Efficacy, Safety, and Tolerability Study of Sotagliflozin... | NCT02384941

NCT02384941

Status Module

Sponsor/Collaborators Module

Name	Class
Sanofi	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Placebo	Placebo Comparator	Two placebo-matching sotagliflozin tables, orally for 24 weeks followed by a 28 week extension period.	Drug: Placebo
Sotagliflozin 200 milligrams (mg)	Experimental	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), orally, for 24 weeks followed by a 28 week extension period.	Drug: Placebo Drug: Sotagliflozin
Sotagliflozin 400 mg	Experimental	Sotagliflozin 400 mg (two 200 mg tablets), orally, for 24 weeks followed by a 28 week extension period.	Drug: Sotagliflozin

Name	Type	Description	Arm Group Labels	Other Names
Placebo	Drug	Placebo once daily, before first meal of the day.	Placebo Sotagliflozin 200 milligrams (mg)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in A1C at 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 lower A1C value at Week 24) indicates an improvement.	Baseline to Week 24

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With A1C <7.0% (at Week 24) and No Episode of Severe Hypoglycemia and No Episode of Diabetic Ketoacidosis (DKA) Upto Week 24	Blood samples were collected for the assessment of Hemoglobin A1C to determine the participants with A1C value <7.0%. A central blinded adjudication process determined whether participants experienced either DKA or Severe Hypoglycemia. Only positively adjudicated severe hypoglycemia and diabetic ketoacidosis were included in the analysis.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Sangeeta Sawhney, M.D.	Lexicon Pharmaceuticals, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Lexicon Investigational Site		Birmingham	Alabama	35294	United States
Lexicon Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
32928957	Derived	Peters AL, McGuire DK, Danne T, Kushner JA, Rodbard HW, Dhatariya K, Sawhney S, Banks P, Jiang W, Davies MJ, Lapuerta P. Diabetic Ketoacidosis and Related Events With Sotagliflozin Added to Insulin in Adults With Type 1 Diabetes: A Pooled Analysis of the inTandem 1 and 2 Studies. Diabetes Care. 2020 Nov;43(11):2713-2720. doi: 10.2337/dc20-0924. Epub 2020 Sep 14.
32721228

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.
FG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Modified intent to treat (mITT) analysis set included all randomly assigned participants who have taken at least 1 dose of study drug.

Arm/Group Information

ID	Title	Description
BG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.
BG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.
BG002	Sotagliflozin 400 mg	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 24 weeks followed by a 28 week extension period.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00045.2± 12.72 BG00146.6± 13.48 BG00246.4± 13.12 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000131 BG001137 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Hemoglobin A1C (A1C)

Mean

Standard Deviation

percentage of A1C

Title

Denominators

Categories

Title	Measurements
	BG0007.54± 0.712 BG0017.61± 0.735 BG002

Body Weight

Mean

Standard Deviation

kilograms (kg)

Title

Denominators

Categories

Title	Measurements
	BG00087.30± 17.709 BG00186.96± 18.539 BG002

Baseline Daily Total Insulin Dose

Mean

Standard Deviation

International Unit per kilogram (IU/kg)

Title

Denominators

Categories

Title	Measurements
	BG0000.74± 0.357 BG0010.72± 0.386 BG002

Body Mass Index (BMI)

Mean

Standard Deviation

kilograms/square meter (kg/m^2)

Title

Denominators

Categories

Title	Measurements
	BG00029.55± 5.188 BG00129.81± 5.686 BG002

Duration of Diabetes

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00024.2± 12.38 BG00125.0± 13.15 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in A1C at 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 lower A1C value at Week 24) indicates an improvement.

Modified intent to treat (mITT) analysis set included all randomly assigned participants who have taken at least 1 dose of study drug. Here, "Overall Number of Participants" Analyzed signified participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

percentage of A1C

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.
OG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.
OG002	Sotagliflozin 400 mg	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 24 weeks followed by a 28 week extension period.

Units	Counts
Participants	OG000246 OG001245 OG002242

Title

Denominators

Categories

Title	Measurements
	OG000-0.07± 0.036 OG001-0.43± 0.036 OG002-0.48± 0.036

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		MMRM		<0.001	Threshold for significance < 0.05.	Least squares mean difference	-0.36	Standard Error of the Mean	0.047	2-Sided								Superiority
OG000 OG002		MMRM

Secondary

Percentage of Participants With A1C <7.0% (at Week 24) and No Episode of Severe Hypoglycemia and No Episode of Diabetic Ketoacidosis (DKA) Upto Week 24

Blood samples were collected for the assessment of Hemoglobin A1C to determine the participants with A1C value <7.0%. A central blinded adjudication process determined whether participants experienced either DKA or Severe Hypoglycemia. Only positively adjudicated severe hypoglycemia and diabetic ketoacidosis were included in the analysis.

Analysis performed on mITT analysis set.

Posted

Number

percentage of participants

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.
OG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.
OG002	Sotagliflozin 400 mg	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 24 weeks followed by a 28 week extension period.

Secondary

Absolute Change From Baseline in Body Weight at 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.

Analysis performed on mITT analysis set. Here, "Overall Number of Participants Analyzed" signified participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

kilograms (kg)

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.
OG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.
OG002	Sotagliflozin 400 mg	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 24 weeks followed by a 28 week extension period.

Secondary

Change From Baseline in Mean Daily Bolus Insulin Dose at Week 24

The mean bolus insulin dose in international units per 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 between Baseline and Week 24.

Analysis performed on mITT analysis set. Here, "Overall Number of Participants Analyzed" signified participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

IU/day

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.
OG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.
OG002	Sotagliflozin 400 mg	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 24 weeks followed by a 28 week extension period.

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG) at 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 at Week 24 compared to baseline.

Analysis performed on mITT analysis set. Here, "Overall Number of Participants Analyzed" signified participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

millimole per liter (mmol/L)

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Two placebo-matching sotagliflozin tables, once daily, orally for 24 weeks followed by a 28 week extension period.
OG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.
OG002	Sotagliflozin 400 mg	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 24 weeks followed by a 28 week extension period.

Secondary

Change From Baseline in Diabetes Total Treatment Satisfaction Scores as Measured by Total Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Scores at Week 24

DTSQs is a diabetes-specific measure used to evaluate overall treatment satisfaction and perception of hyperglycemia and hypoglycemia events. It consists of 8 items and the response categories for all items were on a 7-point likert scale.The DTSQs response options ranged from 0 (very dissatisfied) to 6 (very satisfied). Responses to item 1, 4, 5, 6, 7 and 8 were summarized to determine the total treatment satisfaction score which ranged from 0 (very dissatisfied) to 36 (very satisfied), with a higher score corresponding to higher satisfaction . LS means were obtained from MMRM model including all available post baseline values. A positive change from baseline indicates improvement.

Analysis performed on mITT analysis set. Here, "Overall Number of Participants Analyzed" signified participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.
OG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.

Secondary

Change From Baseline in Diabetes Distress Scores as Measured by 2-item Diabetes Distress Screening Scale (DDS2) Scores at Week 24

The DDS2 is a 2-item diabetes distress screening instrument where respondents rated, on a 6-point scale, 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 (not a problem) to 12 (very serious problem), with higher score corresponding to higher distress. LS means were obtained from MMRM model including all available post baseline values. A negative change from baseline indicates improvement.

Analysis performed on mITT analysis set. Here, "Overall Number of Participants Analyzed" signified participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.
OG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.
OG002

Secondary

Percent Change From Baseline in Body Weight at 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.

Analysis performed on mITT analysis set. Here, "Overall Number of Participants Analyzed" signified participants with available data for this outcome measure.

Posted

Least Squares Mean

Standard Error

percent change

Baseline to Week 24

ID	Title	Description
OG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.
OG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.
OG002	Sotagliflozin 400 mg	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 24 weeks followed by a 28 week extension period.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Two placebo-matching sotagliflozin tablets, once daily, orally for 24 weeks followed by a 28 week extension period.	1	268	20	268	129	268
EG001	Sotagliflozin 200 mg	Sotagliflozin 200 mg (one 200 mg tablet and one placebo tablet), once daily, orally, for 24 weeks followed by a 28 week extension period.	0	263	27	263	132	263
EG002	Sotagliflozin 400 mg	Sotagliflozin 400 mg (two 200 mg tablets), once daily, orally, for 24 weeks followed by a 28 week extension period.	0	262	29	262	130	262

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA(20.0)	Systematic Assessment	EG0002 events2 affected268 at risk EG0012 events2 affected263 at risk EG0020 events0 affected262 at risk
Angina unstable	Cardiac disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Aortic valve incompetence	Cardiac disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Atrial fibrillation	Cardiac disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Coronary artery disease	Cardiac disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Myocardial infarction	Cardiac disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Constipation	Gastrointestinal disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Chest pain	General disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Non-cardiac chest pain	General disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Appendicitis	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0021 events1 affected262 at risk
Cellulitis	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Diverticulitis	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Endocarditis	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Gastroenteritis viral	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Meningitis viral	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Pneumonia	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0021 events1 affected262 at risk
Postoperative wound infection	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Sepsis	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Limb injury	Injury, poisoning and procedural complications	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Hepatic enzyme increased	Investigations	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Acetonaemia	Metabolism and nutrition disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA(20.0)	Systematic Assessment	EG0003 events3 affected268 at risk EG00113 events12 affected263 at risk EG00214 events14 affected262 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA(20.0)	Systematic Assessment	EG0007 events5 affected268 at risk EG0015 events3 affected263 at risk EG0024 events4 affected262 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Intraductal proliferative breast lesion	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Parathyroid tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Hypoglycaemic seizure	Nervous system disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Hypoglycaemic unconsciousness	Nervous system disorders	MedDRA(20.0)	Systematic Assessment	EG0003 events1 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Intracranial aneurysm	Nervous system disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Ischaemic stroke	Nervous system disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk
Mental status changes	Psychiatric disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0011 events1 affected263 at risk EG0020 events0 affected262 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Foot amputation	Surgical and medical procedures	MedDRA(20.0)	Systematic Assessment	EG0000 events0 affected268 at risk EG0010 events0 affected263 at risk EG0021 events1 affected262 at risk
Orthostatic hypotension	Vascular disorders	MedDRA(20.0)	Systematic Assessment	EG0001 events1 affected268 at risk EG0010 events0 affected263 at risk EG0020 events0 affected262 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Blood ketone body increased	Investigations	MedDRA(20.0)	Systematic Assessment	EG0002 events2 affected268 at risk EG00120 events10 affected263 at risk EG00219 events14 affected262 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA(20.0)	Systematic Assessment	EG00013 events10 affected268 at risk EG0016 events6 affected263 at risk EG00218 events18 affected262 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA(20.0)	Systematic Assessment	EG00021 events19 affected268 at risk EG00126 events22 affected263 at risk EG00241 events29 affected262 at risk
Nausea	Gastrointestinal disorders	MedDRA(20.0)	Systematic Assessment	EG00021 events18 affected268 at risk EG00123 events17 affected263 at risk EG00224 events18 affected262 at risk
Sinusitis	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG00016 events13 affected268 at risk EG00120 events14 affected263 at risk EG00210 events9 affected262 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG00052 events43 affected268 at risk EG00138 events33 affected263 at risk EG00246 events33 affected262 at risk
Urinary tract infection	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG00023 events18 affected268 at risk EG00134 events25 affected263 at risk EG00214 events9 affected262 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG00033 events29 affected268 at risk EG00141 events34 affected263 at risk EG00229 events24 affected262 at risk
Vulvovaginal mycotic infection	Infections and infestations	MedDRA(20.0)	Systematic Assessment	EG0008 events6 affected268 at risk EG00118 events13 affected263 at risk EG00223 events21 affected262 at risk

ID	Term
D003922	Diabetes Mellitus, Type 1

Ancestor Terms

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases
D001327	Autoimmune Diseases
D007154	Immune System Diseases

ID	Term
C575681	(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol

Units	Counts
Participants	OG000268 OG001263 OG002262

Units	Counts
Participants	OG000245 OG001245 OG002242