Clinical trial NCT01742208: Safety and Efficacy of Sotagliflozin (LX4211) in Patients With Inadequately Controlled Type 1 Diabetes Mellitus
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Lexicon Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2012-12-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Percent Change From Baseline in Total Daily Bolus Amount of Exogenous Insulin Required Calculated Over Days 3 to 27 (Treatment Outpatient Period)
timeFrame: Baseline, Day 3 to Day 27
Secondary outcomes:
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)
timeFrame: Baseline, Day 3 to Day 27
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)
timeFrame: Baseline, Day 3 to Day 27
measure: Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29
timeFrame: Baseline, Day 29
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
timeFrame: 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
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
timeFrame: Baseline, Day 3 to Day 27
measure: Change From Day 1 in 3-hour Urinary Glucose Excretion Following a Mixed Meal Tolerance Test (MMTT) to Day 29: Expansion Groups
timeFrame: From 15 minutes before start of mixed meal until 180 min post start of mixed meal, on Day 1 and Day 29
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Lexicon Investigational Site
state: Colorado
city: Atlanta
country: United States
facility: Lexicon Investigational Site
state: Georgia
city: Baton Rouge
country: United States
facility: Lexicon Investigational Site
state: Louisiana
city: Omaha
country: United States
facility: Lexicon Investigational Site
state: Nebraska
city: Bronx
country: United States
facility: Lexicon Investigational Site
state: New York
city: Durham
country: United States
facility: Lexicon Investigational Site
state: North Carolina
city: Dallas
country: United States
facility: Lexicon Investigational Site
state: Texas
Study officials:
affiliation: Lexicon Pharmaceuticals, Inc.
name: Paul Strumph, M.D.
role: STUDY_DIRECTOR
References:
citation: Sands AT, Zambrowicz BP, Rosenstock J, Lapuerta P, Bode BW, Garg SK, Buse JB, Banks P, Heptulla R, Rendell M, Cefalu WT, Strumph P. Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes. Diabetes Care. 2015 Jul;38(7):1181-8. doi: 10.2337/dc14-2806. Epub 2015 Jun 6.