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

• ClinicalTrials.gov Identifier: NCT02383940
• Recruitment Status: Completed
• First Posted: March 10, 2015
• Results First Posted: October 30, 2019
• Last Update Posted: February 12, 2020
• Sponsor: Lexicon Pharmaceuticals
• Collaborators: Juvenile Diabetes Research Foundation; Sanofi
• Information provided by (Responsible Party): Lexicon Pharmaceuticals

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.

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 87 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 2015
• Actual Primary Completion Date: September 2016
• Actual Study Completion Date: September 2016

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 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 12 weeks.	Drug: Sotagliflozin; Sotagliflozin 400 mg, once daily before the first meal of the day; Other Name: LX4211

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Hemoglobin A1C (A1C) at Week 12 [ Time Frame: Baseline, 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 :

1. Change From Baseline in Total Daily Bolus Insulin Dose and Total Daily Basal Insulin Dose at Week 12 [ Time Frame: Baseline, 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.
2. Change From Baseline in 2-hour Postprandial Glucose (PPG) Following a Standardized Mixed Meal at Week 12 [ Time Frame: Baseline, 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.
3. 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 [ Time Frame: Baseline, 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.
4. Change From Baseline in Number of Hypoglycemic Events/Day (<=70 mg/dL) by Self-Monitored Blood Glucose (SMBG) at Week 12 [ Time Frame: Baseline, 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 30 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, California

Lexicon Investigational Site

Tustin, California, United States, 92780

United States, Colorado

Lexicon Investigational Site

Aurora, Colorado, United States, 80045

United States, Connecticut

Lexicon Investigational Site

New Haven, Connecticut, United States, 06519

United States, Florida

Lexicon Investigational Site

Tampa, Florida, United States, 33612

Lexicon Investigational Site

West Palm Beach, Florida, United States, 33401

United States, Georgia

Lexicon Investigational Site

Atlanta, Georgia, United States, 30318

Lexicon Investigational Site

Roswell, Georgia, United States, 30076

United States, Indiana

Lexicon Investigational Site

Indianapolis, Indiana, United States, 46202

United States, Louisiana

Lexicon Investigational Site

New Orleans, Louisiana, United States, 70121

United States, Maine

Lexicon Investigational Site

Auburn, Maine, United States, 04210

United States, Massachusetts

Lexicon Investigational Site

Boston, Massachusetts, United States, 02215

United States, New York

Lexicon Investigational Site

Buffalo, New York, United States, 14222

United States, North Carolina

Lexicon Investigational Site

Wilmington, North Carolina, United States, 28401

United States, Texas

Lexicon Investigational Site

Austin, Texas, United States, 78749

United States, Utah

Lexicon Investigational Site

Salt Lake City, Utah, United States, 84107

Sponsors and Collaborators

Lexicon Pharmaceuticals

Juvenile Diabetes Research Foundation

Sanofi

Investigators

• Study Director: Sangeeta Sawhney, M.D.; Lexicon Pharmaceuticals, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Lexicon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02383940
• Other Study ID Numbers: LX4211.1-204-T1DM; LX4211.204 ( Other Identifier: Lexicon Pharmaceuticals, Inc. )
• First Posted: March 10, 2015
• Results First Posted: October 30, 2019
• Last Update Posted: February 12, 2020
• Last Verified: February 2020

Additional relevant 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