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).
Brief Title
Safety and Efficacy of Sotagliflozin (LX4211) in Patients With Inadequately Controlled Type 1 Diabetes Mellitus
Categories
Completion Date
Completion Date Type
Actual
Conditions
Type 1 Diabetes Mellitus
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
* History of human immunodeficiency virus (HIV) or hepatitis C
* History of illicit drug or alcohol abuse within 12 months prior to Screening
* Use of any investigational agent or device within 30 days prior to Screening or any therapeutic protein or antibody within 90 days prior to Screening
* Use of medication or herbal supplements taken for weight loss within 2 weeks of screening
* Chronic use of any antidiabetic therapy other than insulin within 2 months prior to Screening
* Use of systemic or inhaled corticosteroids within 2 weeks prior to Screening
* Participants who underwent major surgery within 6 months prior to Screening
* Inability or difficulty swallowing whole tablets or capsules
* Women who were pregnant or breastfeeding.
* 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
* History of human immunodeficiency virus (HIV) or hepatitis C
* History of illicit drug or alcohol abuse within 12 months prior to Screening
* Use of any investigational agent or device within 30 days prior to Screening or any therapeutic protein or antibody within 90 days prior to Screening
* Use of medication or herbal supplements taken for weight loss within 2 weeks of screening
* Chronic use of any antidiabetic therapy other than insulin within 2 months prior to Screening
* Use of systemic or inhaled corticosteroids within 2 weeks prior to Screening
* Participants who underwent major surgery within 6 months prior to Screening
* Inability or difficulty swallowing whole tablets or capsules
* Women who were pregnant or breastfeeding.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
55 Years
Minimum Age
18 Years
NCT Id
NCT01742208
Org Class
Industry
Org Full Name
Lexicon Pharmaceuticals
Org Study Id
LX4211.1-203-T1DM
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Percent Change From Baseline in Total Daily Bolus Amount of Exogenous Insulin Required Calculated Over Days 3 to 27 (Treatment Outpatient Period)
Outcome Time Frame
Baseline, Day 3 to Day 27
Secondary Ids
Secondary Id
LX4211.203
Secondary Outcomes
Outcome Description
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. Percent change was calculated and is presented separately for each meal: i.e., breakfast, lunch and dinner. LS Means and CI for the Expansion groups were based on an ANCOVA model . LS Means and CI for the Pioneer Group were based on the arithmetic treatment mean.
Outcome Time Frame
Baseline, Day 3 to Day 27
Outcome Measure
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)
Outcome Description
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. LS Means and CI for the Expansion groups were based on an ANCOVA model. LS Means and CI for the Pioneer Group were based on the arithmetic treatment mean.
Outcome Time Frame
Baseline, Day 3 to Day 27
Outcome Measure
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)
Outcome Description
Baseline was defined as the last non-missing assessment prior to first dose of study drug. Change in FPG was calculated by subtracting baseline value from Day 29 value. LS Means and CI for the Expansion groups were based on a linear mixed repeated measures model.
Outcome Time Frame
Baseline, Day 29
Outcome Measure
Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29
Outcome Description
A MMTT with frequent blood sample collection and with urine collection was performed on Day 1 and Day 29. Participants fasted (with the exception of water or non-caffeinated, calorie-free beverages) for at least 8 hours before the start of the MMTT and until the final blood sample was collected. Study drug was to be given within 15 minutes before liquid "Boost® Original" breakfast. The area under the plasma concentration-time curve (AUC) from time-zero to 3h postdose on Day 1 and Day 29 was calculated using the linear-up/log-down trapezoidal rule. Change was calculated by subtracting Day 1 value from Day 29 value. LS Means and CI were based on a linear mixed model.
Outcome Time Frame
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
Outcome Measure
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
Outcome Description
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. Change in percent time per day spent in euglycemic range was calculated by subtracting baseline value from Day 29 value. LS Means and CI for the Expansion groups were based on a mixed model. LS mean and CI for the Pioneer Group were based on the arithmetic treatment mean.
Outcome Time Frame
Baseline, Day 3 to Day 27
Outcome Measure
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
Outcome Description
A MMTT with frequent blood sample collection and with urine collection was performed on Day 1 and Day 29. Participants fasted (with the exception of water or non-caffeinated, calorie-free beverages) for at least 8 hours before the start of the MMTT and until the final blood sample was collected. Study drug was to be given within 15 minutes before liquid "Boost® Original" breakfast. Participants were asked to void immediately before blood sample 15 minutes before start of mixed meal and immediately after the 180-minute (3 hour) blood sample was collected, and all urine between the -15 minute and post-180-minute time points was collected for urine glucose calculation. Change was calculated by subtracting Day 1 value from Day 29 value. LS Means were based on a linear mixed model.
Outcome Time Frame
From 15 minutes before start of mixed meal until 180 min post start of mixed meal, on Day 1 and Day 29
Outcome Measure
Change From Day 1 in 3-hour Urinary Glucose Excretion Following a Mixed Meal Tolerance Test (MMTT) to Day 29: Expansion Groups
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Maximum Age Number (converted to Years and rounded down)
55
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Rubina Heptulla
Investigator Email
RHEPTULL@montefiore.org
Investigator Phone
718-920-6542 / 718-920-5473/ 718-920-4664