Safety and Efficacy of Sotagliflozin (LX4211) in Patients With Inadequately Controlled Type 1 Diabetes Mellitus

• Sponsor: Lexicon Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01742208
• Collaborator: Sanofi (Industry)
• Enrollment: 36
• Locations: 7
• Arms: 3
• Actual Duration (Months): 11
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus	Drug: Sotagliflozin; Drug: Placebo; Drug: Sotagliflozin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Feb 1, 2013
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sotagliflozin 400 mg - Pioneer Group Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.	Drug: Sotagliflozin; Participants received sotagliflozin once daily for 29 days. Pioneer Group participants were to have completed dosing prior to any study drug administration in Expansion Groups.; Other Names: LX4211
Placebo Comparator: Placebo - Expansion Group Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Drug: Placebo; Participants received placebo-matching sotagliflozin tablets once daily for 29 days.
Experimental: Sotagliflozin 400 mg - Expansion Group Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.	Drug: Sotagliflozin; Participants received sotagliflozin once daily for 29 days; pioneer participants completed dosing prior to dosing any other study participants.; Other Names: LX4211

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Total Daily Bolus Amount of Exogenous Insulin Required Calculated Over Days 3 to 27 (Treatment Outpatient Period) [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 Outcome Measures

1. 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]

   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.

2. 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]

   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.

3. Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29 [Baseline, Day 29]

   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.

4. 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]

   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.

5. 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]

   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.

6. 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]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lexicon Investigational Site	Aurora	Colorado	United States	80045
2	Lexicon Investigational Site	Atlanta	Georgia	United States	30318
3	Lexicon Investigational Site	Baton Rouge	Louisiana	United States	70808
4	Lexicon Investigational Site	Omaha	Nebraska	United States	68131
5	Lexicon Investigational Site	Bronx	New York	United States	10467
6	Lexicon Investigational Site	Durham	North Carolina	United States	27713
7	Lexicon Investigational Site	Dallas	Texas	United States	75230

Sponsors and Collaborators

• Lexicon Pharmaceuticals
• Sanofi

Investigators

• Study Director: Paul Strumph, M.D., Lexicon Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lexicon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01742208
• Other Study ID Numbers: LX4211.1-203-T1DM; LX4211.203
• First Posted: Dec 5, 2012
• Last Update Posted: Feb 12, 2020
• Last Verified: Feb 1, 2020

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Study Results

Participant Flow

Recruitment Details	The study was conducted at 7 sites in United States between 08 February 2013 and 13 January 2014. A total of 36 participants were enrolled and treated in the study which consisted of 2 groups: Pioneer Group and Expansion Groups.
Pre-assignment Detail	In this study, first 3 participants (Pioneer Group) received open-label sotagliflozin. Once dosing was completed in Pioneer Group, 33 different participants were randomized in 1:1 ratio to Expansion groups (sotagliflozin or placebo). Randomization was stratified according to baseline glycosylated hemoglobin (A1C [<=8 percent {%} vs. >8%]).

Arm/Group Title	Sotagliflozin 400 mg - Pioneer Group	Placebo - Expansion Group	Sotagliflozin 400 mg - Expansion Group
Arm/Group Description	Sotagliflozin 400 milligram (mg) (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.	Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Period Title: Overall Study
STARTED	3	17	16
COMPLETED	3	17	16
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Sotagliflozin 400 mg - Pioneer Group	Placebo - Expansion Group	Sotagliflozin 400 mg - Expansion Group	Total
Arm/Group Description	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.	Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.	Total of all reporting groups
Overall Participants	3	17	16	36
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.3 (2.08)	35.6 (11.75)	38.8 (12.11)	36.8 (11.39)
Sex: Female, Male (Count of Participants)
Female	2 66.7%	9 52.9%	8 50%	19 52.8%
Male	1 33.3%	8 47.1%	8 50%	17 47.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	2 11.8%	0 0%	2 5.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 33.3%	0 0%	0 0%	1 2.8%
White	2 66.7%	14 82.4%	16 100%	32 88.9%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 5.9%	0 0%	1 2.8%
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	172.3 (8.5)	170.5 (11.7)	169.5 (12.2)	170.2 (11.5)
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	84.5 (19.2)	76.8 (15.5)	78.4 (14.8)	78.1 (15.1)
Insulin Therapy (Count of Participants)
Multiple Daily Injections (MDI)	0 0%	5 29.4%	6 37.5%	11 30.6%
Continuous Subcutaneous Insulin Infusion (CSII)	3 100%	12 70.6%	10 62.5%	25 69.4%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Total Daily Bolus Amount of Exogenous Insulin Required Calculated Over Days 3 to 27 (Treatment Outpatient Period)
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.
Time Frame	Baseline, Day 3 to Day 27

Outcome Measure Data

Analysis Population Description

Analysis was performed using ITT population. Here, overall number of participants analyzed=participants with available data for this outcome measure.

Arm/Group Title	Sotagliflozin 400 mg - Pioneer Group	Placebo - Expansion Group	Sotagliflozin 400 mg - Expansion Group
Arm/Group Description	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.	Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Measure Participants	3	17	15
Least Squares Mean (95% Confidence Interval) [percent change]	-46.32	-7.00	-32.14

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo - Expansion Group, Sotagliflozin 400 mg - Expansion Group
	Comments	Between-group comparison of the 2 Expansion Groups was based on an ANCOVA model with covariates of baseline mean total daily bolus insulin, treatment group, factor used to stratify the randomization (screening A1C <= 8%, > 8%), and random effect of participant*treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-25.14
	Confidence Interval	(2-Sided) 95%; -42.78 to -7.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference is sotagliflozin - placebo

2. Secondary Outcome

Title	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)
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.
Time Frame	Baseline, Day 3 to Day 27

Outcome Measure Data

Analysis Population Description

Analysis was performed using ITT population. Here, number analyzed=participants with available data for this outcome measure.

Arm/Group Title	Sotagliflozin 400 mg - Pioneer Group	Placebo - Expansion Group	Sotagliflozin 400 mg - Expansion Group
Arm/Group Description	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.	Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Measure Participants	3	17	16
Before Breakfast	-42.19	10.79	-25.16
Before Lunch	-59.02	3.94	-25.85
Before Dinner	-34.83	33.34	-24.02

3. Secondary Outcome

Title	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)
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.
Time Frame	Baseline, Day 3 to Day 27

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed=participants with available data for this outcome measure.

Arm/Group Title	Sotagliflozin 400 mg - Pioneer Group	Placebo - Expansion Group	Sotagliflozin 400 mg - Expansion Group
Arm/Group Description	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.	Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Measure Participants	3	17	15
Least Squares Mean (95% Confidence Interval) [percent change]	-27.00	-1.20	-15.52

4. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Day 29
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.
Time Frame	Baseline, Day 29

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Sotagliflozin 400 mg - Pioneer Group	Placebo - Expansion Group	Sotagliflozin 400 mg - Expansion Group
Arm/Group Description	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.	Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Measure Participants	3	17	16
Least Squares Mean (95% Confidence Interval) [milligram/deciliter (mg/dL)]	-54.2	10.0	-12.5

5. Secondary Outcome

Title	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
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.
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 Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed=participants with available data for this outcome measure. Data for this outcome measure was not analyzed for Pioneer Group participants.

Arm/Group Title	Placebo - Expansion Group	Sotagliflozin 400 mg - Expansion Group
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Measure Participants	16	16
Least Squares Mean (95% Confidence Interval) [mg*h/dL]	-140.83	-308.51

6. Secondary Outcome

Title	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
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.
Time Frame	Baseline, Day 3 to Day 27

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed=participants with available data for this outcome measure.

Arm/Group Title	Sotagliflozin 400 mg - Pioneer Group	Placebo - Expansion Group	Sotagliflozin 400 mg - Expansion Group
Arm/Group Description	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.	Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Measure Participants	3	15	13
Least Squares Mean (95% Confidence Interval) [percent time per day]	6.6	-1.2	11.1

7. Secondary Outcome

Title	Change From Day 1 in 3-hour Urinary Glucose Excretion Following a Mixed Meal Tolerance Test (MMTT) to Day 29: Expansion Groups
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.
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 Data

Analysis Population Description

Analysis was performed on ITT population. Here, overall number of participants analyzed=participants with available data for this outcome measure. Data for this outcome measure was not analyzed for Pioneer Group participants.

Arm/Group Title	Placebo - Expansion Group	Sotagliflozin 400 mg - Expansion Group
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
Measure Participants	13	16
Least Squares Mean (95% Confidence Interval) [gram per 3 hour]	-6.34	8.30

Adverse Events

Time Frame	All Adverse Events (AEs) were collected from Day 1 until the end of study (up to 40 days ).
Adverse Event Reporting Description	Safety population included all participants who were randomized and received at least 1 dose of study drug. Participants in this population were assigned to the treatment group as they were treated on Day 1.
Arm/Group Title	Sotagliflozin 400 mg - Pioneer Group		Placebo - Expansion Group		Sotagliflozin 400 mg - Expansion Group
Arm/Group Description	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; open label administration.		Two placebo-matching sotagliflozin tablets, once daily, orally, before breakfast for 29 days; double-blind administration.		Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before breakfast for 29 days; double-blind administration.
All Cause Mortality
	Sotagliflozin 400 mg - Pioneer Group		Placebo - Expansion Group		Sotagliflozin 400 mg - Expansion Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/17 (0%)		0/16 (0%)
Serious Adverse Events
	Sotagliflozin 400 mg - Pioneer Group		Placebo - Expansion Group		Sotagliflozin 400 mg - Expansion Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/17 (0%)		2/16 (12.5%)
Metabolism and nutrition disorders
DIABETIC KETOACIDOSIS	0/3 (0%)	0	0/17 (0%)	0	2/16 (12.5%)	2
Other (Not Including Serious) Adverse Events
	Sotagliflozin 400 mg - Pioneer Group		Placebo - Expansion Group		Sotagliflozin 400 mg - Expansion Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		12/17 (70.6%)		14/16 (87.5%)
Blood and lymphatic system disorders
LEUKOCYTOSIS	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
Ear and labyrinth disorders
VERTIGO	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
Gastrointestinal disorders
ABDOMINAL DISCOMFORT	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
ABDOMINAL DISTENSION	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
ABDOMINAL PAIN	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
ABDOMINAL PAIN UPPER	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
ABNORMAL FAECES	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
COLITIS	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
DIARRHOEA	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
DYSPEPSIA	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	2
FAECES HARD	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
FLATULENCE	0/3 (0%)	0	1/17 (5.9%)	1	1/16 (6.3%)	1
NAUSEA	1/3 (33.3%)	2	1/17 (5.9%)	1	4/16 (25%)	4
VOMITING	0/3 (0%)	0	1/17 (5.9%)	1	2/16 (12.5%)	2
General disorders
INFLUENZA LIKE ILLNESS	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
PYREXIA	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
Infections and infestations
CYSTITIS	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
FUNGAL SKIN INFECTION	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
GASTROENTERITIS	0/3 (0%)	0	0/17 (0%)	0	2/16 (12.5%)	2
LICE INFESTATION	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
LOCALISED INFECTION	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
NAIL INFECTION	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
NASOPHARYNGITIS	0/3 (0%)	0	2/17 (11.8%)	2	2/16 (12.5%)	2
SINUSITIS	0/3 (0%)	0	1/17 (5.9%)	1	1/16 (6.3%)	1
SKIN INFECTION	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
UPPER RESPIRATORY TRACT INFECTION	0/3 (0%)	0	1/17 (5.9%)	1	1/16 (6.3%)	1
Injury, poisoning and procedural complications
EXCORIATION	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED	0/3 (0%)	0	2/17 (11.8%)	2	0/16 (0%)	0
Metabolism and nutrition disorders
DECREASED APPETITE	0/3 (0%)	0	0/17 (0%)	0	2/16 (12.5%)	2
Musculoskeletal and connective tissue disorders
MYALGIA	1/3 (33.3%)	1	0/17 (0%)	0	0/16 (0%)	0
Nervous system disorders
AMNESIA	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
DIZZINESS	1/3 (33.3%)	1	0/17 (0%)	0	1/16 (6.3%)	1
HEADACHE	1/3 (33.3%)	1	2/17 (11.8%)	2	3/16 (18.8%)	3
MIGRAINE	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
SINUS HEADACHE	0/3 (0%)	0	0/17 (0%)	0	2/16 (12.5%)	2
Renal and urinary disorders
ACUTE PRERENAL FAILURE	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
NEPHROLITHIASIS	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
NOCTURIA	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
POLLAKIURIA	1/3 (33.3%)	1	0/17 (0%)	0	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
Skin and subcutaneous tissue disorders
HYPERHIDROSIS	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
RASH	0/3 (0%)	0	1/17 (5.9%)	1	0/16 (0%)	0
RASH ERYTHEMATOUS	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
SKIN IRRITATION	0/3 (0%)	0	2/17 (11.8%)	2	0/16 (0%)	0
Surgical and medical procedures
NAIL OPERATION	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	1
Vascular disorders
HYPOTENSION	0/3 (0%)	0	0/17 (0%)	0	1/16 (6.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.