Dose-ranging Study in Patients With Type 1 Diabetes Mellitus

Phase 2

Completed

Conditions: Type 1 Diabetes Mellitus

Interventions: Drug: Placebo
Drug: Sotagliflozin

Registration Number: NCT02459899

Lead Sponsor: Lexicon Pharmaceuticals

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 141

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sotagliflozin 200 mg	Placebo	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally for 12 weeks.
Sotagliflozin 200 mg	Sotagliflozin	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally for 12 weeks.
Sotagliflozin 400 mg	Sotagliflozin	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally for 12 weeks.
Placebo	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.
Sotagliflozin 75 mg	Placebo	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks.
Sotagliflozin 75 mg	Sotagliflozin	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Hemoglobin A1C (A1C) at Week 12	Baseline to 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.

Secondary Outcome Measures

Name	Time	Method
Absolute Change From Baseline in Body Weight to Week 12	Baseline 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.
Percent Change From Baseline in Body Weight to Week 12	Baseline 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.
Change From Baseline to Week 12 in Fasting Plasma Glucose	Baseline 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 fasting plasma glucose-by-time interaction as a covariate.
Change From Baseline to Week 12 in 2-Hour Postprandial Glucose (PPG) Following the Standardized Mixed Meal	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. 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.
Change From Baseline to Week 12 in 24-Hour Urinary Glucose Excretion	Baseline, Week 12	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.