A Study of LY3209590 in Participants With Type 1 Diabetes | NCT04450407

NCT04450407

ID	Type	Description	Link
I8H-MC-BDCP	Other Identifier	Eli Lilly and Company
2019-003589-41	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
LY3209590 Algorithm 1 (Paper)	Experimental	Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 milligram (mg) vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by subcutaneous (SC) injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 milligrams per deciliter (mg/dL).	Drug: LY3209590
LY3209590 Algorithm 2 (Digital)	Experimental	Algorithm 2 is a computer-based algorithm to determine dose adjustments. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL. As per protocol amendment (d) approved on 28-Oct-2020, this arm was terminated during the early enrollment phase due to technical issues with data entry.	Drug: LY3209590
Insulin Degludec	Active Comparator	Insulin degludec was provided as 100 units/milliliter (U/mL) in a prefilled pen. Participants received individually adjusted doses once daily by SC injection with a starting dose same as basal insulin dose prior randomization, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.	Drug: Insulin Degludec

Name	Type	Description	Arm Group Labels	Other Names
LY3209590	Drug	Administered SC	LY3209590 Algorithm 1 (Paper) LY3209590 Algorithm 2 (Digital)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Hemoglobin A1c (HbA1c)	HbA1c is the glycosylated fraction of haemoglobin A. It is measured to identify average blood glucose concentration over prolonged periods of time. Least squares (LS) mean change from baseline was analysed by mixed model repeated measures (MMRM) model with treatment, country, visit, and treatment by visit interaction as fixed effects and the baseline HbA1c as a covariate.	Baseline, Week 26

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Fasting Serum Glucose	LS mean change from baseline was analysed by mixed model repeated measures (MMRM) model with treatment, country, HbA1c stratum, visit, and treatment by visit interaction as fixed effects and the baseline fasting serum glucose as a covariate.	Baseline, Week 26

Eligibility Module

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 - 5hours, EST)	Eli Lilly and Company	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
John Muir Physician Network Clinical Research Center		Concord	California	94520	United States
Valley Endocrine, Fresno

References Module

Label	URL
A Study of LY3209590 in Participants With Type 1 Diabetes	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	LY3209590 Algorithm 1 (Paper)	Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 milligram (mg) vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by subcutaneous (SC) injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 milligrams per deciliter (mg/dL).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

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	Oct 28, 2020	Sep 9, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

All randomized participants.

Arm/Group Information

ID	Title	Description
BG000	LY3209590 Algorithm 1 (Paper)	Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL.
BG001	LY3209590 Algorithm 2 (Digital)	Algorithm 2 is a computer-based algorithm to determine dose adjustments. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL.
BG002	Insulin Degludec	Insulin degludec was provided as 100 U/mL in a prefilled pen. Participants received individually adjusted doses once daily by SC injection with a starting dose same as basal insulin dose prior randomization, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.
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
	ParticipantsBG000124 ParticipantsBG00116 ParticipantsBG002126 ParticipantsBG003

Sex: Female, Male

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000124 ParticipantsBG00116 ParticipantsBG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000124 ParticipantsBG00116 ParticipantsBG002

Race (NIH/OMB)

Count of Participants

Participants

Title	Denominators	Categories
	ParticipantsBG000124 ParticipantsBG00116 ParticipantsBG002

Region of Enrollment

Count of Participants

Participants

Title	Denominators	Categories
Puerto Rico	ParticipantsBG000124 ParticipantsBG00116 ParticipantsBG002

Haemoglobin A1c (HbA1c)

HbA1c is the glycosylated fraction of haemoglobin A. It is measured to identify average blood glucose concentration over prolonged periods of time.

All randomized participants with HbA1c data at baseline.

Mean

Standard Deviation

Percentage of HbA1c

Title	Denominators	Categories
	ParticipantsBG000124 ParticipantsBG00116 ParticipantsBG002

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 haemoglobin A. It is measured to identify average blood glucose concentration over prolonged periods of time. Least squares (LS) mean change from baseline was analysed by mixed model repeated measures (MMRM) model with treatment, country, visit, and treatment by visit interaction as fixed effects and the baseline HbA1c as a covariate.

All participants randomized to either LY3209590 Algorithm 1 (Paper) or Insulin degludec, received at least one dose of study drug and had baseline, post-baseline HbA1c data prior to treatment discontinuation.

Posted

Least Squares Mean

Standard Error

Percentage of HbA1c

Baseline, Week 26

ID	Title	Description
OG000	LY3209590 Algorithm 1 (Paper)	Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL.
OG001	Insulin Degludec	Insulin degludec was provided as 100 U/mL in a prefilled pen. Participants received individually adjusted doses once daily by SC injection with a starting dose same as basal insulin dose prior randomization, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.

Units	Counts
Participants	OG000118 OG001123

Title

Denominators

Categories

Title	Measurements
	OG0000.04± 0.068 OG001-0.13± 0.065

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						LS Mean Difference	0.17			2-Sided	90	0.01	0.32					Non-Inferiority	The non-inferiority margin is 0.4%. Non-inferiority is achieved if the upper limit of the 90% CI (Confidence Interval) is below 0.4.

Secondary

Change From Baseline in Fasting Serum Glucose

LS mean change from baseline was analysed by mixed model repeated measures (MMRM) model with treatment, country, HbA1c stratum, visit, and treatment by visit interaction as fixed effects and the baseline fasting serum glucose as a covariate.

All participants randomized to either LY3209590 Algorithm 1 (Paper) or Insulin degludec, received at least one dose of study drug and had baseline, post-baseline fasting serum glucose data prior to treatment discontinuation.

Posted

Least Squares Mean

Standard Error

milligrams per deciliter (mg/dL)

Baseline, Week 26

ID	Title	Description
OG000	LY3209590 Algorithm 1 (Paper)	Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL.
OG001	Insulin Degludec	Insulin degludec was provided as 100 U/mL in a prefilled pen. Participants received individually adjusted doses once daily by SC injection with a starting dose same as basal insulin dose prior randomization, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.

Secondary

Change From Baseline in Bolus Insulin Dose

Bolus insulin dose was the sum of doses for morning, midday, evening meals, snack and correction. LS mean change from baseline was analysed by MMRM model with treatment, country, HbA1c stratum, visit, and treatment by visit interaction as fixed effects and the baseline bolus insulin dose as a covariate.

All participants randomized to either LY3209590 Algorithm 1 (Paper) or Insulin degludec, received at least one dose of study drug and had baseline, post-baseline bolus insulin dose data prior to treatment discontinuation.

Posted

Least Squares Mean

Standard Error

Units per kilogram per day (U/kg/day)

Baseline, Week 26

ID	Title	Description
OG000	LY3209590 Algorithm 1 (Paper)	Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL.
OG001	Insulin Degludec	Insulin degludec was provided as 100 U/mL in a prefilled pen. Participants received individually adjusted doses once daily by SC injection with a starting dose same as basal insulin dose prior randomization, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.

Secondary

Rate of Documented Hypoglycemia

Documented hypoglycemia is defined as any time a participant reports a self-monitoring blood glucose <54 mg/dL (3.0 millimole per liter (mmol/L)). Negative binomial model using baseline hypoglycaemia incidence, baseline HbA1c and treatment as independent variables was performed to estimate the event rate. Data presented is group mean. Group Mean is estimated by first taking the inverse link function on individual participant covariates, then averaging over all participants.

All participants randomized to either LY3209590 Algorithm 1 (Paper) or Insulin degludec, received at least one dose of study drug.

Posted

Mean

Standard Error

Events per participant per year

Baseline through Week 26

ID	Title	Description
OG000	LY3209590 Algorithm 1 (Paper)	Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL.
OG001	Insulin Degludec	Insulin degludec was provided as 100 U/mL in a prefilled pen. Participants received individually adjusted doses once daily by SC injection with a starting dose same as basal insulin dose prior randomization, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.

Secondary

Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3209590

AUC of LY3209590 was calculated for individual participants using the participant's Week 26 LY3209590 dose amount and the estimated clearance value.

All participants randomized to LY3209590 Algorithm 1 (Paper), received at least one dose of study drug and had evaluable PK data at Week 26.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanomole*hour per Liter (nmol*hr/L)

Week 26

ID	Title	Description
OG000	LY3209590 Algorithm 1 (Paper)	Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	LY3209590 Algorithm 1 (Paper)	Algorithm 1 is a paper-based algorithm where dose adjustments were manually determined by the investigator based on fasting glucose and hypoglycemia data. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL.	124	5	124	21	124
EG001	LY3209590 Algorithm 2 (Digital)	Algorithm 2 is a computer-based algorithm to determine dose adjustments. LY3209590 was provided in a 20 mg vial of reconstitutable lyophilized powder. Participants received individualized LY3209590 loading dose based on the basal insulin dose prior randomization and baseline fasting glucose by SC injection on day 1 followed by weekly adjustments for the first 12 weeks, then every 4 weeks, of a 26-week treatment period, to achieve target fasting glucose of <=100 mg/dL.	16	0	16	7	16
EG002	Insulin Degludec	Insulin degludec was provided as 100 U/mL in a prefilled pen. Participants received individually adjusted doses once daily by SC injection with a starting dose same as basal insulin dose prior randomization, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.	126	4	126	11	126

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected124 at risk EG0010 events0 affected16 at risk EG0021 events1 affected126 at risk
Coronary artery stenosis	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected124 at risk EG0010 events0 affected16 at risk EG0021 events1 affected126 at risk
Pneumonia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected16 at risk EG0020 events0 affected126 at risk
Maternal exposure during pregnancy	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected50 at risk EG0010 events0 affected4 at risk EG0020 events0 affected48 at risk
Patella fracture	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected124 at risk EG0010 events0 affected16 at risk EG0021 events1 affected126 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected16 at risk EG0022 events1 affected126 at risk
Facet joint syndrome	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected16 at risk EG0020 events0 affected126 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected124 at risk EG0010 events0 affected16 at risk EG0021 events1 affected126 at risk
Depression	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected16 at risk EG0020 events0 affected126 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Injection site bruising	General disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected124 at risk EG0011 events1 affected16 at risk EG0020 events0 affected126 at risk
Covid-19	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected124 at risk EG0011 events1 affected16 at risk EG0022 events2 affected126 at risk
Nasopharyngitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0004 events3 affected124 at risk EG0011 events1 affected16 at risk EG0021 events1 affected126 at risk
Onychomycosis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected124 at risk EG0011 events1 affected16 at risk EG0020 events0 affected126 at risk
Sinusitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected124 at risk EG0011 events1 affected16 at risk EG0021 events1 affected126 at risk
Hepatic enzyme increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected124 at risk EG0012 events1 affected16 at risk EG0021 events1 affected126 at risk
Sars-cov-2 test positive	Investigations	MedDRA 24.1	Systematic Assessment	EG0002 events2 affected124 at risk EG0011 events1 affected16 at risk EG0020 events0 affected126 at risk
Headache	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG00014 events10 affected124 at risk EG0010 events0 affected16 at risk EG0025 events5 affected126 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected124 at risk EG0011 events1 affected16 at risk EG0020 events0 affected126 at risk
Hypertension	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0004 events4 affected124 at risk EG0011 events1 affected16 at risk EG0023 events3 affected126 at risk

The study was initially designed as 3 arms: LY3209590 Algorithm 1 (Paper), LY3209590 Algorithm 2 (Digital), and Insulin Degludec. However, it was amended to terminate the "LY3209590 Algorithm 2 (Digital)" arm during early enrollment phase due to technical issues with data entry. Thus, this arm was excluded from the outcome measure analyses, but safety data was analysed and reported.

Certain Agreements

ID	Term
D003922	Diabetes Mellitus, Type 1

Ancestor Terms

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

ID	Term
C571886	insulin degludec

ParticipantsBG003266

ParticipantsBG003265