carolina
ZIP/Postal Code
28401
Country
United States
Facility Name
Lexicon Investigational Site
City
Austin
State/Province
Texas
ZIP/Postal Code
78749
Country
United States
Facility Name
Lexicon Investigational Site
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84107
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32640846
Citation
Bode BW, Cengiz E, Wadwa RP, Banks P, Danne T, Kushner JA, McGuire DK, Peters AL, Strumph P, Sawhney S. Effects of Sotagliflozin Combined with Intensive Insulin Therapy in Young Adults with Poorly Controlled Type 1 Diabetes: The JDRF Sotagliflozin Study. Diabetes Technol Ther. 2021 Jan;23(1):59-69. doi: 10.1089/dia.2020.0079.
Results Reference
derived

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Efficacy and Safety of Sotagliflozin in Young Adult Patients With Type 1 Diabetes Mellitus and Elevated Hemoglobin A1C

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