A Phase 2, Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of LX4211 in Patients With Inadequately Controlled Type 1 Diabetes Mellitus
Overview
- Phase
- Phase 2
- Intervention
- Sotagliflozin
- Conditions
- Type 1 Diabetes Mellitus
- Sponsor
- Lexicon Pharmaceuticals
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Percent Change From Baseline in Total Daily Bolus Amount of Exogenous Insulin Required Calculated Over Days 3 to 27 (Treatment Outpatient Period)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
This Phase 2 study was intended to assess the pharmacodynamics (PD), pharmacokinetics (PK), safety and efficacy of sotagliflozin following daily oral administration for 29 days in participants with type 1 diabetes mellitus (T1DM).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Adults \>=18 to \<=55 years of age
- •Confirmed diagnosis of T1DM, diagnosed prior to age 40 years, and for at least 6 months prior to Screening
- •Willing to refrain from using carbohydrate counting to adjust insulin during the study
- •Willing and able to wear and operate a continuous glucose monitor
- •Willing and able to self-assess blood glucose
- •Willing and able to provide written informed consent.
Exclusion Criteria
- •History of type 2 diabetes mellitus or diabetes resulting from acromegaly, Cushing's disease, chronic pancreatitis, or pancreatectomy
- •Two or more severe episodes of hypoglycemia that required emergency treatment within 3 months prior to Screening
- •Use of premixed insulin
- •History of diabetic ketoacidosis within 1 year of screening
- •Presence of active hepatic disease or clinically significant abnormal liver function tests
- •History of chronic pancreatitis
- •Participants with a history of heart attack, severe/unstable angina, or coronary revascularization procedure
- •History of clinically significant cardiac arrhythmias within 1 year prior to screening
- •Participants with congestive heart failure
- •Participants with uncontrolled Stage III hypertension
Arms & Interventions
Sotagliflozin 400 mg - Pioneer Group
Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.
Intervention: Sotagliflozin
Placebo - Expansion Group
Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.
Intervention: Placebo
Sotagliflozin 400 mg - Expansion Group
Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Intervention: Sotagliflozin
Outcomes
Primary Outcomes
Percent Change From Baseline in Total Daily Bolus Amount of Exogenous Insulin Required Calculated Over Days 3 to 27 (Treatment Outpatient Period)
Time Frame: Baseline, Day 3 to Day 27
Baseline was calculated as the mean value from Day -6 to -2 for Expansion groups and from Day -6 to Day -3 for Pioneer Group. Percent mean change from baseline was calculated as 100\*(sum \[each daily value - baseline\]/number of assessments)/baseline over Days 3 to 27. Least squares (LS) Means and confidence interval (CI) for the Expansion groups were based on an analysis of covariance (ANCOVA) model with covariates of baseline mean total bolus insulin, treatment group, factor used to stratify the randomization (screening A1C \<= 8%, \> 8%), and random effect of participant\*treatment group. LS Means and CI for the Pioneer Group were based on the arithmetic treatment mean.
Secondary Outcomes
- Percent Mean Change From Baseline in Daily Bolus Amount of Exogenous Insulin Required at Each Meal Calculated Over Days 3 to 27 (Treatment Outpatient Period)(Baseline, Day 3 to Day 27)
- Change From Day 1 in 3-hour Plasma Glucose AUC (AUC0-3 h) Following a Mixed Meal Tolerance Test (MMTT) at Day 29: Expansion Groups(Prior to start of mixed meal and 30, 60, 90, 120 and 180 min post start of mixed meal, on Day 1 and Day 29)
- Change From Baseline in Percent Time Per Day Spent in Euglycemic Range (>=70 and <=180 mg/dL) Over Days 3 to 27 (Treatment Outpatient Period) Based on Continuous Glucose Monitoring(Baseline, Day 3 to Day 27)
- Percent Change From Baseline in Total Daily Amount of Exogenous Insulin (Total Daily Bolus + Total Daily Basal) Required Calculated Over Days 3 to 27 (Treatment Outpatient Period)(Baseline, Day 3 to Day 27)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29(Baseline, Day 29)
- Change From Day 1 in 3-hour Urinary Glucose Excretion Following a Mixed Meal Tolerance Test (MMTT) to Day 29: Expansion Groups(From 15 minutes before start of mixed meal until 180 min post start of mixed meal, on Day 1 and Day 29)