Dose-ranging Study in Patients With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The primary objective of this study was to define the dose leading to desirable efficacy, as measured by the change in hemoglobin A1C (A1C) between Baseline and Week 12.

Official Title
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A Phase 2b, Dose-ranging, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study in Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: Placebo
* Drug: Sotagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant had given written informed consent to participate in the study in accordance with local regulations. Adult participants 18 years and older with a diagnosis of type 1 diabetes mellitus (T1D) made at least 1 year prior to informed consent. Participants were being treated with insulin or insulin analog delivered via continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI). At the Screening Visit, A1C had to be between 7.0% and 10.0%. Females of childbearing potential had to use an adequate method of contraception and have a negative pregnancy test. Exclusion Criteria: Use of antidiabetic agent other than insulin or insulin analog at the time of screening. Use of sodium-glucose cotransporter (SGLT) inhibitors within 8 weeks prior to screening. Chronic systemic corticosteroid use. Type 2 diabetes mellitus (T2DM), or severely uncontrolled T1D as determined by the Investigator.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks. | Drug: Placebo<br>* Placebo, once daily, before the first meal of the day<br>|
| Experimental: Sotagliflozin 75 mg<br>Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks. | Drug: Placebo<br>* Placebo, once daily, before the first meal of the day<br>Drug: Sotagliflozin<br>* Sotagliflozin,once daily, before the first meal of the day<br>|
| Experimental: Sotagliflozin 200 mg<br>Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally for 12 weeks. | Drug: Placebo<br>* Placebo, once daily, before the first meal of the day<br>Drug: Sotagliflozin<br>* Sotagliflozin,once daily, before the first meal of the day<br>|
| Experimental: Sotagliflozin 400 mg<br>Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally for 12 weeks. | Drug: Sotagliflozin<br>* Sotagliflozin,once daily, before the first meal of the day<br>|

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. Post-baseline Least Square (LS) mean values were obtained from mixed-effects model repeated measures (MMRM) model with treatment, randomization strata of insulin delivery method (continuous subcutaneous insulin infusion [CSII] or multiple daily injection [MDI]), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline A1C-by-time interaction as a covariate. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in 2-Hour Postprandial Glucose (PPG) Following the Standardized Mixed Meal | 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. Post-Baseline LS mean was obtained from analysis of covariance (ANCOVA) model with treatment, randomization strata of insulin delivery method (CSII, MDI) as fixed categorical effects, and baseline postprandial glucose as a covariate. | Baseline, Week 12 | 
| Absolute Change From Baseline in Body Weight to Week 12 | Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline weight-by-time interaction as a covariate. | Baseline to Week 12 | 
| Percent Change From Baseline in Body Weight to Week 12 | Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline weight-by-time interaction as a covariate. | Baseline to Week 12 | 
| Change From Baseline to Week 12 in 24-Hour Urinary Glucose Excretion | Urine was collected over 24 hours to measure Urinary Glucose Excretion at baseline, and at the end of the 12-week treatment. Post-Baseline LS mean was obtained from ANCOVA model with treatment, randomization strata of insulin delivery method (CSII, MDI) as fixed categorical effects, and Baseline urinary glucose excretion as a covariate. | Baseline, Week 12 | 
| Change From Baseline to Week 12 in Fasting Plasma Glucose | Baseline was defined as the last value collected prior to the first dose of double-blind study medication. Post-Baseline LS mean was obtained from MMRM model with treatment, randomization strata of insulin delivery method (CSII, MDI), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline fasting plasma glucose-by-time interaction as a covariate. | Baseline to Week 12 |