Non-inferiority Study to Compare the Efficacy and Safety... | NCT02227862

Status Module

Name	Class
Mylan GmbH	INDUSTRY

Oversight Module

Description 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
Mylan's Insulin Glargine	Experimental	Receive Mylan's Insulin Glargine plus insulin lispro.	Drug: Mylan's insulin glargine
Lantus®	Active Comparator	Receive Lantus® plus insulin lispro	Drug: Lantus®

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Mylan's insulin glargine	Drug	All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Outcomes Module

Measure	Description	Time Frame
Change in HbA1c From Baseline to 24 Weeks		24 weeks

Secondary Outcomes

Measure	Description	Time Frame
Summary of Actual and Change From Baseline in HbA1c		24 and 52 weeks
Change From Baseline in FPG Over Time		24 and 52 weeks
Change From Baseline in 8-point SMBG Profile Over Time

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Thomas Blevins, MD	Texas Diabetes & Endocrinology	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Mylan Investigational Site		Bell Gardens	California	90201	United States
Mylan Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
34174848	Derived	Sun B, Sengupta N, Rao A, Donnelly C, Waichale V, Roy AS, Ramaswamy S, Pathak D, Bowsher RR, Raiter Y, Aubonnet P, Barve A. Similar immunogenicity profiles between the proposed biosimilar MYL-1501D and reference insulin glargine in patients with diabetes mellitus: the phase 3 INSTRIDE 1 and INSTRIDE 2 studies. BMC Endocr Disord. 2021 Jun 26;21(1):129. doi: 10.1186/s12902-021-00797-4.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
BG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
BG002	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, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00042± 12.03 BG00142.2± 11.97 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000116 BG001106 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Asian

Title	Measurements
	BG0002 BG0012 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Europe

Title	Measurements
	BG000145 BG001145 BG002

Insulin History

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Yes	BG000280 BG001277 BG002

Dosing Time

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Morning	BG00038 BG00140 BG002

Body Mass Index (BMI)

Mean

Standard Deviation

kg/m2

Title

Denominators

Categories

Title	Measurements
	BG00026.435± 3.7058 BG00126.636± 4.2022 BG002

Duration of Diabetes

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00018.685± 11.7771 BG00119.697± 11.2868 BG002

Baseline fasting plasma glucose

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000167.4± 68.43 BG001163.9± 61.61 BG002

Baseline HbA1c

Mean

Standard Deviation

percent

Title

Denominators

Categories

Title	Measurements
	BG0007.37± 0.869 BG0017.39± 0.843 BG002

Baseline fasting C-peptide

Mean

Standard Deviation

mmol/L

Title

Denominators

Categories

Title	Measurements
	BG0000.298± 0.2291 BG0010.291± 0.2508 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 in HbA1c From Baseline to 24 Weeks

Posted

Least Squares Mean

Standard Error

percent

24 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Units	Counts
Participants	OG000280 OG001277

Title

Denominators

Categories

Title	Measurements
	OG0000.14± 0.054 OG0010.11± 0.054

Secondary

Summary of Actual and Change From Baseline in HbA1c

Posted

Mean

Standard Deviation

percent

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Change From Baseline in FPG Over Time

Posted

Mean

Standard Deviation

mmol/L

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Change From Baseline in 8-point SMBG Profile Over Time

Posted

Mean

Standard Deviation

mmol/L

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Change in Total Daily Insulin Dose Per Unit Body Weight From Baseline Over Time

Posted

Mean

Standard Deviation

U/Kg

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Rate of Hypoglycemic Events Per 30 Days Over Time

Posted

Mean

Standard Deviation

Episodes/30 Days

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Hypoglycemia Occurrence

Posted

Number

Number of patients

52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Units

Secondary

Occurrence of Local and Systematic Reactions

Posted

Number

Number of patients

52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Change in Total Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time

Posted

Mean

Standard Deviation

%SB

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Change in Total Insulin Antibody Percent Binding for Lantus Assay Over Time

Posted

Mean

Standard Deviation

%SB

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Change in Cross-reactive Insulin Antibody Percent Binding for Mylan's Insulin Glargine Assay Over Time

Posted

Mean

Standard Deviation

%SB

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Change in Cross-reactive Insulin Antibody Percent Binding for Lantus Assay Over Time

Posted

Mean

Standard Deviation

%SB

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

Secondary

Proportion of Patients With HbA1c < 7%

Posted

Count of Participants

Participants

24 and 52 weeks

ID	Title	Description
OG000	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.
OG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.

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	Mylan's Insulin Glargine	Receive Mylan's Insulin Glargine plus insulin lispro. Mylan's insulin glargine: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period, and will continue on this for the complete trial. During the 6 week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	2	280	18	280	225	225
EG001	Lantus®	Receive Lantus® plus insulin lispro Lantus®: All patients will be shifted from their current mealtime insulin to insulin lispro at the start of the run-in period; and will continue on this for the complete trial. During the 6week run-in period the doses of Lantus® and insulin lispro will be titrated (if required) to ensure diabetes control. After the run-in period, patients will be randomized to receive either Mylan's insulin glargine (in place of Lantus®), or to continue on Lantus®. During the period from 12 to 24 weeks dose titration will be kept to a minimum.	1	278	22	278	239	239

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Malignant oligodendroglioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Death	General disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Psychotic disorder	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Postoperative respiratory distress	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Scapula fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Coronary artery disease	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0011 events1 affected278 at risk
Myocardial infarction	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Epilepsy	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Generalized tonic-clonic seizure	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0012 events2 affected278 at risk
Hypoglycaemic seizure	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Retinal artery occlusion	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected280 at risk EG0010 events0 affected278 at risk
Glomerulonephritis minimal lesion	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Osteochondrosis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Goitre	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0012 events2 affected278 at risk
Hypothyroidism	Endocrine disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0007 events7 affected280 at risk EG00110 events10 affected278 at risk
Cellulitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Diverticulitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Haematoma infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Pharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Pneumonia	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Urosepsis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected280 at risk EG0010 events0 affected278 at risk
Viral rash	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk
Depression	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected280 at risk EG0011 events1 affected278 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Hypertension	Vascular disorders	MedDRA 18.1	Systematic Assessment	EG0009 events9 affected225 at risk EG0016 events6 affected239 at risk
Seasonal allergy	Immune system disorders	MedDRA 18.1	Systematic Assessment	EG0004 events2 affected225 at risk EG0013 events3 affected239 at risk
Pyrexia	General disorders	MedDRA 18.1	Systematic Assessment	EG0006 events5 affected225 at risk EG0014 events4 affected239 at risk
Oedema peripheral	General disorders	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected225 at risk EG0013 events3 affected239 at risk
Fatigue	General disorders	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected225 at risk EG0012 events2 affected239 at risk
Depression	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected225 at risk EG0013 events3 affected239 at risk
Anxiety	Psychiatric disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0011 events1 affected239 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0012 events2 affected239 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected225 at risk EG0014 events4 affected239 at risk
Blood pressure increased	Investigations	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected225 at risk EG0013 events3 affected239 at risk
Tachycardia	Cardiac disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected225 at risk EG0013 events3 affected239 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0006 events6 affected225 at risk EG0015 events5 affected239 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0006 events6 affected225 at risk EG0013 events3 affected239 at risk
Sinus congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected225 at risk EG0014 events4 affected239 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Systematic Assessment	EG0006 events5 affected225 at risk EG0010 events0 affected239 at risk
Headache	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0005 events5 affected225 at risk EG00120 events14 affected239 at risk
Carpal tunnel syndrome	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0005 events4 affected225 at risk EG0010 events0 affected239 at risk
Diabetic neuropathy	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected225 at risk EG0013 events3 affected239 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0010 events0 affected239 at risk
Diabetic retinopathy	Eye disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected225 at risk EG0015 events5 affected239 at risk
Nausea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00010 events10 affected225 at risk EG0018 events6 affected239 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG00012 events11 affected225 at risk EG0014 events4 affected239 at risk
Toothache	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0007 events4 affected225 at risk EG0015 events5 affected239 at risk
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Systematic Assessment	EG0007 events6 affected225 at risk EG0013 events2 affected239 at risk
Microalbuminuria	Renal and urinary disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0010 events0 affected239 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected225 at risk EG0014 events4 affected239 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG00013 events9 affected225 at risk EG0014 events2 affected239 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0005 events5 affected225 at risk EG0017 events6 affected239 at risk
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0004 events4 affected225 at risk EG0010 events0 affected239 at risk
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0010 events0 affected239 at risk
Trigger finger	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0000 events0 affected225 at risk EG0013 events3 affected239 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003,045 events154 affected225 at risk EG0013,184 events170 affected239 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0016 events5 affected239 at risk
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected225 at risk EG0013 events3 affected239 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0010 events0 affected239 at risk
Nasopharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00037 events25 affected225 at risk EG00158 events39 affected239 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00038 events27 affected225 at risk EG00144 events33 affected239 at risk
Influenza	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00012 events12 affected225 at risk EG00114 events12 affected239 at risk
Urinary tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00013 events9 affected225 at risk EG00111 events10 affected239 at risk
Bronchitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0009 events9 affected225 at risk EG0018 events8 affected239 at risk
Gastroenteritis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00010 events10 affected225 at risk EG0016 events6 affected239 at risk
Sinusitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG00010 events8 affected225 at risk EG0018 events8 affected239 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0006 events6 affected225 at risk EG0017 events7 affected239 at risk
Viral infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0005 events5 affected225 at risk EG0016 events6 affected239 at risk
Pharyngitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0005 events5 affected225 at risk EG0012 events2 affected239 at risk
Fungal infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0014 events3 affected239 at risk
Pharyngitis streptococcal	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0006 events4 affected225 at risk EG0012 events2 affected239 at risk
Rhinitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected225 at risk EG0015 events5 affected239 at risk
Respiratory tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0002 events2 affected225 at risk EG0013 events3 affected239 at risk
Onychomycosis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected225 at risk EG0013 events3 affected239 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Systematic Assessment	EG0005 events5 affected225 at risk EG0013 events3 affected239 at risk
Respiratory tract infection viral	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected225 at risk EG0014 events3 affected239 at risk
Tonsilitis	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0011 events1 affected239 at risk
Vulvovaginal mycotic infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0001 events1 affected225 at risk EG0013 events3 affected239 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Systematic Assessment	EG0003 events3 affected225 at risk EG0010 events0 affected239 at risk

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
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins