SOTA-BONE: Efficacy and Bone Safety of Sotagliflozin 400 and 200 mg Versus Placebo in Participants With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control

• Sponsor: Lexicon Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03386344
• Collaborator: Sanofi (Industry)
• Enrollment: 376
• Locations: 53
• Arms: 3
• Actual Duration (Months): 27.3
• Patients Per Site: 7.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective is to demonstrate the superiority of Sotagliflozin 400 milligrams (mg) versus placebo with respect to hemoglobin A1c (Hb1Ac) reduction in participants with type 2 diabetes (T2D) who have inadequate glycemic control on diet and exercise only or with a stable antidiabetes regimen.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Sotagliflozin; Drug: Placebo	Phase 3

Detailed Description

Study duration per participant is approximately 110 weeks (Screening period of up to 2 weeks, 2 week single-blind run-in period), a 26-week double-blind core treatment period, a 78-week double-blind extension period, and a 2- week post treatment follow up period.

Dual-energy X-ray absorptiometry (DXA) scans will be performed to assess Bone Mineral Density and Fat vs. Lean body mass at baseline and Weeks 26, 52, and 104.

Study Design

• Study Type: Interventional
• Actual Enrollment: 376 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 26-week Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, Phase 3 Study With a 78-week Extension Period to Evaluate the Efficacy and Bone Safety of Sotagliflozin in Patients 55 Years or Older With Type 2 Diabetes Mellitus and Inadequate Glycemic Control
• Actual Study Start Date: Feb 19, 2018
• Actual Primary Completion Date: May 22, 2019
• Actual Study Completion Date: May 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Drug: Placebo; Pharmaceutical form: Tablet; Route of administration: Oral
Experimental: Sotagliflozin 200 mg Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Drug: Sotagliflozin; Pharmaceutical form: Tablet; Route of administration: Oral; Other Names: SAR439954 ; Drug: Placebo; Pharmaceutical form: Tablet; Route of administration: Oral
Experimental: Sotagliflozin 400 mg Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Drug: Sotagliflozin; Pharmaceutical form: Tablet; Route of administration: Oral; Other Names: SAR439954

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26 [Baseline to Week 26]

   An analysis of covariance (ANCOVA) model is used for analysis.

Secondary Outcome Measures

1. Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Week 26 [Baseline to Week 26]

   An ANCOVA model is used for analysis.

2. Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Week 26 [Baseline to Week 26]

   An ANCOVA model is used for analysis.

3. Percent Change From Baseline in Bone Mineral Density (BMD) of Femoral Neck at Week 26 [Baseline to Week 26]

   An ANCOVA model is used for analysis.

4. Change From Baseline in Body Weight at Week 26 [Baseline to Week 26]

   An ANCOVA model is used for analysis.

5. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 [Baseline to Week 26]

   An ANCOVA model is used for analysis.

6. Change From Baseline in Systolic Blood Pressure (SBP) at Week 12 [Baseline to Week 12]

   An ANCOVA model is used for analysis.

7. Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% at Week 26 [Week 26]

8. Percentage of Participants With Adverse Events (AEs) [up to 106 weeks]

   An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria :

• Participants with T2D managed with diet and exercise only or with a stable antidiabetes regimen (in monotherapy or combination therapy that can include oral antidiabetes medications, insulin, or glucagon-like peptide-1 agonists) for more than 12 weeks.

• Participants has given written informed consent to participate in the study in accordance with local regulations.

Exclusion criteria:

• Age <55 years.

• Women who have been postmenopausal (or undergone bilateral oophorectomy) for less than 5 years.

• Type 1 diabetes mellitus.

• Body mass index (BMI) ≤20 or >45 kilogram per meter square kg/m^2 or bodyweight that exceeds the weight limits of the DXA scanner.

• Hemoglobin A1C (HbA1c) <7.0% or HbA1c >11.0%.

• Use of a selective sodium-glucose cotransporter type 2 (SGLT2) inhibitor or thiazolidinedione within 24 months.

• Bone mineral density (BMD) T- score <-2.0 at any site (ie, lumbar spine, total hip, or femoral neck).

• History of fracture within 12 months (except for fractures of the hand/fingers, foot/toes, facial bones, and skull).

• Treatment with medications known to affect bone mass or modify the risk of fractures within 36 months (eg, bisphosphonates, selective estrogen receptor modulators, calcitonin, teriparatide, denosumab, strontium ranelate, growth hormone, aromatase inhibitors, androgen deprivation therapy, carbamazepine, phenytoin, and phenobarbital). Use of hormonal replacement that includes systemic or transdermal estrogen or testosterone is excluded unless is stable for at least 24 months prior to Screening.

• Lower extremity complications (such as skin ulcers, infection, osteomyelitis and gangrene) identified during the Screening period, and still requiring treatment at randomization.

• Uncontrolled high blood pressure, severe anemia, severe cardiovascular problems, such as heart failure, active cancer, or other conditions that the Investigator believes with result in a short life expectancy.

• Renal disease as defined by an estimated glomerular filtration rate (eGFR) <30 milliliter per minute (mL/min)/1.73 meter square (m^2) at the Screening Visit by the 4 variable Modification of Diet in Renal Disease equation.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 8409009	Escondido	California	United States	92025
2	Investigational Site Number 8409010	Greenbrae	California	United States	94904
3	Investigational Site Number 8409005	Walnut Creek	California	United States	94598
4	Investigational Site Number 8409012	Columbus	Georgia	United States	31904
5	Investigational Site Number 8409011	Evansville	Indiana	United States	47714-8011
6	Investigational Site Number 8409014	Wichita	Kansas	United States	67205-1138
7	Investigational Site Number 8409015	Albuquerque	New Mexico	United States	87106
8	Investigational Site Number 8409002	Chapel Hill	North Carolina	United States	27517
9	Investigational Site Number 8409001	Wilmington	North Carolina	United States	28401-6638
10	Investigational Site Number 8409008	Dayton	Ohio	United States	45419-4336
11	Investigational Site Number 8409004	Chattanooga	Tennessee	United States	37404
12	Investigational Site Number 8409013	Austin	Texas	United States	78749
13	Investigational Site Number 8409003	Dallas	Texas	United States	75230
14	Investigational Site Number 8409007	Katy	Texas	United States	77450
15	Investigational Site Number 0369003	Fremantle		Australia	6160
16	Investigational Site Number 0369002	Merewether		Australia	2291
17	Investigational Site Number 0369004	Parkville		Australia	3050
18	Investigational Site Number 1249003	Brampton		Canada	L6S 0C6
19	Investigational Site Number 1249008	Etobicoke		Canada	M9R 4E1
20	Investigational Site Number 1249005	Pointe-Claire		Canada	H9R 4S3
21	Investigational Site Number 1249006	Thornhill		Canada	L4J 1W3
22	Investigational Site Number 1249004	Thornhill		Canada	L4J 8L7
23	Investigational Site Number 1249007	Vancouver		Canada	V5Y 3W2
24	Investigational Site Number 1249002	Victoriaville		Canada	G6P 6P6
25	Investigational Site Number 4109006	Daejeon		Korea, Republic of	35233
26	Investigational Site Number 4109005	Guri-Si, Gyeonggi-Do		Korea, Republic of	11923
27	Investigational Site Number 4109003	Gyeonggi-Do		Korea, Republic of	13620
28	Investigational Site Number 4109004	Seoul		Korea, Republic of	03722
29	Investigational Site Number 4109001	Seoul		Korea, Republic of	1830
30	Investigational Site Number 4849006	Aguascalientes, Aguascalientes		Mexico	20230
31	Investigational Site Number 4849001	Aguascalientes		Mexico	20129
32	Investigational Site Number 4849003	Cuernavaca		Mexico	62250
33	Investigational Site Number 4849002	Guadalajara Jalisco		Mexico	44130
34	Investigational Site Number 4849004	Monterrey		Mexico	64460
35	Investigational Site Number 4849005	Xalapa		Mexico	91020
36	Investigational Site Number 5549004	Auckland		New Zealand	1309
37	Investigational Site Number 5549003	Christchurch		New Zealand	8011
38	Investigational Site Number 5549001	Rotorua		New Zealand	3010
39	Investigational Site Number 5549002	Wellington		New Zealand	6021
40	Investigational Site Number 6439007	Kemerovo		Russian Federation	650002
41	Investigational Site Number 6439005	Novosibirsk		Russian Federation	630091
42	Investigational Site Number 6439002	Saint-Petersburg		Russian Federation	195213
43	Investigational Site Number 6439003	Saint-Petersburg		Russian Federation	196601
44	Investigational Site Number 6439001	St. Petersburg		Russian Federation	194358
45	Investigational Site Number 6439006	Yaroslavl		Russian Federation	150003
46	Investigational Site Number 1589005	Changhua		Taiwan	500
47	Investigational Site Number 1589008	New Taipei City		Taiwan	220
48	Investigational Site Number 1589006	Taichung		Taiwan	402
49	Investigational Site Number 1589007	Taichung		Taiwan	43303
50	Investigational Site Number 1589001	Tainan		Taiwan	710
51	Investigational Site Number 1589002	Tainan		Taiwan
52	Investigational Site Number 1589004	Taipei		Taiwan	100
53	Investigational Site Number 1589003	Taipei		Taiwan	11217

Sponsors and Collaborators

• Lexicon Pharmaceuticals
• Sanofi

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Nov 14, 2017
• Statistical Analysis Plan - Jan 31, 2020

More Information

Publications

None provided.

• Responsible Party: Lexicon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03386344
• Other Study ID Numbers: EFC15294; 2017-002041-30; U1111-1195-6371
• First Posted: Dec 29, 2017
• Last Update Posted: Jun 25, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; (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	Participants took part in the study at 53 investigative sites in the United States, Australia, Canada, Korea, Republic of Mexico, New Zealand, Russian Federation, and Taiwan from 19 February 2018 to 30 May 2020.
Pre-assignment Detail	Participants with a diagnosis of Type 2 Diabetes Mellitus (DM), were enrolled in 1 of 3 treatment groups: Placebo, Sotagliflozin 200 milligrams (mg) or Sotagliflozin 400 mg.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Period Title: Overall Study
STARTED	126	125	125
COMPLETED	9	9	9
NOT COMPLETED	117	116	116

Baseline Characteristics

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg	Total
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Total of all reporting groups
Overall Participants	126	125	125	376
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.3 (5.7)	66.1 (6.7)	66.5 (6.9)	66.3 (6.5)
Sex: Female, Male (Count of Participants)
Female	56 44.4%	56 44.8%	55 44%	167 44.4%
Male	70 55.6%	69 55.2%	70 56%	209 55.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	23 18.3%	21 16.8%	23 18.4%	67 17.8%
Not Hispanic or Latino	102 81%	104 83.2%	102 81.6%	308 81.9%
Unknown or Not Reported	1 0.8%	0 0%	0 0%	1 0.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1.6%	1 0.8%	3 2.4%	6 1.6%
Asian	26 20.6%	25 20%	24 19.2%	75 19.9%
Native Hawaiian or Other Pacific Islander	0 0%	3 2.4%	3 2.4%	6 1.6%
Black or African American	8 6.3%	8 6.4%	6 4.8%	22 5.9%
White	88 69.8%	87 69.6%	88 70.4%	263 69.9%
More than one race	2 1.6%	0 0%	0 0%	2 0.5%
Unknown or Not Reported	0 0%	1 0.8%	1 0.8%	2 0.5%
Region of Enrollment (participants) [Number]
Austria	2 1.6%	8 6.4%	3 2.4%	13 3.5%
Canada	20 15.9%	17 13.6%	20 16%	57 15.2%
South Korea	8 6.3%	9 7.2%	7 5.6%	24 6.4%
Mexico	16 12.7%	14 11.2%	17 13.6%	47 12.5%
New Zealand	9 7.1%	9 7.2%	11 8.8%	29 7.7%
Russia	17 13.5%	14 11.2%	19 15.2%	50 13.3%
Taiwan	12 9.5%	9 7.2%	7 5.6%	28 7.4%
United States	42 33.3%	45 36%	41 32.8%	128 34%
Hemoglobin A1c (HbA1c) (percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of HbA1c]	8.38 (0.91)	8.32 (0.96)	8.32 (0.95)	8.34 (0.94)
Systolic Blood Pressure (SBP) (millimeter of mercury (mmHg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [millimeter of mercury (mmHg)]	133.04 (13.10)	131.48 (13.69)	134.65 (14.74)	133.06 (13.88)
Bone Mineral Density (BMD) T-score: Lumbar Spine (t-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [t-score]	0.69 (2.0)	0.70 (1.74)	0.88 (1.71)	0.76 (1.82)
BMD T-score: Total Hip (t-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [t-score]	0.13 (1.01)	0.00 (0.90)	0.24 (1.17)	0.12 (1.04)
BMD T-score: Femoral Neck (t-score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [t-score]	-0.69 (0.86)	-0.66 (0.88)	-0.46 (1.03)	-0.60 (0.93)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 26
Description	An analysis of covariance (ANCOVA) model is used for analysis.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-treat (ITT) population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Measure Participants	126	125	125
Least Squares Mean (Standard Error) [percentage of HbA1c]	-0.22 (0.080)	-0.66 (0.077)	-0.67 (0.079)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline HbA1c as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares (LS) Means
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -0.649 to -0.250
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.102
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline HbA1c as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -0.634 to -0.235
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.102
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) of Lumbar Spine at Week 26
Description	An ANCOVA model is used for analysis.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who had received at least one dose of investigational medicinal product (IMP). Missing data are imputed using a pattern-based imputation method.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Measure Participants	125	125	125
Least Squares Mean (Standard Error) [percent change]	0.37 (0.327)	0.13 (0.323)	0.22 (0.327)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	Percent change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline BMD as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5707
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -1.070 to 0.590
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.423
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	Percent change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline BMD as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7247
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.969 to 0.674
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.419
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) of Total Hip at Week 26
Description	An ANCOVA model is used for analysis.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who had received at least one dose of IMP. Missing data are imputed using a pattern-based imputation method.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Measure Participants	125	125	125
Least Squares Mean (Standard Error) [percent change]	-0.36 (0.259)	-0.22 (0.220)	-0.16 (0.223)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	Percent change from baseline to Week 26 was analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline lumbar spine as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6454
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.14
	Confidence Interval	(2-Sided) 95%; -0.462 to 0.745
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.308
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	Percent change from baseline to Week 26 was analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline lumbar spine as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5289
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -0.410 to 0.798
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.308
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From Baseline in Bone Mineral Density (BMD) of Femoral Neck at Week 26
Description	An ANCOVA model is used for analysis.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who had received at least one dose of IMP. Missing data are imputed using a pattern-based imputation method.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Measure Participants	125	125	125
Least Squares Mean (Standard Error) [percent change]	-0.94 (0.379)	-0.20 (0.332)	-0.62 (0.338)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	Percent change from baseline to Week 26 was analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline BMD as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1050
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; -0.157 to 1.654
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.462
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	Percent change from baseline to Week 26 was analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline BMD as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4804
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	0.32
	Confidence Interval	(2-Sided) 95%; -0.577 to 1.226
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.460
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 26
Description	An ANCOVA model is used for analysis.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Measure Participants	126	125	125
Least Squares Mean (Standard Error) [kilogram (kg)]	-0.46 (0.261)	-2.37 (0.258)	-2.16 (0.264)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline body weight as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-1.91
	Confidence Interval	(2-Sided) 95%; -2.568 to -1.252
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.336
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline body weight as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-1.70
	Confidence Interval	(2-Sided) 95%; -2.360 to -1.046
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.335
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
Description	An ANCOVA model is used for analysis.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Measure Participants	126	125	125
Least Squares Mean (Standard Error) [milligram per deciliter (mg/dL)]	-7.274 (3.6064)	-26.165 (3.4656)	-28.607 (3.5912)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, baseline fasting plasma glucose as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-18.891
	Confidence Interval	(2-Sided) 95%; -27.8605 to -9.9205
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.5766
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 26 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, baseline fasting plasma glucose as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-21.333
	Confidence Interval	(2-Sided) 95%; -30.3294 to -12.3360
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.5902
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) at Week 12
Description	An ANCOVA model is used for analysis.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures. Missing data are imputed using washout imputation method under the missing not at random framework.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Measure Participants	126	125	125
Least Squares Mean (Standard Error) [millimeter of mercury (mmHg)]	-0.80 (1.149)	-1.61 (1.130)	-1.97 (1.165)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5864
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-0.80
	Confidence Interval	(2-Sided) 95%; -3.705 to 2.095
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.480
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	The change from baseline to Week 12 was analyzed using an ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, >8.5%) at screening, randomization strata of sex (male, female), and country as fixed effects, and baseline SBP as a covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4315
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in LS Means
	Estimated Value	-1.16
	Confidence Interval	(2-Sided) 95%; -4.058 to 1.734
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.478
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Hemoglobin A1c (HbA1c) <7.0% at Week 26
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants, irrespective of compliance with the study protocol and procedures.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Measure Participants	126	125	125
Number [percentage of participants]	9.5 7.5%	20.0 16%	21.6 17.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	Percentage difference between treatment groups from randomization strata of HbA1c (≤8.5, >8.5%) at screening and randomization strata of sex (male, female) using Cochran-Mantel-Haenszel weights.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0172
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	10.5
	Confidence Interval	(2-Sided) 95%; 1.78 to 19.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	Percentage difference between treatment groups from randomization strata of HbA1c (≤8.5, >8.5%) at screening and randomization strata of sex (male, female) using Cochran-Mantel-Haenszel weights.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	12.0
	Confidence Interval	(2-Sided) 95%; 3.23 to 20.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants With Adverse Events (AEs)
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.
Time Frame	up to 106 weeks

Outcome Measure Data

Analysis Population Description

Safety population included all randomized participants who had received at least one dose of IMP.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.	Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
Measure Participants	125	125	125
Number [percentage of participants]	80.0 63.5%	82.4 65.9%	82.4 65.9%

Adverse Events

Time Frame	First dose of study drug to last dose of study drug (up to 104 weeks) + 2 weeks
Adverse Event Reporting Description	The safety population included all randomized participants who had received at least one dose of IMP.
Arm/Group Title	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
Arm/Group Description	Following a 2 week run-in period, participants were randomized to matching placebo to sotagliflozin administered as 2 tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 106 weeks.		Following a 2 week run-in period, participants were randomized to Sotagliflozin 200 mg administered as 1 sotagliflozin tablet and 1 matching placebo tablet, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.		Following a 2 week run-in period, participants were randomized to Sotagliflozin 400 mg administered as two 200 mg sotagliflozin tablets, once daily, before the first meal of the day, for up to 26 weeks in the Core Treatment Period. Participants were eligible to continue treatment in the Extension Period. The total treatment duration was planned for up to 104 weeks.
All Cause Mortality
	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Serious Adverse Events
	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/125 (16%)		10/125 (8%)		9/125 (7.2%)
Cardiac disorders
Acute myocardial infarction	1/125 (0.8%)		0/125 (0%)		1/125 (0.8%)
Angina pectoris	0/125 (0%)		1/125 (0.8%)		1/125 (0.8%)
Cardiac disorder	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Cardiac failure congestive	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Coronary artery disease	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Myocardial infarction	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Ear and labyrinth disorders
Sudden hearing loss	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Vertigo positional	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Gastrointestinal disorders
Food poisoning	0/125 (0%)		0/125 (0%)		1/125 (0.8%)
Gastric ulcer	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Large intestine polyp	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Pancreatitis acute	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Rectal haemorrhage	0/125 (0%)		0/125 (0%)		1/125 (0.8%)
General disorders
Pyrexia	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Infections and infestations
Localised infection	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Pneumonia	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Post procedural infection	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Pyelonephritis	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Sepsis	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Staphylococcal infection	0/125 (0%)		0/125 (0%)		1/125 (0.8%)
Viral upper respiratory tract infection	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Injury, poisoning and procedural complications
Ankle fracture	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Hip fracture	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Maisonneuve fracture	0/125 (0%)		0/125 (0%)		1/125 (0.8%)
Road traffic accident	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Subdural haematoma	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Spinal compression fracture	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Investigations
Alanine aminotransferase increased	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Hypoglycaemia	2/125 (1.6%)		0/125 (0%)		0/125 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Foot deformity	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Lumbar spinal stenosis	0/125 (0%)		0/125 (0%)		1/125 (0.8%)
Osteoarthritis	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Bladder cancer	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Breast cancer female	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Colon cancer	0/125 (0%)		0/125 (0%)		1/125 (0.8%)
Metastatic malignant melanoma	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Pancreatic carcinoma	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Prostate cancer	0/125 (0%)		0/125 (0%)		1/125 (0.8%)
Rectal adenocarcinoma	0/125 (0%)		0/125 (0%)		1/125 (0.8%)
Renal cancer	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Squamous cell carcinoma	0/125 (0%)		0/125 (0%)		1/125 (0.8%)
Squamous cell carcinoma of head and neck	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Squamous cell carcinoma of skin	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Squamous cell carcinoma of the oral cavity	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Nervous system disorders
Hypoaesthesia	0/125 (0%)		1/125 (0.8%)		0/125 (0%)
Spinal claudication	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Renal and urinary disorders
Calculus bladder	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Ureterolithiasis	1/125 (0.8%)		0/125 (0%)		0/125 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/125 (0.8%)		1/125 (0.8%)		0/125 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/125 (52.8%)		67/125 (53.6%)		68/125 (54.4%)
Gastrointestinal disorders
Diarrhoea	7/125 (5.6%)		6/125 (4.8%)		16/125 (12.8%)
Infections and infestations
Influenza	2/125 (1.6%)		11/125 (8.8%)		5/125 (4%)
Nasopharyngitis	12/125 (9.6%)		9/125 (7.2%)		11/125 (8.8%)
Upper respiratory tract infection	24/125 (19.2%)		15/125 (12%)		3/125 (2.4%)
Urinary tract infection	15/125 (12%)		11/125 (8.8%)		14/125 (11.2%)
Injury, poisoning and procedural complications
Fall	9/125 (7.2%)		4/125 (3.2%)		7/125 (5.6%)
Investigations
Bone density decreased	5/125 (4%)		10/125 (8%)		7/125 (5.6%)
Metabolism and nutrition disorders
Vitamin D deficiency	9/125 (7.2%)		12/125 (9.6%)		7/125 (5.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/125 (1.6%)		8/125 (6.4%)		10/125 (8%)
Back pain	9/125 (7.2%)		5/125 (4%)		5/125 (4%)
Nervous system disorders
Headache	8/125 (6.4%)		3/125 (2.4%)		5/125 (4%)
Renal and urinary disorders
Pollakiuria	1/125 (0.8%)		7/125 (5.6%)		3/125 (2.4%)
Vascular disorders
Hypertension	7/125 (5.6%)		2/125 (1.6%)		5/125 (4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Institution must provide any proposed publication or presentation to Sponsor for Sponsor's review, comment and approval at least thirty (30) days prior to the proposed submission for publication date or the proposed presentation date. Sponsor shall have the right to have deleted from the final version of the publication any confidential information, proprietary information, or patentable subject matter.