A Study Comparing LY900014 to Insulin Lispro (Humalog) in... | NCT03740919

ID	Type	Description	Link
I8B-MC-ITSB	Other Identifier	Eli Lilly and Company
2018-002371-18	EudraCT Number

A Study Comparing LY900014 to Insulin Lispro (Humalog) in... | NCT03740919 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Insulin Lispro (Humalog)	Active Comparator	Participants received 100 units per milliliter (U/mL) insulin lispro (Humalog) administered subcutaneously (SC), 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.	Drug: Insulin Lispro Drug: Insulin Glargine Drug: Insulin Degludec
LY900014	Experimental	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	Drug: LY900014
LY900014 Postmeal	Experimental	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.	Drug: LY900014

Name	Type	Description	Arm Group Labels	Other Names
LY900014	Drug	Administered SC	LY900014 LY900014 Postmeal

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26	Change from baseline in HbA1c was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors. The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26.	Baseline, Week 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in HbA1c (Postprandial) at Week 26	Change from baseline in HbA1c postprandial was analyzed using (MMRM and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors. The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26.

Contacts/Locations Module

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
University of Alabama Birmingham		Birmingham	Alabama	35233	United States
University of Arizona

References Module

Label	URL
A Study Comparing LY900014 to Insulin Lispro (Humalog) in Children and Adolescents With Type 1 Diabetes	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Insulin Lispro (Humalog) Lead-in	Participants were switched to open-label insulin lispro (Humalog) administered subcutaneously (SC), using a unit for unit conversion or the dose could have been determined based on investigator's clinical judgement.
FG001	Insulin Lispro (Humalog)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Apr 30, 2020	Oct 13, 2021

Type	Comment	Reasons
Lost to Follow-up		FG0001 subjects FG0010 subjects FG0020 subjects FG0030 subjects
Physician Decision		FG0002 subjects FG0010 subjects FG0020 subjects FG0030 subjects
Protocol Violation		FG0001 subjects FG0010 subjects FG0020 subjects FG0030 subjects
Withdrawal by Subject		FG00010 subjects FG0010 subjects FG0020 subjects FG0030 subjects
Due to Coronavirus Disease 2019 (COVID-19)		FG00018 subjects FG0010 subjects FG0020 subjects FG0030 subjects
Study Task Too Burdensome		FG0001 subjects FG0010 subjects FG0020 subjects FG0030 subjects
Lab Results Did Not Match Inclusion Criteria		FG0001 subjects FG0010 subjects FG0020 subjects FG0030 subjects
Withdrew Consent Due to Required Procedures		FG0001 subjects FG0010 subjects FG0020 subjects FG0030 subjects

Treatment Period

Type	Comment	Milestone Data
STARTED	After completion of Lead-in Period, participants were randomized to either blinded LY900014 or Humalog or open-label LY900014.	FG0000 subjects FG001298 subjectsParticipants were randomized from Lead-in Period to Insulin Lispro (Humalog). FG002280 subjectsParticipants were randomized from Lead-in Period to LY900014. FG003138 subjectsParticipants were randomized from Lead-in Period to open-label LY900014.
Received at Least One Dose of Study Drug		FG0000 subjects FG001298 subjects FG002280 subjects FG003138 subjects
COMPLETED		FG0000 subjects FG001288 subjects FG002266 subjects FG003135 subjects
NOT COMPLETED		FG0000 subjects FG00110 subjects FG00214 subjects FG0033 subjects

Type	Comment	Reasons
Adverse Event		FG0000 subjects FG0010 subjects FG0022 subjects FG003

Arm/Group Information

ID	Title	Description
BG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.
BG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
BG002	LY900014 Postmeal	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00012.4± 3.2 BG00112.1± 3.4 BG00212.3± 3.8 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000140 BG001144 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0006 BG0016 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00051 BG00155 BG002

HbA1c at Baseline

Mean

Standard Deviation

percentage of HbA1c

Title

Denominators

Categories

Title	Measurements
	BG0007.81± 0.91 BG0017.81± 0.87 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26

Change from baseline in HbA1c was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors.

The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26.

All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug, per protocol.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline, Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets
OG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.

Units	Counts
Participants	OG000280 OG001260

Title

Denominators

Categories

Title	Measurements
	OG0000.09± 0.052 OG0010.06± 0.054

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		0.783		Least Squares (LS) Mean Difference	-0.02			2-Sided	95	-0.17	0.13					Non-Inferiority	Noninferiority margin [NIM]=0.4% for HbA1c

Secondary

Change From Baseline in HbA1c (Postprandial) at Week 26

Change from baseline in HbA1c postprandial was analyzed using (MMRM and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors.

The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26.

All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug, per protocol.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline, Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets
OG001	LY900014 Postmeal	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.

Secondary

Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose

Documented post-dose hypoglycemia <54 milligrams per deciliter (mg/dL) and ≤ 70 mg/dL that occurred 1 and 2 hours after prandial dose.

All randomized participants who received at least one dose of the randomly assigned study drug with non-missing baseline value and at least one non-missing post-baseline value of the response variable.

Posted

Least Squares Mean

Standard Error

percentage of participants

Baseline through Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets
OG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
OG002	LY900014 Postmeal	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.

Secondary

Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose

Documented post-dose hypoglycemia event is an event of blood glucose of < 54 mg/dL and ≤70 mg/dL that occurred within 1 and 2 hours after the prandial dose. The rate of documented hypoglycemia was estimated by a negative binomial regression including treatment and age group as independent variable and number of episodes as dependent variables with log (exposure/365.25 days) as the offset in the model.

Posted

Least Squares Mean

Standard Error

Events per participant per year

Baseline through Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets
OG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
OG002	LY900014 Postmeal

Secondary

Percentage of Participants With Documented Hypoglycemic Events

Documented hypoglycemia is defined as <54 mg/dL and ≤70 mg/dL, respectively.

Posted

Least Squares Mean

Standard Error

percentage of participants

Baseline through Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets
OG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
OG002	LY900014 Postmeal	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.

Secondary

Rate of Documented Hypoglycemia Events

Documented hypoglycemia is defined as a hypoglycemic event of blood glucose of ≤70 mg/dL or <54 mg/dL. The rate of documented hypoglycemia was estimated by negative binomial regression including treatment and age group as independent variables and number of episodes as dependent variable with log (exposure/365.25 days) as the offset in the model.

Posted

Least Squares Mean

Standard Error

events per participant per year

Week 0 through Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets
OG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
OG002	LY900014 Postmeal	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.

Secondary

Rate of Severe Hypoglycemia

Severe hypoglycemia: during these episodes, participants have an altered mental status and cannot assist in their own care, may be semiconscious or unconscious, or experience coma with or without seizures, and require assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.

The rate of severe hypoglycemia per 100 years was calculated as: 100 times the total number of severe hypoglycemia episodes within the period divided by total exposure (in year) for all participants within the treatment group.

Posted

Number

Events per participant per 100 years

Week 0 through Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets
OG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
OG002	LY900014 Postmeal

Secondary

Change From Baseline in Insulin Dose at Week 26

Change from baseline in insulin dose was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, age group, and HbA1c stratum (≤8.0%, >8.0%)), baseline value, visit and treatment-by-visit interaction. An unstructured covariance structure was used to model the within-participant errors.

All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug.

Posted

Least Squares Mean

Standard Error

Unit per day

Baseline, Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets
OG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
OG002	LY900014 Postmeal	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.

Secondary

Percentage of Participants With HbA1c < 7.0% and <7.5%

Percentage of participants with HbA1c < 7.0% and <7.5% was analyzed using a longitudinal logistic regression with repeated measurements conducted by a generalized linear mixed model including independent variables of treatment, baseline HbA1c value, visit, baseline HbA1c-by-visit interaction, and treatment-by-visit interaction. An unstructured covariance structure was used.

All participants who were randomly assigned to study drug and had non-missing baseline value and at least one non-missing post-baseline value of the response variable.

Posted

Number

percentage of participants

Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets
OG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
OG002	LY900014 Postmeal	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.

Secondary

Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26

Change from baseline in 7-point SMBG values were analyzed using MMRM and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group, and HbA1c stratum (≤8.0%, >8.0%)) baseline value, visit, and treatment-by-visit interaction. An unstructured covariance structure was used to model the within-participant errors.

All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, Week 26

ID	Title	Description
OG000	Insulin Lispro (Humalog)	Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.
OG001	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.
OG002	LY900014 Postmeal	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Humalog Lead-in	Participants received open-label insulin lispro (Humalog) administered subcutaneously (SC), using a unit for unit conversion or the dose was determined based on the investigator's clinical judgement.	751	2	751	39	751
EG001	Humalog	Participants received 100 U/mL insulin lispro (Humalog) administered subcutaneously (SC), 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.	298	12	298	60	298
EG002	LY900014	Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	280	6	280	67	280
EG003	LY900014 Postmeal	Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.	138	2	138	21	138

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Macroglossia	Congenital, familial and genetic disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG0030 events0 affected138 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0010 events0 affected298 at risk EG0021 events1 affected280 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG003
Anaphylactic reaction	Immune system disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG003
Complicated appendicitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0010 events0 affected298 at risk EG0020 events0 affected280 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG003
Pilonidal cyst	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0010 events0 affected298 at risk EG0021 events1 affected280 at risk EG003
Reactive gastropathy	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG003
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG003
Diabetic ketoacidosis	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0010 events0 affected298 at risk EG0022 events2 affected280 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected751 at risk EG0012 events2 affected298 at risk EG0023 events3 affected280 at risk EG003
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0010 events0 affected298 at risk EG0021 events1 affected280 at risk EG003
Hypoglycaemic coma	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0000 events0 affected751 at risk EG0011 events1 affected298 at risk EG0020 events0 affected280 at risk EG003
Mental disorder	Psychiatric disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected751 at risk EG0010 events0 affected298 at risk EG0020 events0 affected280 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Vomiting	Gastrointestinal disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected751 at risk EG00111 events9 affected298 at risk EG00210 events9 affected280 at risk EG0033 events3 affected138 at risk
Injection site reaction	General disorders	MedDRA 24.0	Systematic Assessment	EG0001 events1 affected751 at risk EG0010 events0 affected298 at risk EG00214 events11 affected280 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG00021 events21 affected751 at risk EG00130 events23 affected298 at risk EG00237 events28 affected280 at risk EG003
Rhinitis	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0007 events7 affected751 at risk EG00110 events10 affected298 at risk EG0026 events6 affected280 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 24.0	Systematic Assessment	EG0003 events3 affected751 at risk EG00118 events16 affected298 at risk EG00217 events15 affected280 at risk EG003
Headache	Nervous system disorders	MedDRA 24.0	Systematic Assessment	EG0006 events6 affected751 at risk EG00121 events13 affected298 at risk EG00222 events13 affected280 at risk EG003

Ancestor Terms

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

Ancestor Terms

ID	Term
D061266	Insulin, Short-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
D049528	Insulin, Long-Acting

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		0.867		LS Mean Difference	-0.02			2-Sided	95	-0.20	0.17					Non-Inferiority	NIM of 0.4%

Title

Denominators

Categories

<54 mg/dL 1 Hour Post Dose

Title	Measurements
	OG00026.50± 2.563 OG00136.79± 2.891 OG00229.70± 3.897

<54 mg/dL 2 Hour Post Dose

Title	Measurements
	OG00054.04± 2.896 OG00163.61± 2.883 OG00257.88± 4.216

≤70 mg/dL 1 Hour Post Dose

Title	Measurements
	OG00049.67± 2.901 OG00163.92± 2.874 OG00248.51± 4.261

≤70 mg/dL 2 Hour Post Dose

Title	Measurements
	OG00077.03± 2.449 OG00182.67± 2.267 OG00270.29± 3.912

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	< 54 mg/dL 1 hour post-dose	Regression, Logistic	0.008	Odds Ratio (OR)	1.61	2-Sided	95	1.13	2.30	Superiority
OG000 OG002	< 54 mg/dL 1 hour post-dose	Regression, Logistic	0.487	Odds Ratio (OR)	1.17	2-Sided	95	0.75	1.83	Superiority
OG001 OG002	< 54 mg/dL 1 hour post-dose	Regression, Logistic	0.153	Odds Ratio (OR)	0.73	2-Sided	95	0.47	1.13	Superiority
OG000 OG001	< 54 mg/dL 2 hour post-dose	Regression, Logistic	0.020	Odds Ratio (OR)	1.49	2-Sided	95	1.06	2.08	Superiority
OG000 OG002	< 54 mg/dL 2 hour post-dose	Regression, Logistic	0.455	Odds Ratio (OR)	1.17	2-Sided	95	0.78	1.76	Superiority
OG001 OG002	< 54 mg/dL 2 hour post-dose	Regression, Logistic	0.259	Odds Ratio (OR)	0.79	2-Sided	95	0.52	1.19	Superiority
OG000 OG001	≤ 70 mg/dL 1 hour post-dose	Regression, Logistic	<0.001	Odds Ratio (OR)	1.79	2-Sided	95	1.29	2.51	Superiority
OG000 OG002	≤ 70 mg/dL 1 hour post-dose	Regression, Logistic	0.822	Odds Ratio (OR)	0.95	2-Sided	95	0.64	1.43	Superiority
OG001 OG002	≤ 70 mg/dL 1 hour post-dose	Regression, Logistic	0.003	Odds Ratio (OR)	0.53	2-Sided	95	0.35	0.80	Superiority
OG000 OG001	≤ 70 mg/dL 2 hour post-dose	Regression, Logistic	0.092	Odds Ratio (OR)	1.42	2-Sided	95	0.94	2.14	Superiority
OG000 OG002	≤ 70 mg/dL 2 hour post-dose	Regression, Logistic	0.133	Odds Ratio (OR)	0.71	2-Sided	95	0.45	1.11	Superiority
OG001 OG002	≤ 70 mg/dL 2 hour post-dose	Regression, Logistic	0.004	Odds Ratio (OR)	0.50	2-Sided	95	0.31	0.80	Superiority

Title

Denominators

Categories

< 54mg/dL 1 Hour Post Dose

Title	Measurements
	OG0001.59± 0.251 OG0012.04± 0.262 OG0021.38± 0.287

< 54 mg/dL 2 Hour Post Dose

Title	Measurements
	OG0004.48± 0.454 OG0015.95± 0.510 OG0026.17± 0.816

≤70 mg/dL 1 Hour Post Dose

Title	Measurements
	OG0006.54± 1.036 OG0018.46± 0.992 OG0025.29± 1.145

≤70 mg/dL 2 Hour Post Dose

Title	Measurements
	OG00019.0± 1.58 OG00123.7± 1.86 OG00221.1± 2.31

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	Non-Inferiority Type
OG000 OG001	< 54 mg/dL 1 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.220	Superiority
OG000 OG002	< 54 mg/dL 1 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.599	Superiority
OG001 OG002	< 54 mg/dL 1 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.112	Superiority
OG000 OG001	< 54 mg/dL 2 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.034	Superiority
OG000 OG002	< 54 mg/dL 2 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.055	Superiority
OG001 OG002	< 54 mg/dL 2 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.814	Superiority
OG000 OG001	≤70 mg/dL 1 hour post-dose	Negative binomial regression		0.194	Superiority
OG000 OG002	≤70 mg/dL 1 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.428	Superiority
OG001 OG002	≤70 mg/dL 1 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.057	Superiority
OG000 OG001	≤70 mg/dL 2 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model	0.056	Superiority
OG000 OG002	≤70 mg/dL 2 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.435	Superiority
OG001 OG002	≤70 mg/dL 2 hour post-dose	Negative binomial regression	Treatment and age group as covariates, log (exposure/365.25 days) as the offset in the model.	0.404	Superiority

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	<54 mg/dL	Regression, Logistic	0.864	Odds Ratio (OR)	1.04	2-Sided	95	0.68	1.57	Superiority
OG000 OG002	<54 mg/dL	Regression, Logistic	0.132	Odds Ratio (OR)	0.69	2-Sided	95	0.43	1.12	Superiority
OG001 OG002		Regression, Logistic	0.104	Odds Ratio (OR)	0.67	2-Sided	95	0.41	1.09	Superiority
OG000 OG001	≤70 mg/dL	Regression, Logistic	0.489	Odds Ratio (OR)	0.80	2-Sided	95	0.42	1.52	Superiority
OG000 OG002	≤70 mg/dL	Regression, Logistic	0.025	Odds Ratio (OR)	0.45	2-Sided	95	0.23	0.90	Superiority
OG001 OG002	≤70 mg/dL	Regression, Logistic	0.099	Odds Ratio (OR)	0.57	2-Sided	95	0.29	1.11	Superiority

Group IDs	Group Description	Statistical Method	P-Value	Non-Inferiority Type
OG000 OG001	< 54 mg/dL	Negative binomial regression	0.732	Superiority
OG000 OG002	< 54 mg/dL	Negative binomial regression	0.638	Superiority
OG001 OG002	<54 mg/dL	Negative binomial regression	0.462	Superiority
OG000 OG001	≤ 70 mg/dL	Negative binomial regression	0.632	Superiority
OG000 OG002	≤ 70 mg/dL	Negative binomial regression	0.800	Superiority
OG001 OG002	≤ 70 mg/dL	Negative binomial regression	0.889	Superiority

Title

Denominators

Categories

Total Daily Basal Insulin Dose

- ParticipantsOG000283
- ParticipantsOG001264
- ParticipantsOG002132

Title	Measurements
	OG0002.3± 0.28 OG0012.9± 0.29 OG0022.7± 0.40

Total Daily Insulin Dose

- ParticipantsOG000279
- ParticipantsOG001256
- ParticipantsOG002131

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	Total Daily Basal Insulin	Mixed Models Analysis	0.130	LS Mean Difference	0.6	2-Sided	95	-0.2	1.4	Superiority
OG000 OG002	Total Daily Basal Insulin	Mixed Models Analysis	0.404	LS Mean Difference	0.4	2-Sided	95	-0.5	1.4	Superiority
OG001 OG002	Total Daily Basal Insulin	Mixed Models Analysis	0.693	LS Mean Difference	-0.2	2-Sided	95	-1.2	0.8	Superiority
OG000 OG001	Total Daily Insulin Dose	Mixed Models Analysis	0.625	LS Mean Difference	0.5	2-Sided	95	-1.4	2.3	Superiority
OG000 OG002	Total Daily Insulin Dose	Mixed Models Analysis	0.758	LS Mean Difference	-0.4	2-Sided	95	-2.6	1.9	Superiority
OG001 OG002	Total Daily Insulin Dose	Mixed Models Analysis	0.485	Mean Difference (Final Values)	-0.8	2-Sided	95	-3.1	1.5	Superiority

Group IDs	Group Description	Statistical Method	P-Value	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type
OG000 OG001	HbA1c < 7%	Regression, Logistic	0.396	Odds Ratio (OR)	1.23	2-Sided	95	0.76	2.00	Superiority
OG000 OG002	HbA1c < 7%	Regression, Logistic	0.814	Odds Ratio (OR)	0.93	2-Sided	95	0.49	1.75	Superiority
OG001 OG002	HbA1c < 7%	Regression, Logistic	0.384	Odds Ratio (OR)	0.75	2-Sided	95	0.39	1.43	Superiority
OG000 OG001	HbA1c < 7.5%	Regression, Logistic	0.400	Odds Ratio (OR)	0.84	2-Sided	95	0.55	1.27	Superiority
OG000 OG002	HbA1c < 7.5%	Regression, Logistic	0.094	Odds Ratio (OR)	0.62	2-Sided	95	0.36	1.08	Superiority
OG001 OG002	HbA1c < 7.5%	Regression, Logistic	0.306	Odds Ratio (OR)	0.75	2-Sided	95	0.43	1.31	Superiority

Title

Denominators

Categories

Morning Premeal - Fasting

- ParticipantsOG000265
- ParticipantsOG001247
- ParticipantsOG002122

Title	Measurements
	OG0001.0± 2.78 OG001-3.4± 2.88 OG002-5.9± 4.11

Morning 1 hour Postmeal

- ParticipantsOG000263
- ParticipantsOG001239
- ParticipantsOG002117

Title	Measurements
	OG000

Midday Premeal

- ParticipantsOG000265
- ParticipantsOG001247
- ParticipantsOG002122

Title	Measurements
	OG000

Midday 1 hour Postmeal

- ParticipantsOG000262
- ParticipantsOG001237
- ParticipantsOG002120

Title	Measurements
	OG000

Evening Premeal

- ParticipantsOG000264
- ParticipantsOG001247
- ParticipantsOG002122

Title	Measurements
	OG000

Evening 1 hour Postmeal

- ParticipantsOG000261
- ParticipantsOG001234
- ParticipantsOG002118

Title	Measurements
	OG000

Bedtime

- ParticipantsOG000257
- ParticipantsOG001240
- ParticipantsOG002116

Title	Measurements
	OG000

ID	Term
D061268	Insulin Lispro
D000069036	Insulin Glargine
C571886	insulin degludec