Study of Human Regular U-500 Insulin in Adult Participant... | NCT01774968

ID	Type	Description	Link
B5K-US-IBHC	Other Identifier	Eli Lilly and Company

Label	Type	Description	Intervention Names
Human Regular U-500 Insulin TID	Experimental	Human Regular U-500 Insulin (U-500R) titrated based on blood glucose readings, administered subcutaneously (SC), three times a day (TID) for 24 weeks.	Drug: Human Regular U-500 Insulin
Human Regular U-500 Insulin BID	Experimental	U-500R Insulin titrated based on blood glucose readings, administered SC, two times a day (BID) for 24 weeks.	Drug: Human Regular U-500 Insulin

Name	Type	Description	Arm Group Labels	Other Names
Human Regular U-500 Insulin	Drug		Human Regular U-500 Insulin BID Human Regular U-500 Insulin TID	LY041001

Measure	Description	Time Frame
Change From Baseline to Week 24 in Glycated Hemoglobin A1c (HbA1c)	Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with investigator, baseline total daily dose (TDD; ≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.	Baseline, Week 24

Measure	Description	Time Frame
Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24	The percentage of participants achieving an HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100.	Week 24

Eligibility Module

Eligibility Criteria

Major Inclusion Criteria:

Have type 2 diabetes mellitus (World Health Organization [WHO] Classification of Diabetes)
Have a body mass index (BMI) ≥25 kilogram per square meter (kg/m^2)
Have Glycated Hemoglobin A1c (HbA1c) ≥7.5% and ≤12.0%, as measured by the central laboratory at entry
Current U-100 insulin/analogue users on >200 and ≤600 units per day for ≥3 months at study entry and reconfirmed at randomization
Have a history of stable body weight for at least 3 months prior to study entry
Concomitant medications may include metformin (MET), dipeptidyl peptidase-4 (DPP-4) inhibitors approved for use with insulin at time of study entry (for example, sitagliptin, saxagliptin, and linagliptin), pioglitazone, and/or sulfonylureas (SUs)/glinides (repaglinide or nateglinide). Participant's oral antihyperglycemic drug (OAD) dose(s) must have been stable for ≥3 months

Major Exclusion Criteria:

Have type 1 diabetes mellitus or other types of diabetes mellitus apart from type 2 diabetes mellitus
Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine aminotransferase or aspartate aminotransferase levels ≥3 times the upper limit of the reference range
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 study entry
Have received insulin by continuous subcutaneous insulin infusion in the 3 months prior to study entry
Have received U-500R in the 3 months prior to study entry
Have had a blood transfusion or severe blood loss within 3 months prior to study entry or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia
Are taking chronic systemic glucocorticoid therapy or have received such therapy within the 4 weeks immediately prior to study entry
Have an irregular sleep/wake cycle
Have used rosiglitazone, once- or twice-daily glucagon-like peptide-1 (GLP-1) receptor agents, pramlintide, or other injectable or oral antihyperglycemic therapy not listed in the inclusion criteria in the 3 months prior to study entry. Participants may not have used once-weekly GLP-1 receptor agents in the 4 months prior to study entry
Have used any weight loss drugs in the 3 months prior to study entry
Have a history of bariatric surgery
Have a history of malignancy other than basal cell or squamous cell skin cancer
Have New York Heart Association (NYHA) Class III or IV per NYHA Cardiac Disease Functional Classification
Are breastfeeding or pregnant, or intend to become pregnant during the course of the study, or are sexually active women of childbearing potential not actively practicing birth control by a method determined by the investigator to be medically acceptable

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
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.		Mobile	Alabama	36617

PubMed Identifier	Type	Citation	Retractions
27716283	Derived	Kabul S, Hood RC, Duan R, DeLozier AM, Settles J. Patient-reported outcomes in transition from high-dose U-100 insulin to human regular U-500 insulin in severely insulin-resistant patients with type 2 diabetes: analysis of a randomized clinical trial. Health Qual Life Outcomes. 2016 Sep 30;14(1):139. doi: 10.1186/s12955-016-0541-4.
26307903

ID	Title	Description
FG000	Human Regular U-500 Insulin TID	Human Regular U-500 Insulin (U-500R) titrated based on blood glucose readings, administered subcutaneously (SC), three times a day (TID) for 24 weeks.
FG001	Human Regular U-500 Insulin BID

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 to Week 24 in Glycated Hemoglobin A1c (HbA1c)

Least Squares (LS) means of change from baseline were calculated using a mixed-effects model for repeated measures (MMRM) with investigator, baseline total daily dose (TDD; ≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.

Randomized participants who received at least 1 dose of U-500R with evaluable HbA1c data.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants	OG000162 OG001161

Title

Denominators

Categories

Title	Measurements
	OG000-1.12± 0.08 OG001-1.22± 0.08

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	Approximately 325 participants were to be randomized (in a 1:1 ratio of U-500R insulin TID:BID) and 260 were to complete the study (with a 20% dropout rate). The 260 completers would provide a 66.4% chance to show equivalence of TID and BID algorithms, 14.4% chance to show noninferiority of TID, 2.5% chance to superiority of TID, 14.4% chance to show noninferiority of BID, and 2.5% chance to show superiority of BID, assuming a difference in HbA1c change of 0% and a standard deviation of 1.1%.	Mixed Models Analysis		0.3709		LS Mean Difference	-0.10			2-Sided	95	-0.33	0.12				Yes	Non-Inferiority or Equivalence

Secondary

Percentage of Participants Achieving HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24

The percentage of participants achieving an HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% at Week 24 was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100.

Randomized participants who received at least 1 dose of U-500R, who were not at the HbA1c target at baseline, and had evaluable HbA1c data.

Posted

Number

percentage of participants

Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants	OG000

Secondary

30-Day Adjusted Rate of Hypoglycemic Events

Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person [accompanied by neurologic/cognitive impairment]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose [PG] ≤70 milligrams per deciliter [mg/dL]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Randomized participants who received at least 1 dose of U-500R.

Posted

Mean

Standard Deviation

events per participant per 30 days

Baseline through Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units

Secondary

Change From Baseline to Week 24 in Body Weight

LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), baseline TDD (≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate.

Randomized participants who received at least 1 dose of U-500R with evaluable body weight data.

Posted

Least Squares Mean

Standard Error

kilograms (kg)

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 24 in Total Daily Dose (TDD; Units) of Insulin

Baseline TDD was defined as the last U-100 insulin TDD prior to receiving the first dose of U-500R insulin. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline TDD as a covariate.

Randomized participants who received at least 1 dose of U-500R with evaluable TDD data.

Posted

Least Squares Mean

Standard Error

units

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 24 in Total Daily Dose (TDD; Units/kg) of Insulin

Randomized participants who received at least 1 dose of U-500R with evaluable TDD data.

Posted

Least Squares Mean

Standard Error

units per kilogram (units/kg)

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 24 in Fasting Plasma Glucose (FPG) Levels

Randomized participants who received at least 1 dose of U-500R with evaluable FPG data.

Posted

Least Squares Mean

Standard Error

milligrams per deciliter (mg/dL)

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Time to Reach HbA1c Target Values

The cumulative number of participants achieving an HbA1c of ≤6.5%, <7.0%, <7.5%, and <8.0% is summarized at Weeks 6, 12, 18, and 24. The number of participants at risk (n) is also provided for each target value and timepoint.

Randomized participants who received at least 1 dose of U-500R, who were not at the HbA1c target at baseline, and had evaluable HbA1c data

Posted

Number

participants

Baseline through 6, 12, 18, and 24 weeks.

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With Hypoglycemic Events

Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person [accompanied by neurologic/cognitive impairment]), documented symptomatic (an event which is associated with signs/symptoms of hypoglycemia and plasma glucose [PG] ≤70 milligrams per deciliter [mg/dL]), documented symptomatic nocturnal (any documented symptomatic HE that occurred between bedtime and waking), or asymptomatic (any measured PG ≤70 mg/dL not accompanied by hypoglycemic signs/symptoms). The percentage of participants with HE at 24 weeks was calculated by the dividing the number of participants meeting the criteria by the total number of participants analyzed, multiplied by 100. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Randomized participants who received at least 1 dose of U-500R.

Posted

Number

percentage of participants

Baseline through Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Secondary

Change From Baseline to Week 24 in Number of Insulin Injections

The number of insulin injections per day at baseline (Week 0) and at Week 24 are presented.

Randomized participants who received at least 1 dose of U-500R. Last observation carried forward (LOCF) was used to impute missing postbaseline values.

Posted

Mean

Standard Deviation

injections per day

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Mean Change From Baseline to Week 24 in 7-Point Self-Monitored Blood Glucose (SMBG)

The 7-point SMBG is a participant self-administered blood glucose test which utilizes measurements at specific time points over a 24-hour period, including pre-morning meal (fasting), 2 hours after morning meal, pre-midday meal, 2 hours after midday meal, pre-evening meal, 2 hours after evening meal, and 3 AM. LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), baseline TDD (≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline SMBG as a covariate.

Randomized participants who received at least 1 dose of U-500R with evaluable SMBG data.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts

Secondary

Change From Baseline to Week 24 in HbA1c Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg

Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or >2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline TDD (≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline HbA1c as a covariate.

Randomized participants who received at least 1 dose of U-500R with evaluable HbA1c data.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants	OG000

Secondary

Change From Baseline to Week 24 in 30-Day Adjusted Rate of Hypoglycemic Events Based on Baseline TDD Insulin ≤2.0 Units/kg and >2.0 Units/kg

Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or >2.0 units/kg). Hypoglycemic events (HE) were classified as severe (an event requiring assistance from another person [accompanied by neurologic/cognitive impairment]), documented symptomatic (DS; an event which is associated with signs/symptoms of hypoglycemia and plasma glucose [PG] ≤70 milligrams per deciliter [mg/dL]), or nocturnal (Noc; any documented symptomatic HE that occurred between bedtime and waking). The 30-day adjusted rate of HE is summarized cumulatively at 24 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Randomized participants who received at least 1 dose of U-500R.

Posted

Mean

Standard Deviation

events per participant per 30 days

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Secondary

Change From Baseline to Week 24 in Percentage of Participants With Hypoglycemic Events Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg

Participants were stratified by their baseline TDD insulin (≤2.0 units (U)/kg or >2.0 U/kg). The percentage of participants at risk of developing hypoglycemia (including documented symptomatic, asymptomatic, probable symptomatic, unspecified, or severe hypoglycemia) is presented at Baseline and at Week 24 and was calculated using MMRM fit with options of the binomial distribution and log link function including treatment, TDD (>300 units or ≤300 units), pioglitazone use (yes or no), visit, and treatment-by-visit interaction as fixed effects, and baseline HbA1c value as a covariate.

Randomized participants who received at least 1 dose of U-500R.

Posted

Number

percentage of participants

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts

Secondary

Change From Baseline to Week 24 in Body Weight Based on Baseline TDD Insulin ≥2.0 Units/kg and <2.0 Units/kg

Participants were stratified by their baseline TDD insulin (≤2.0 units/kg or >2.0 units/kg). LS means of change from baseline were calculated using MMRM with investigator, baseline HbA1c (≤8% or >8%), baseline TDD (≤300 or >300 units), treatment (TID or BID), visit, and treatment-by-visit interaction as fixed effects and baseline body weight as a covariate.

Randomized participants who received at least 1 dose of U-500R with evaluable body weight data.

Posted

Least Squares Mean

Standard Error

Baseline, Week 24

ID	Title	Description
OG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
OG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.

Units	Counts
Participants

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Leukocytosis	Blood and lymphatic system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0003 events3 affected162 at risk EG0011 events1 affected163 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0002 events1 affected162 at risk EG0013 events3 affected163 at risk
Coronary artery disease	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0012 events1 affected163 at risk
Diastolic dysfunction	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Ischaemic cardiomyopathy	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Myocardial infarction	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Colitis ulcerative	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Dysphagia	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Mesenteric vein thrombosis	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Chest pain	General disorders	MedDRA 17.0	Systematic Assessment	EG0002 events2 affected162 at risk EG0012 events2 affected163 at risk
Non-cardiac chest pain	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Oedema peripheral	General disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Pyrexia	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Portal vein thrombosis	Hepatobiliary disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Cellulitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0003 events2 affected162 at risk EG0011 events1 affected163 at risk
Diverticulitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Localised infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Osteomyelitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0002 events1 affected162 at risk EG0012 events1 affected163 at risk
Pharyngotonsillitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Pneumonia	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0013 events3 affected163 at risk
Muscle strain	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 17.0	Systematic Assessment	EG0003 events3 affected162 at risk EG0016 events6 affected163 at risk
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Tenosynovitis	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Colon cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Endometrial cancer stage i	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 17.0	Systematic Assessment	EG0003 events1 affected162 at risk EG0010 events0 affected163 at risk
Brain injury	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Convulsion	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Viith nerve paralysis	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Post-traumatic stress disorder	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0012 events1 affected163 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0012 events2 affected163 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0012 events1 affected163 at risk
Bronchial hyperreactivity	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0012 events1 affected163 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0012 events2 affected163 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0011 events1 affected163 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 events1 affected162 at risk EG0010 events0 affected163 at risk
Aortic stenosis	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0002 events1 affected162 at risk EG0010 events0 affected163 at risk
Hypertension	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0002 events1 affected162 at risk EG0012 events1 affected163 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 17.0	Systematic Assessment	EG0000 events0 affected162 at risk EG0011 events1 affected163 at risk

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

ID	Term
D011384	Proinsulin
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

ID	Title	Description
BG000	Human Regular U-500 Insulin TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.
BG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 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 TID	U-500R Insulin titrated based on blood glucose readings, administered SC, TID for 24 weeks.			28	162	80	162
EG001	Human Regular U-500 Insulin BID	U-500R Insulin titrated based on blood glucose readings, administered SC, BID for 24 weeks.			27	163	94	163

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0006 events6 affected162 at risk EG00110 events10 affected163 at risk
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0004 events4 affected162 at risk EG0019 events9 affected163 at risk
Vomiting	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0004 events4 affected162 at risk EG00111 events11 affected163 at risk
Oedema peripheral	General disorders	MedDRA 17.0	Systematic Assessment	EG0006 events6 affected162 at risk EG00110 events10 affected163 at risk
Bronchitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0009 events9 affected162 at risk EG0015 events5 affected163 at risk
Nasopharyngitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG00013 events13 affected162 at risk EG00117 events17 affected163 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG00013 events13 affected162 at risk EG0019 events9 affected163 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0003 events3 affected162 at risk EG00110 events10 affected163 at risk
Headache	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG00013 events13 affected162 at risk EG0016 events6 affected163 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0009 events9 affected162 at risk EG0017 events7 affected163 at risk