An Administration Method Study of Human Regular U-500 Ins... | NCT02561078

ID	Type	Description	Link
B5K-MC-IBHD	Other Identifier	Eli Lilly and Company

Name	Class
Insulet Corporation	INDUSTRY

Label	Type	Description	Intervention Names
Human regular U-500 insulin administered by CSII	Experimental	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.	Drug: Human regular U-500 insulin (CSII)
Human regular U-500 insulin administered by MDI	Active Comparator	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.	Drug: Human regular U-500 insulin (MDI)

Name	Type	Description	Arm Group Labels	Other Names
Human regular U-500 insulin (CSII)	Drug	Administered SC	Human regular U-500 insulin administered by CSII

Measure	Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.	Baseline, 26 Weeks

Measure	Description	Time Frame
Change From Baseline in Fasting Plasma Glucose (FPG)	Fasting plasma glucose (FPG) is a test to determine how much glucose (sugar) is in a plasma sample after an overnight fast. Least Squares (LS) means was determined by MMRM methodology with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosed with type 2 diabetes mellitus (T2DM).
Current TDD >200 but ≤600 units of non U-500R insulin (MDI or CSII) and/or U-500R by MDI with syringe and vial for ≥3 months at entry.
- If TDD of U-500R and other insulins are combined, then insulin other than U-500R not to exceed 25% of TDD.
HbA1c ≥7.5% and ≤12.0%.
Body mass index ≥25 but ≤50 kilograms per meter squared.
Have a history of stable body weight.
Concomitant antihyperglycemic agent (AHA) therapy may include metformin (MET), dipeptidyl peptidase-4 inhibitors and/or pioglitazone.
- Approximately 64 to 96 subjects using glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors will be enrolled in Study Group B.

Exclusion Criteria:

Diagnosed with type 1 diabetes mellitus (T1DM) or other types of diabetes apart from T2DM.
Have obvious clinical or radiographic signs or symptoms of liver disease (except nonalcoholic fatty liver disease), cirrhosis, acute or chronic hepatitis, or alanine aminotransferase (ALT/SGPT) and/or aspartate aminotransferase (AST/SGOT) levels ≥2.5X upper limit of normal (ULN), alkaline phosphatase ≥2X ULN or total bilirubin ≥2X ULN.
Have chronic kidney disease Stage 4 and higher or history of renal transplantation.
Have history of more than 1 episode of severe hypoglycemia within the 6 months prior to screening.
Have received U-500R insulin by CSII in the 3 months prior to screening.
Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia.
Are taking chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy.
Have an irregular sleep/wake cycle.
Have used any weight loss drugs in the 3 months prior to screening.
Have a history of bariatric surgery including Roux-en-Y gastric bypass surgery, gastric banding, and/or gastric sleeve.
Have a history of an active or untreated malignancy, or in remission from a clinically significant malignancy during the last 5 years before screening.
Significant hearing loss and/or vision impairment deemed by the investigator to interfere with the safe use of OmniPod U-500 system.
Have cardiac disease with functional status that is New York Heart Association (NYHA) Class III or IV per New York Heart Association Cardiac Disease Functional Classification or have congestive heart failure requiring pharmacologic treatment.
Are women breastfeeding or pregnant, or intend to become pregnant during the course of the study; are men who intend to impregnate their partners; or are sexually active of procreation potential not actively practicing birth control by a method determined by the investigator to be medically acceptable. Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.

Name	Affiliation	Role
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Internal Medicine Center LLC		Mobile	Alabama	36608	United States
John Muir Physician Network Clinical Research Center

Label	URL
Click here for more information about this study: An Administration Method Study of Human Regular U-500 Insulin (LY041001) in Participants With Type 2 Diabetes Mellitus	View source

ID	Title	Description
FG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by continuous subcutaneous insulin infusion (CSII) and titrated based on blood glucose readings for 26 weeks with a 2-week multiple daily injections (MDI) lead-in.
FG001	Human Regular U-500 Insulin Administered by MDI

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol: Study Protocol	Jun 11, 2015

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 Hemoglobin A1c (HbA1c)

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time.

Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.

All randomized participants who received at least 1 dose of study drug with baseline and post-baseline HbA1c measure.

Posted

Least Squares Mean

Standard Error

Percentage of HbA1c

Baseline, 26 Weeks

ID	Title	Description
OG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
OG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.

Units	Counts
Participants	OG000171 OG001179

Title

Denominators

Categories

Title	Measurements
	OG000-1.27± 0.072 OG001-0.85± 0.070

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		Mixed Models Analysis		<0.001		Mean Difference (Net)	-0.42			2-Sided	95	-0.62	-0.22					Non-Inferiority	The test for the primary objective of noninferiority was performed at the 0.05 significance level using the LS Mean estimate of the difference in change in HbA1c between the 2 treatments at Week 26. Noninferiority was established if the upper limit of a 2-sided 95% confidence interval (CI) for the difference (U 500R CSII minus U 500R MDI) was below the noninferiority margin (NIM) of 0.4%.

Secondary

Change From Baseline in Fasting Plasma Glucose (FPG)

Fasting plasma glucose (FPG) is a test to determine how much glucose (sugar) is in a plasma sample after an overnight fast. Least Squares (LS) means was determined by MMRM methodology with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.

All randomized participants who received at least 1 dose of study drug with baseline and post-baseline fasting plasma glucose measure.

Posted

Least Squares Mean

Standard Error

milligrams per deciliter (mg/dL)

Baseline, 26 Weeks

ID	Title	Description
OG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
OG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.

Units	Counts
Participants

Secondary

Percentage of Participants With HbA1c <7.0%

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Longitudinal logistic regression was used to model the likelihood of having hbA1c<7.0% at Week 26 with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.

All randomized participants who received at least 1 dose of study drug with baseline and post-baseline HbA1c measure.

Posted

Number

Percentage of participants

26 Weeks

ID	Title	Description
OG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
OG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.

Units	Counts
Participants

Secondary

Percentage of Participants With HbA1c <7.5%

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Longitudinal logistic regression was used to model the likelihood of having hbA1c<7.5% at Week 26 with baseline of response, glucagon-like peptide-1 (GLP-1) or sodium-glucose cotransporter 2 (SGLT2) use, U-500R at entry, treatment, time and treatment by time interaction.

All randomized participants who received at least 1 dose of study drug with baseline and post-baseline HbA1c measure.

Posted

Number

Percentage of Participants

26 Weeks

ID	Title	Description
OG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
OG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.

Units	Counts
Participants

Secondary

Change From Baseline in 7-point Self-Monitored Blood Glucose (SMBG) Values

Seven-point SMBG are completed at the following timepoints: Before Morning Meal, 2 Hours After Morning Meal, Before Mid-Day Meal, 2 Hours After Mid-Day Meal, Before Evening Meal, Bed Time and 03:00 AM hours. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline of response, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, treatment, time and treatment by time interaction.

All randomized participants who received at least 1 dose of study drug with baseline and post-baseline SMBG measure.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, 26 Weeks

ID	Title	Description
OG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
OG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.

Units	Counts

Secondary

Change From Baseline in Total Daily Dose (TDD)

Baseline TDD was defined as the last prestudy insulin TDD prior to randomization to receiving the first dose of U-500 insulin post randomization. Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline of response, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, treatment, time and treatment by time interaction.

All randomized participants who received at least 1 dose of study drug with baseline and post-baseline TDD measure.

Posted

Least Squares Mean

Standard Error

units/day

Baseline, 26 Weeks

ID	Title	Description
OG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
OG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.

Units	Counts
Participants

Secondary

Percentage of Participants With Hypoglycemic Episodes (Documented Hypoglycemia With Blood Glucose <= 70 mg/dL)

The percentage of participants with hypoglycemic episodes (documented hypoglycemia) was calculated by dividing the number of participants with at least 1 hypoglycemic episode (documented hypoglycemia) over the 26-week treatment period by the total number of participants analyzed, multiplied by 100%. Logistic regression was used to estimate the odds ratio between the two treatments of at least 1 hypoglycemic episode (documented hypoglycemia) over 26 week treatment period adjusted for baseline documented hypoglycemia rate, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, treatment, time and treatment by time interaction.

All randomized participants who received at least 1 dose of study drug with baseline and post-baseline documented hypoglycemia.

Posted

Number

Percentage of Participants

26 Weeks

ID	Title	Description
OG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
OG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.

Secondary

Rate of Hypoglycemic Episodes (Documented Hypoglycemia With Blood Glucose <= 70 mg/dL)

Documented Hypoglycemic episodes with blood glucose<=70mg/dL was used in this outcome measure. Hypoglycemia rate (documented hypoglycemia) per 30 days was summarized at each visit by treatment group. The rate of hypoglycemia (documented hypoglycemia) was analyzed using a generalized estimation equations model with a negative binomial distribution and a Log link. LS mean was determined by MMRM methodology with baseline documented hypoglycemia rate, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, with log of exposure in days divided by 30 as the offset, treatment, visit, and visit by treatment interaction.

All randomized participants who received at least 1 dose of study drug with baseline and post-baseline documented hypoglycemia.

Posted

Least Squares Mean

Standard Error

Episodes/participant/30 days

Baseline to 26 Weeks

ID	Title	Description
OG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
OG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.

Secondary

Change From Baseline in Body Weight

Least Squares (LS) means was determined by mixed model repeated measures (MMRM) methodology with baseline of response, GLP-1 or SGLT2 use, U-500R at entry, baseline HbA1C group, treatment, treatment by time interaction.

All randomized participants who received at least 1 dose of study drug with baseline and post-baseline body weight.

Posted

Least Squares Mean

Standard Error

Kilograms (kg)

Baseline, 26 Weeks

ID	Title	Description
OG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
OG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute coronary syndrome	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Angina pectoris	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0002 events1 affected209 at risk EG0010 events0 affected211 at risk
Angina unstable	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Atrial flutter	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0011 events1 affected211 at risk
Cardiac arrest	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected209 at risk EG0010 events0 affected211 at risk
Cor pulmonale	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Coronary artery disease	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0011 events1 affected211 at risk
Left ventricular failure	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Myocardial infarction	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Ventricular tachycardia	Cardiac disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Diabetic retinopathy	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Retinal detachment	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Vitreous haemorrhage	Eye disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Colitis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Asthenia	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0011 events1 affected211 at risk
Non-cardiac chest pain	General disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0012 events2 affected211 at risk
Bronchitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Cellulitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Infected skin ulcer	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Influenza	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Osteomyelitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Perirectal abscess	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Pneumonia	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0004 events4 affected209 at risk EG0012 events2 affected211 at risk
Pyelonephritis acute	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Sepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0003 events3 affected209 at risk EG0010 events0 affected211 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Urosepsis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG00012 events10 affected209 at risk EG0015 events5 affected211 at risk
Obesity	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Compartment syndrome	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0002 events2 affected209 at risk EG0010 events0 affected211 at risk
Encephalopathy	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Hypoglycaemic seizure	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Loss of consciousness	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Lumbar radiculopathy	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Moyamoya disease	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Peroneal nerve palsy	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Syncope	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Device malfunction	Product Issues	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Depression	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0011 events1 affected211 at risk
Depression suicidal	Psychiatric disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0013 events3 affected211 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Ureterolithiasis	Renal and urinary disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0013 events3 affected211 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected211 at risk
Diabetic foot	Skin and subcutaneous tissue disorders	MedDRA 20.0	Systematic Assessment	EG0001 events1 affected209 at risk EG0010 events0 affected211 at risk

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

ID	Title	Description
BG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.
BG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Human Regular U-500 Insulin Administered by CSII	Human regular U-500 insulin administered by CSII and titrated based on blood glucose readings for 26 weeks with a 2-week MDI lead-in.	2	209	34	209	85	209
EG001	Human Regular U-500 Insulin Administered by MDI	Human regular U-500 insulin administered subcutaneously (SC) by MDI three times a day and titrated based on blood glucose readings for 26 weeks.	1	211	23	211	84	211

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG00018 events14 affected209 at risk EG00122 events17 affected211 at risk
Nausea	Gastrointestinal disorders	MedDRA 20.0	Systematic Assessment	EG0009 events9 affected209 at risk EG00120 events17 affected211 at risk
Sinusitis	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG00010 events10 affected209 at risk EG00115 events13 affected211 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG00017 events17 affected209 at risk EG00119 events18 affected211 at risk
Urinary tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG0004 events3 affected209 at risk EG00111 events11 affected211 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA 20.0	Systematic Assessment	EG00012 events11 affected209 at risk EG00121 events18 affected211 at risk
Weight increased	Investigations	MedDRA 20.0	Systematic Assessment	EG00014 events14 affected209 at risk EG00113 events13 affected211 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 20.0	Systematic Assessment	EG00017 events11 affected209 at risk EG0010 events0 affected211 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 20.0	Systematic Assessment	EG00011 events11 affected209 at risk EG00116 events13 affected211 at risk
Headache	Nervous system disorders	MedDRA 20.0	Systematic Assessment	EG00011 events9 affected209 at risk EG00118 events14 affected211 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 20.0	Systematic Assessment	EG0009 events7 affected209 at risk EG00115 events12 affected211 at risk