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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sotagliflozin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 12 weeks. | Drug: Placebo<br>* Placebo, once daily before the first meal of the day<br>|
| Experimental: Sotagliflozin 400 mg<br>Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before the first meal of the day for 12 weeks. | Drug: Sotagliflozin<br>* Sotagliflozin 400 mg, once daily before the first meal of the day<br>* Other names: LX4211;|

What is the study measuring?
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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. 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. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 12 | 
| 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. | Baseline, Week 12 | 
| 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. | Baseline, Week 12 | 
| 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. | Baseline, Week 12 |