inTandem4: Dose-ranging Study in Patients With Type 1 Diabetes Mellitus

• Sponsor: Lexicon Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02459899
• Collaborator: Sanofi (Industry)
• Enrollment: 141
• Locations: 17
• Arms: 4
• Actual Duration (Months): 13
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 141 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2b, Dose-ranging, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study in Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy
• Actual Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Drug: Placebo; Placebo, once daily, before the first meal of the day
Experimental: Sotagliflozin 75 mg Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally for 12 weeks.	Drug: Placebo; Placebo, once daily, before the first meal of the day; Drug: Sotagliflozin; Sotagliflozin,once daily, before the first meal of the day
Experimental: Sotagliflozin 200 mg Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally for 12 weeks.	Drug: Placebo; Placebo, once daily, before the first meal of the day; Drug: Sotagliflozin; Sotagliflozin,once daily, before the first meal of the day
Experimental: Sotagliflozin 400 mg Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally for 12 weeks.	Drug: Sotagliflozin; Sotagliflozin,once daily, before the first meal of the day

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Lexicon Investigational Site	Concord	California	United States	94520
2	Lexicon Investigational Site	Ventura	California	United States	93003
3	Lexicon Investigational Site	Denver	Colorado	United States	80209
4	Lexicon Investigational Site	Jacksonville	Florida	United States	32225
5	Lexicon Investigational Site	Miami	Florida	United States	33175
6	Lexicon Investigational Site	Springfield	Illinois	United States	62711
7	Lexicon Investigational Site	Metairie	Louisiana	United States	70006
8	Lexicon Investigational Site	Auburn	Maine	United States	04210
9	Lexicon Investigational Site	Rockville	Maryland	United States	20852
10	Lexicon Investigational Site	Great Falls	Montana	United States	59405
11	Lexicon Investigational Site	Omaha	Nebraska	United States	68114
12	Lexicon Investigational Site	High Point	North Carolina	United States	27265
13	Lexicon Investigational Site	Columbus	Ohio	United States	43213
14	Lexicon Investigational Site	San Antonio	Texas	United States	78229
15	Lexicon Investigational Site	Salt Lake City	Utah	United States	84107
16	Lexicon Investigational Site	Chesapeake	Virginia	United States	23321
17	Lexicon Investigational Site	Manassas	Virginia	United States	20110

Sponsors and Collaborators

• Lexicon Pharmaceuticals
• Sanofi

Investigators

• Study Director: Suman Wason, MD, Lexicon Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lexicon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02459899
• Other Study ID Numbers: LX4211.1-206-T1DM; LX4211.206
• First Posted: Jun 2, 2015
• 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 17 centers in the United States from 10 July 2015 to 26 August 2016.
Pre-assignment Detail	207 participants were screened and 141 participants with Type 1 diabetes mellitus who had inadequate glycemic control with insulin therapy alone, were randomized equally into four treatment groups: sotagliflozin 75 milligrams (mg), sotagliflozin 200 mg, sotagliflozin 400 mg or placebo.

Arm/Group Title	Placebo	Sotagliflozin 75 mg	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 12 weeks.
Period Title: Overall Study
STARTED	36	35	35	35
COMPLETED	33	29	35	33
NOT COMPLETED	3	6	0	2

Baseline Characteristics

Arm/Group Title	Placebo	Sotagliflozin 75 mg	Sotagliflozin 200 mg	Sotagliflozin 400 mg	Total
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 12 weeks.	Total of all reporting groups
Overall Participants	36	35	35	35	141
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.1 (11.29)	42.4 (12.01)	47.0 (14.01)	44.8 (15.36)	45.6 (13.29)
Sex: Female, Male (Count of Participants)
Female	21 58.3%	22 62.9%	15 42.9%	15 42.9%	73 51.8%
Male	15 41.7%	13 37.1%	20 57.1%	20 57.1%	68 48.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	1 2.8%	0 0%	1 2.9%	0 0%	2 1.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	4 11.4%	3 8.6%	0 0%	7 5%
White	34 94.4%	31 88.6%	31 88.6%	35 100%	131 92.9%
More than one race	1 2.8%	0 0%	0 0%	0 0%	1 0.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Body Weight (kilograms) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms]	91.92 (19.681)	79.97 (14.358)	82.90 (17.140)	86.95 (20.857)	85.48 (18.557)
Daily Total Insulin Dose (International units per kilogram (IU/kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [International units per kilogram (IU/kg)]	0.68 (0.306)	0.65 (0.229)	0.70 (0.298)	0.77 (0.409)	0.70 (0.315)
Hemoglobin A1C (A1c) (percentage of A1C) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of A1C]	7.95 (0.849)	8.00 (0.839)	8.07 (0.926)	8.05 (0.735)	8.02 (0.832)
Body Mass Index (kilograms per meter square) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilograms per meter square]	31.81 (5.763)	27.41 (5.016)	28.01 (4.707)	29.37 (5.849)	29.17 (5.569)
Duration of Diabetes (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.9 (13.51)	22.2 (13.04)	23.4 (13.17)	24.0 (14.96)	24.1 (13.66)
Insulin delivery method in Participants (Count of Participants)
continuous subcutaneous insulin infusion (CSII)	19 52.8%	18 51.4%	18 51.4%	18 51.4%	73 51.8%
multiple daily injection (MDI)	17 47.2%	17 48.6%	17 48.6%	17 48.6%	68 48.2%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1C (A1C) at Week 12
Description	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.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Analysis included participants from the mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Sotagliflozin 75 mg	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 12 weeks.
Measure Participants	33	29	35	33
Least Squares Mean (Standard Error) [percentage of A1C]	-0.35 (0.096)	-0.60 (0.100)	-0.84 (0.095)	-0.73 (0.096)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 75 mg
	Comments	Analysis was performed using 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 A1C-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments	Threshold for significance < 0.05
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.139
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	Analysis was performed using 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 A1C-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Threshold for significance < 0.05
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -0.75 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.135
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	Analysis was performed using 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 A1C-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments	Threshold for significance < 0.05
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.65 to -0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.136
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 12 in 2-Hour Postprandial Glucose (PPG) Following the Standardized Mixed Meal
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis included participants from the mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Sotagliflozin 75 mg	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 12 weeks.
Measure Participants	32	27	25	32
Least Squares Mean (Standard Error) [milligrams per deciliter (mg/dL)]	-0.2 (12.51)	-20.5 (13.66)	-27.6 (14.16)	-49.7 (12.51)

3. Secondary Outcome

Title	Absolute Change From Baseline in Body Weight to Week 12
Description	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.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Analysis included participants from the mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Sotagliflozin 75 mg	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 12 weeks.
Measure Participants	33	29	35	33
Least Squares Mean (Standard Error) [kilograms]	1.13 (0.425)	-0.16 (0.441)	-1.24 (0.417)	-1.48 (0.422)

4. Secondary Outcome

Title	Percent Change From Baseline in Body Weight to Week 12
Description	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.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Analysis included participants from the mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Sotagliflozin 75 mg	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 12 weeks.
Measure Participants	33	29	35	33
Least Squares Mean (Standard Error) [percent change]	1.26 (0.535)	0.11 (0.556)	-1.47 (0.531)	-1.61 (0.538)

5. Secondary Outcome

Title	Change From Baseline to Week 12 in 24-Hour Urinary Glucose Excretion
Description	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.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

Analysis included participants from the mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Sotagliflozin 75 mg	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 12 weeks.
Measure Participants	23	24	23	24
Least Squares Mean (Standard Error) [grams per day]	0.2555 (10.53532)	42.0185 (10.52465)	57.9850 (10.51367)	70.7058 (10.28691)

6. Secondary Outcome

Title	Change From Baseline to Week 12 in Fasting Plasma Glucose
Description	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.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

Analysis included participants from the mITT population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Sotagliflozin 75 mg	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally for 12 weeks.	Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 12 weeks.
Measure Participants	33	29	34	33
Least Squares Mean (Standard Error) [mg/dL]	-10.8 (8.99)	-19.4 (9.55)	-19.8 (8.85)	-32.2 (8.99)

Adverse Events

Time Frame	Adverse event (AE) data were collected from first dose up to 30 days after date of last dose of double-blind study treatment (up to 114 days)
Adverse Event Reporting Description	Analysis was performed on safety population which included all randomized participants who had received at least 1 dose of study drug.
Arm/Group Title	Placebo		Sotagliflozin 75 mg		Sotagliflozin 200 mg		Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, for 12 weeks.		Sotagliflozin 75 mg (one 75 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.		Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 12 weeks.		Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 12 weeks.
All Cause Mortality
	Placebo		Sotagliflozin 75 mg		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/35 (0%)		0/35 (0%)		0/35 (0%)
Serious Adverse Events
	Placebo		Sotagliflozin 75 mg		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)		1/35 (2.9%)		1/35 (2.9%)		1/35 (2.9%)
Ear and labyrinth disorders
Deafness neurosensory	1/36 (2.8%)	1	0/35 (0%)	0	0/35 (0%)	0	0/35 (0%)	0
Injury, poisoning and procedural complications
Fibula fracture	0/36 (0%)	0	1/35 (2.9%)	1	0/35 (0%)	0	0/35 (0%)	0
Tibia fracture	0/36 (0%)	0	1/35 (2.9%)	1	0/35 (0%)	0	0/35 (0%)	0
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/36 (0%)	0	0/35 (0%)	0	1/35 (2.9%)	1	1/35 (2.9%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Sotagliflozin 75 mg		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/36 (27.8%)		5/35 (14.3%)		6/35 (17.1%)		4/35 (11.4%)
Gastrointestinal disorders
Abdominal discomfort	0/36 (0%)	0	0/35 (0%)	0	0/35 (0%)	0	2/35 (5.7%)	2
Constipation	2/36 (5.6%)	2	0/35 (0%)	0	0/35 (0%)	0	0/35 (0%)	0
Diarrhoea	3/36 (8.3%)	3	0/35 (0%)	0	1/35 (2.9%)	1	1/35 (2.9%)	1
Infections and infestations
Nasopharyngitis	2/36 (5.6%)	2	2/35 (5.7%)	2	2/35 (5.7%)	2	0/35 (0%)	0
Sinusitis	4/36 (11.1%)	6	2/35 (5.7%)	2	0/35 (0%)	0	0/35 (0%)	0
Upper respiratory tract infection	0/36 (0%)	0	0/35 (0%)	0	2/35 (5.7%)	2	0/35 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/36 (0%)	0	0/35 (0%)	0	2/35 (5.7%)	2	0/35 (0%)	0
Cough	1/36 (2.8%)	1	3/35 (8.6%)	3	0/35 (0%)	0	1/35 (2.9%)	1

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.