inTandem2: Efficacy, Safety, and Tolerability Study of Sotagliflozin as Adjunct Therapy in Adult Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy

• Sponsor: Lexicon Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02421510
• Collaborator: Sanofi (Industry)
• Enrollment: 782
• Locations: 96
• Arms: 3
• Actual Duration (Months): 25.8
• Patients Per Site: 8.1
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This Phase 3 study was intended to demonstrate superiority of either Sotagliflozin high dose or low dose versus placebo on glycosylated hemoglobin A1C (A1C) reduction at Week 24 when used as an adjunct in adult participants with type 1 diabetes mellitus (T1D) who have inadequate glycemic control with insulin therapy.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus	Drug: Sotagliflozin; Drug: Sotagliflozin; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 782 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of LX4211 as Adjunct Therapy in Adult Patients With Type 1 Diabetes Mellitus Who Have Inadequate Glycemic Control With Insulin Therapy
• Actual Study Start Date: May 1, 2015
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Jun 23, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Drug: Placebo; Placebo, once daily, before the first meal of the day
Experimental: Sotagliflozin 200 mg Sotagliflozin 200 milligram (mg) (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Drug: Sotagliflozin; Low dose Sotagliflozin,once daily, before the first meal of the day
Experimental: Sotagliflozin 400 mg Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Drug: Sotagliflozin; High dose Sotagliflozin, once daily, before the first meal of the day

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in A1C at Week 24 [Baseline to Week 24]

   Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. Least square (LS) means were obtained from a mixed-effects model for repeated measures (MMRM) that included fixed, categorical effects of treatment, randomization strata of insulin delivery method (MDI, CSII), randomization strata of Week -2 A1C (<= 8.5%, >8.5%), time (study week), a treatment-by-time interaction, and baseline A1C-by-time interaction as a covariate. A negative change from baseline (a reduction of A1C value at Week 24) indicates an improvement.

Secondary Outcome Measures

1. Percentage of Participants With A1C <7.0% at Week 24 and no Episode of Severe Hypoglycemia, and no Episode of Diabetic Ketoacidosis (DKA) From Baseline to Week 24 [Baseline to Week 24]

   The composite endpoint included blood samples for the assessment of Hemoglobin A1C to determine the participants with a value <7.0% and a central blinded adjudication process to determine whether participants experienced either DKA or severe hypoglycemia. Only positively adjudicated severe hypoglycemia and diabetic ketoacidosis were included in the analysis.

2. Change From Baseline in Body Weight at Week 24 [Baseline to Week 24]

   Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model. A negative change from baseline indicates a loss in body weight from baseline to Week 24.

3. Change From Baseline in Mean Daily Bolus Insulin Dose at Week 24 [Baseline to Week 24]

   The mean bolus insulin dose in international units/day (IU/day) for Week 24 was the average over the 3 to 5 days prior to the Week 24 visit. The Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A negative change from baseline indicated a reduction in the amount of bolus insulin used and a positive change from baseline indicated an increase in the amount of bolus insulin used between baseline and Week 24.

4. Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 [Baseline to Week 24]

   The Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A negative change from baseline indicates a lower glucose level at Week 24 compared to baseline and a positive change from baseline indicates an increase in glucose level at Week 24 compared to baseline.

5. Change From Baseline in Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score at Week 24 [Baseline to Week 24]

   The DTSQ instrument contains 8 items assessing overall treatment satisfaction, treatment convenience and flexibility, satisfaction with understanding of diabetes, willingness to continue present treatment and to recommend it to others, and frequency of unacceptably high and unacceptably low blood glucose levels. 6 items (1, 4, 5, 6, 7 and 8) (excluding perceived hyperglycemia and hypoglycemia items) were scored using a 7- point scale where 0=very dissatisfied to 6= very satisfied for a total possible score of 0 (very dissatisfied) to 36 (very satisfied), where higher scores indicate higher satisfaction from treatment. Two items (Q2 and 3), which were not included, measured perceived hyperglycemia and hypoglycemia, respectively. The baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A positive change from baseline indicates improvement.

6. Change From Baseline in 2-Item Diabetes Distress Screen 2 (DDS2) Score at Week 24 [Baseline to Week 24]

   DDS2 is a 2-item diabetes distress screening instrument where participants rated the degree to which the following items caused distress: (1) feeling overwhelmed by the demands of living with diabetes, and (2) feeling that I am often failing with my diabetes regimen using a 6-point scale: where 1=no distress to 6=severe distress for a total possible score of 2 to 12. LS means were obtained from MMRM model including all available post baseline values. A negative change from baseline indicates improvement.

7. Percent Change From Baseline in Body Weight at Week 24 [Baseline to Week 24]

   Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model. A negative percent change from baseline indicates a loss in body weight from baseline to Week 24.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Participant who gave written informed consent to participate in the study in accordance with local regulations.

• Adult participants 18 years and older with a diagnosis of T1D made at least 1 year prior to informed consent.

• Participants treated with insulin or insulin analog delivered via continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI).

• Willing and were able to perform Self-monitoring of blood glucose (SMBG) and completed the study diary as required per protocol.

• At the Screening Visit, A1C was between 7.0% to 11.0%.

• Females of childbearing potential must 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	Linz		Austria	4021
2	Lexicon Investigational Site	Vienna		Austria	1010
3	Lexicon Investigational Site	Vienna		Austria	1030
4	Lexicon Investigational Site	Vienna		Austria	1130
5	Lexicon Investigational Site	Vienna		Austria	1160
6	Lexicon Investigational Site	Antwerp		Belgium	2018
7	Lexicon Investigational Site	Brussels		Belgium	1090
8	Lexicon Investigational Site	Edegem		Belgium	2650
9	Lexicon Investigational Site	Leuven		Belgium	3000
10	Lexicon Investigational Site	Sint Niklaas		Belgium	9100
11	Lexicon Investigational Site	Lovech		Bulgaria	5500
12	Lexicon Investigational Site	Plovdiv		Bulgaria	4002
13	Lexicon Investigational Site	Ruse		Bulgaria	7002
14	Lexicon Investigational Site	Smolyan		Bulgaria	4700
15	Lexicon Investigational Site	Sofia		Bulgaria	1750
16	Lexicon Investigational Site	Varna		Bulgaria	9000
17	Lexicon Investigational Site	Beziers		France	34500
18	Lexicon Investigational Site	Dijon cedex		France	21079
19	Lexicon Investigational Site	Nantes		France	44000
20	Lexicon Investigational Site	Nantes		France	44093
21	Lexicon Investigational Site	Nîmes		France	30029
22	Lexicon Investigational Site	Duesseldorf		Germany	40210
23	Lexicon Investigational Site	Hamburg		Germany	21073
24	Lexicon Investigational Site	Hamburg		Germany	22607
25	Lexicon Investigational Site	Hannover		Germany	30173
26	Lexicon Investigational Site	Mainz		Germany	55116
27	Lexicon Investigational Site	Muenster		Germany	48145
28	Lexicon Investigational Site	Neuwied		Germany	56564
29	Lexicon Investigational Site	Budapest		Hungary	1027
30	Lexicon Investigational Site	Budapest		Hungary	1042
31	Lexicon Investigational Site	Budapest		Hungary	1097
32	Lexicon Investigational Site	Budapest		Hungary	1106
33	Lexicon Investigational Site	Budapest		Hungary	1134
34	Lexicon Investigational Site	Gyula		Hungary	5700
35	Lexicon Investigational Site	Hodmezovasarhely		Hungary	6800
36	Lexicon Investigational Site	Zalaegerszeg		Hungary	8900
37	Lexicon Investigational Site	Haifa		Israel	31096
38	Lexicon Investigational Site	Holon		Israel	58100
39	Lexicon Investigational Site	Jerusalem		Israel	91120
40	Lexicon Investigational Site	Petah Tikva		Israel	49202
41	Lexicon Investigational Site	Tel Aviv		Israel	61480
42	Lexicon Investigational Site	Tel Hashomer		Israel	52621
43	Lexicon Investigational Site	Zerifin		Israel	70300
44	Lexicon Investigational Site	Catania		Italy	95123
45	Lexicon Investigational Site	Milano		Italy	20132
46	Lexicon Investigational Site	Palermo		Italy	90127
47	Lexicon Investigational Site	Perugia		Italy	06126
48	Lexicon Investigational Site	Pisa		Italy	56124
49	Lexicon Investigational Site	Roma		Italy	00128
50	Lexicon Investigational Site	Jonava		Lithuania	LT-55201
51	Lexicon Investigational Site	Kaunas		Lithuania	LT-49449
52	Lexicon Investigational Site	Kaunas		Lithuania	LT-50161
53	Lexicon Investigational Site	Dordrecht		Netherlands	3318
54	Lexicon Investigational Site	Katowice		Poland	40-060
55	Lexicon Investigational Site	Kraków		Poland	30-015
56	Lexicon Investigational Site	Lodz		Poland	90-242
57	Lexicon Investigational Site	Lublin		Poland	20-538
58	Lexicon Investigational Site	Poznan		Poland	61-655
59	Lexicon Investigational Site	Szczecin		Poland	70-506
60	Lexicon Investigational Site	Warsaw		Poland	04-736
61	Lexicon Investigational Site	Warszawa		Poland	01-518
62	Lexicon Investigational Site	Warszawa		Poland	02-507
63	Lexicon Investigational Site	Bacau		Romania	600238
64	Lexicon Investigational Site	Bucuresti		Romania	010507
65	Lexicon Investigational Site	Bucuresti		Romania	013764
66	Lexicon Investigational Site	Buzau		Romania	120203
67	Lexicon Investigational Site	Galati		Romania	800098
68	Lexicon Investigational Site	Oradea		Romania	410159
69	Lexicon Investigational Site	Sibiu		Romania	550371
70	Lexicon Investigational Site	Targu-Mures		Romania	540142
71	Lexicon Investigational Site	Bratislava		Slovakia	821 02
72	Lexicon Investigational Site	Bratislava		Slovakia	851 01
73	Lexicon Investigational Site	Kosice		Slovakia	040 01
74	Lexicon Investigational Site	Nove Zamky		Slovakia	940 01
75	Lexicon Investigational Site	Sturovo		Slovakia	943 01
76	Lexicon Investigational Site	Vrutky		Slovakia	038 61
77	Lexicon Investigational Site	Barcelona		Spain	08035
78	Lexicon Investigational Site	Barcelona		Spain	08036
79	Lexicon Investigational Site	Granada		Spain	18012
80	Lexicon Investigational Site	Malaga		Spain	29006
81	Lexicon Investigational Site	Sevilla		Spain	41003
82	Lexicon Investigational Site	Sevilla		Spain	41009
83	Lexicon Investigational Site	Sevilla		Spain	41010
84	Lexicon Investigational Site	Sevilla		Spain	41014
85	Lexicon Investigational Site	Valencia		Spain	46014
86	Lexicon Investigational Site	Härnösand		Sweden	871 82
87	Lexicon Investigational Site	Kristianstad		Sweden	291 85
88	Lexicon Investigational Site	Stockholm		Sweden	112 21
89	Lexicon Investigational Site	St. Gallen		Switzerland	9007
90	Lexicon Investigational Site	Birmingham		United Kingdom	B15 2TH
91	Lexicon Investigational Site	Blackburn		United Kingdom	BB2 3HH
92	Lexicon Investigational Site	Bristol		United Kingdom	BS10 5NB
93	Lexicon Investigational Site	Glasgow		United Kingdom	G4 0SF
94	Lexicon Investigational Site	Leeds		United Kingdom	LS2 9JT
95	Lexicon Investigational Site	Leicester		United Kingdom	LE5 4PW
96	Lexicon Investigational Site	Sheffield		United Kingdom	S5 7AU

Sponsors and Collaborators

• Lexicon Pharmaceuticals
• Sanofi

Investigators

• Study Director: Sangeeta Sawhney, M.D., Lexicon Pharmaceuticals, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Lexicon Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02421510
• Other Study ID Numbers: LX4211.1-310-T1DM; LX4211.310; 2014-005153-39
• First Posted: Apr 20, 2015
• Last Update Posted: Feb 12, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Lexicon Pharmaceuticals: High level of sugar (glucose) in the blood
• 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	Participants took part in the study at 96 investigative sites throughout 17 countries from 21 May 2015 to 23 June 2017.
Pre-assignment Detail	995 participants were screened and 782 participants with a diagnosis of Type 1 diabetes mellitus were randomized equally in 1 of 3 treatment groups: sotagliflozin 400 mg, sotagliflozin 200 mg or placebo.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
Period Title: Overall Study
STARTED	258	261	263
Completed the 24 Week Treatment Period	236	239	240
COMPLETED	225	226	227
NOT COMPLETED	33	35	36

Baseline Characteristics

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg	Total
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Total of all reporting groups
Overall Participants	258	261	263	782
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	39.7 (13.42)	42.3 (13.59)	41.7 (13.23)	41.2 (13.44)
Age, Customized (Count of Participants)
Adults (18-64 years)	244 94.6%	252 96.6%	253 96.2%	749 95.8%
From 65-84 years	14 5.4%	9 3.4%	10 3.8%	33 4.2%
Sex: Female, Male (Count of Participants)
Female	124 48.1%	122 46.7%	130 49.4%	376 48.1%
Male	134 51.9%	139 53.3%	133 50.6%	406 51.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	3 1.1%	3 1.1%	6 0.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	1 0.4%	0 0%	0 0%	1 0.1%
White	250 96.9%	252 96.6%	250 95.1%	752 96.2%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	7 2.7%	6 2.3%	10 3.8%	23 2.9%
Insulin Delivery Method (Count of Participants)
Continuous Subcutaneous Insulin Infusion (CSII)	66 25.6%	68 26.1%	67 25.5%	201 25.7%
Multiple Daily Injections (MDI)	192 74.4%	193 73.9%	196 74.5%	581 74.3%
Hemoglobin A1C (A1C) (Count of Participants)
<= 8.5%	200 77.5%	203 77.8%	204 77.6%	607 77.6%
>8.5%	58 22.5%	58 22.2%	59 22.4%	175 22.4%
Hemoglobin A1C Value at Actual Week -2 Value (Count of Participants)
<= 8.5%	202 78.3%	205 78.5%	208 79.1%	615 78.6%
>8.5%	56 21.7%	56 21.5%	55 20.9%	167 21.4%
Body Weight (Kilograms (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Kilograms (kg)]	81.08 (16.857)	81.93 (17.386)	81.97 (17.963)	81.66 (17.394)
Duration of Diabetes (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	18.1 (10.72)	18.2 (10.82)	18.9 (11.18)	18.4 (10.90)
Daily Total Insulin Dose (International units per kilogram (IU/kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [International units per kilogram (IU/kg)]	0.75 (0.295)	0.73 (0.277)	0.74 (0.267)	0.74 (0.280)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in A1C at Week 24
Description	Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. Least square (LS) means were obtained from a mixed-effects model for repeated measures (MMRM) that included fixed, categorical effects of treatment, randomization strata of insulin delivery method (MDI, CSII), randomization strata of Week -2 A1C (<= 8.5%, >8.5%), time (study week), a treatment-by-time interaction, and baseline A1C-by-time interaction as a covariate. A negative change from baseline (a reduction of A1C value at Week 24) indicates an improvement.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Analysis included participants from the modified intent to treat (mITT) population. Here, overall number of participants analyzed = participants with available data for this outcome measure.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
Measure Participants	239	239	241
Least Squares Mean (Standard Error) [Percentage of A1C]	-0.02 (0.044)	-0.39 (0.044)	-0.37 (0.043)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), 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	-0.37
	Confidence Interval	(2-Sided) 95%; -0.48 to -0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.058
	Estimation Comments	Sotagliflozin 200 mg versus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	LS means and p-values were obtained from Mixed effect Model Repeat Measurement (MMRM) model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), 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	-0.35
	Confidence Interval	(2-Sided) 95%; -0.47 to -0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sotagliflozin 400 mg versus Placebo

2. Secondary Outcome

Title	Percentage of Participants With A1C <7.0% at Week 24 and no Episode of Severe Hypoglycemia, and no Episode of Diabetic Ketoacidosis (DKA) From Baseline to Week 24
Description	The composite endpoint included blood samples for the assessment of Hemoglobin A1C to determine the participants with a value <7.0% and a central blinded adjudication process to determine whether participants experienced either DKA or severe hypoglycemia. Only positively adjudicated severe hypoglycemia and diabetic ketoacidosis were included in the analysis.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Analysis included participants from the mITT population.

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
Measure Participants	258	261	263
Number [Percentage of participants]	15.1 5.9%	31.4 12%	32.3 12.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	P-values were obtained from a Cochran-Mantel-Haenszel (CMH) test stratified by the different levels of the randomization stratification factors of insulin delivery method (MDI, CSII) and Week -2 A1C (<=8.5%, >8.5%). The 95% Confidence Limits (CL) were calculated using asymptotic Wald method. Only positively adjudicated severe hypoglycemia and diabetic ketoacidosis were included in the analysis.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Threshold for significance <= 0.05
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	16.3
	Confidence Interval	(2-Sided) 95%; 9.17 to 23.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sotagliflozin 200 mg versus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	P-values were obtained from a CMH test stratified by the different levels of the randomization stratification factors of insulin delivery method (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%). The 95% CL were calculated using asymptotic Wald method.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Threshold for significance <= 0.05
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	17.2
	Confidence Interval	(2-Sided) 95%; 10.06 to 24.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sotagliflozin 400 mg versus Placebo

3. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 24
Description	Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model. A negative change from baseline indicates a loss in body weight from baseline to Week 24.
Time Frame	Baseline to Week 24

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 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
Measure Participants	240	240	241
Least Squares Mean (Standard Error) [Kilograms (kg)]	0.11 (0.201)	-1.88 (0.200)	-2.47 (0.199)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
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	-1.98
	Confidence Interval	(2-Sided) 95%; -2.53 to -1.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.276
	Estimation Comments	Sotagliflozin 200 mg versus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-2.58
	Confidence Interval	(2-Sided) 95%; -3.12 to -2.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.276
	Estimation Comments	Sotagliflozin 400 mg versus Placebo

4. Secondary Outcome

Title	Change From Baseline in Mean Daily Bolus Insulin Dose at Week 24
Description	The mean bolus insulin dose in international units/day (IU/day) for Week 24 was the average over the 3 to 5 days prior to the Week 24 visit. The Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A negative change from baseline indicated a reduction in the amount of bolus insulin used and a positive change from baseline indicated an increase in the amount of bolus insulin used between baseline and Week 24.
Time Frame	Baseline to Week 24

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 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
Measure Participants	238	237	239
Least Squares Mean (Standard Error) [IU/day]	-1.19 (0.635)	-4.38 (0.636)	-4.78 (0.634)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and Baseline mean daily bolus insulin dose-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
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	-3.2
	Confidence Interval	(2-Sided) 95%; -4.86 to -1.53
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.847
	Estimation Comments	Sotagliflozin 200 mg versus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and Baseline mean daily bolus insulin dose-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
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	-3.59
	Confidence Interval	(2-Sided) 95%; -5.25 to -1.93
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.845
	Estimation Comments	Sotagliflozin 400 mg versus Placebo

5. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24
Description	The Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A negative change from baseline indicates a lower glucose level at Week 24 compared to baseline and a positive change from baseline indicates an increase in glucose level at Week 24 compared to baseline.
Time Frame	Baseline to Week 24

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 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
Measure Participants	239	237	239
Least Squares Mean (Standard Error) [Milligram per deciliter (mg/dL)]	8.8 (3.95)	-12.8 (3.97)	-16.9 (3.96)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline Fasting Plasma Glucose-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
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	-21.6
	Confidence Interval	(2-Sided) 95%; -32.2 to -11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.38
	Estimation Comments	Sotagliflozin 200 mg versus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline Fasting Plasma Glucose-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
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	-25.7
	Confidence Interval	(2-Sided) 95%; -36.2 to -15.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 5.37
	Estimation Comments	Sotagliflozin 400 mg versus Placebo

6. Secondary Outcome

Title	Change From Baseline in Diabetes Treatment Satisfaction Questionnaire (DTSQ) Score at Week 24
Description	The DTSQ instrument contains 8 items assessing overall treatment satisfaction, treatment convenience and flexibility, satisfaction with understanding of diabetes, willingness to continue present treatment and to recommend it to others, and frequency of unacceptably high and unacceptably low blood glucose levels. 6 items (1, 4, 5, 6, 7 and 8) (excluding perceived hyperglycemia and hypoglycemia items) were scored using a 7- point scale where 0=very dissatisfied to 6= very satisfied for a total possible score of 0 (very dissatisfied) to 36 (very satisfied), where higher scores indicate higher satisfaction from treatment. Two items (Q2 and 3), which were not included, measured perceived hyperglycemia and hypoglycemia, respectively. The baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model including all available post baseline values. A positive change from baseline indicates improvement.
Time Frame	Baseline to Week 24

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 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
Measure Participants	228	229	240
Least Squares Mean (Standard Error) [Score on a scale]	-0.1 (0.28)	1.9 (0.28)	1.6 (0.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline DTSQs total score-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
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	2
	Confidence Interval	(2-Sided) 95%; 1.3 to 2.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.37
	Estimation Comments	Sotagliflozin 200 mg versus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline DTSQs total score-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
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	1.7
	Confidence Interval	(2-Sided) 95%; 1 to 2.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.36
	Estimation Comments	Sotagliflozin 400 mg versus Placebo

7. Secondary Outcome

Title	Change From Baseline in 2-Item Diabetes Distress Screen 2 (DDS2) Score at Week 24
Description	DDS2 is a 2-item diabetes distress screening instrument where participants rated the degree to which the following items caused distress: (1) feeling overwhelmed by the demands of living with diabetes, and (2) feeling that I am often failing with my diabetes regimen using a 6-point scale: where 1=no distress to 6=severe distress for a total possible score of 2 to 12. LS means were obtained from MMRM model including all available post baseline values. A negative change from baseline indicates improvement.
Time Frame	Baseline to Week 24

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 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
Measure Participants	232	232	243
Least Squares Mean (Standard Error) [Score on a scale]	0.0 (0.12)	-0.3 (0.12)	-0.4 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 200 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<= 8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline DDS2 total score-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
Statistical Test of Hypothesis	p-Value	0.025
	Comments	Threshold for significance <= 0.05.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.6 to 0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments	Sotagliflozin 200 mg versus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Sotagliflozin 400 mg
	Comments	LS means and p-values were obtained from MMRM model with treatment, randomization strata of insulin delivery (MDI, CSII) and Week -2 A1C (<=8.5%, >8.5%), time (study week), and a treatment-by-time interaction as fixed categorical effects, and baseline DDS2 total score-by-time interaction as a covariate.
	Type of Statistical Test	Superiority
	Comments	A hierarchical testing procedure was used to control type I error and handle multiple secondary endpoint analyses. Testing was then performed sequentially in the order the endpoints were reported. The hierarchical testing sequence continued only when previous endpoint was statistically significant at 0.05 level.
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Threshold for significance <= 0.05.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -0.7 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments	Sotagliflozin 400 mg versus Placebo

8. Secondary Outcome

Title	Percent Change From Baseline in Body Weight at Week 24
Description	Baseline value was defined as the last value collected prior to the first dose of double-blind study medication. LS means were obtained from MMRM model. A negative percent change from baseline indicates a loss in body weight from baseline to Week 24.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Sotagliflozin 200 mg	Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
Measure Participants	240	240	241
Least Squares Mean (Standard Error) [Percent change]	0.10 (0.245)	-2.38 (0.245)	-2.99 (0.244)

Adverse Events

Time Frame	First dose and up to 30 days after the last dose of double-blind study treatment. Some Adverse events may have been attributed to the long-term effects of study drug; included even if the onset was >30 days after the last dose of study drug (up to 393 days).
Adverse Event Reporting Description	Safety Population consisted of all randomly assigned participants treated with at least 1 dose of study drug, analyzed according to their actual treatment received.
Arm/Group Title	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
Arm/Group Description	Two placebo-matching sotagliflozin tablets, once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.		Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.		Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, before the first meal of the day for 24 weeks followed by a 28-week extension period.
All Cause Mortality
	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/258 (0.8%)		0/261 (0%)		0/263 (0%)
Serious Adverse Events
	Placebo		Sotagliflozin 200 mg		Sotagliflozin 400 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/258 (6.6%)		26/261 (10%)		21/263 (8%)
Cardiac disorders
Acute myocardial infarction	0/258 (0%)	0	0/261 (0%)	0	2/263 (0.8%)	2
Cardiac failure	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Cardiopulmonary failure	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Coronary artery disease	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Coronary artery occlusion	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Myocardial infarction	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Endocrine disorders
Goiter	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Eye disorders
Cataract	1/258 (0.4%)	1	1/261 (0.4%)	1	0/263 (0%)	0
Angle closure glaucoma	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Vitreous haemorrhage	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Oedematous pancreatitis	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Prepyloric stenosis	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
General disorders
Impaired healing	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Pyrexia	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Hepatobiliary disorders
Cholelithiasis	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Infections and infestations
Gastroenteritis	0/258 (0%)	0	2/261 (0.8%)	2	1/263 (0.4%)	1
Pneumonia	1/258 (0.4%)	1	1/261 (0.4%)	1	0/263 (0%)	0
Cystitis	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Ecthyma	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Erysipelas	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Gastroenteritis viral	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Pilonidal cyst	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Pyoderma	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Rotavirus infection	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Injury, poisoning and procedural complications
Humerus fracture	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Ligament rupture	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Patella fracture	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Toxicity to various agents	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Ulna fracture	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Wrist fracture	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Metabolism and nutrition disorders
Diabetic ketoacidosis	0/258 (0%)	0	7/261 (2.7%)	7	12/263 (4.6%)	12
Hypoglycaemia	0/258 (0%)	0	2/261 (0.8%)	2	1/263 (0.4%)	1
Diabetes mellitus inadequate control	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Ketosis	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Musculoskeletal and connective tissue disorders
Musculoskeletal stiffness	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Rhabdomyolysis	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma	1/258 (0.4%)	1	1/261 (0.4%)	1	0/263 (0%)	0
Breast cancer metastatic	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Chronic myeloid leukaemia	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Clear cell renal cell carcinoma	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Invasive breast carcinoma	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Lung neoplasm malignant	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Nervous system disorders
Hypoglycaemic unconsciousness	3/258 (1.2%)	3	2/261 (0.8%)	2	1/263 (0.4%)	1
Hypoglycaemic seizure	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Ischaemic stroke	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Sciatica	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Syncope	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Transient ischaemic attack	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Vascular headache	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Renal and urinary disorders
Cystitis noninfective	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Reproductive system and breast disorders
Ovarian cyst	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	0
Vaginal haemorrhage	0/258 (0%)	0	0/261 (0%)	0	1/263 (0.4%)	1
Skin and subcutaneous tissue disorders
Dermatitis atopic	1/258 (0.4%)	1	0/261 (0%)	0	0/263 (0%)	0
Diabetic foot	0/258 (0%)	0	1/261 (0.4%)	1	0/263 (0%)	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	46/258 (17.8%)		52/261 (19.9%)		64/263 (24.3%)
Gastrointestinal disorders
Diarrhoea	10/258 (3.9%)	13	12/261 (4.6%)	18	20/263 (7.6%)	29
Respiratory, thoracic and mediastinal disorders
Viral upper respiratory tract infection	40/258 (15.5%)	58	44/261 (16.9%)	60	49/263 (18.6%)	70

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.