A Phase 2 Study of LY3209590 in Participants With Type 2... | NCT04450394

ID	Type	Description	Link
I8H-MC-BDCL	Other Identifier	Eli Lilly and Company
2019-003339-53	EudraCT Number

Status Module

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 baseline median fasting glucose and body weight 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 baseline median fasting glucose and body weight 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 of 10 units, 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, Dipeptidyl peptidase IV (DPPIV) (yes/no), Sodium-glucose Cotransporter-2 (SGLT2) (yes/no), baseline body mass index (BMI) [<30, >=30]), 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 MMRM model with treatment, country, DPPIV (yes/no), SGLT2 (yes/no), baseline BMI [<30, >=30]), visit, and treatment by visit interaction as fixed effects and the baseline fasting serum glucose as a covariate.	Baseline, Week 26

Eligibility 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
Syed Research Consultants Llc		Sheffield	Alabama	35660	United States
National Research Institute - Huntington Park

PubMed Identifier	Type	Citation	Retractions
36944059	Derived	Bue-Valleskey JM, Kazda CM, Ma C, Chien J, Zhang Q, Chigutsa E, Landschulz W, Haupt A, Frias JP. Once-Weekly Basal Insulin Fc Demonstrated Similar Glycemic Control to Once-Daily Insulin Degludec in Insulin-Naive Patients With Type 2 Diabetes: A Phase 2 Randomized Control Trial. Diabetes Care. 2023 May 1;46(5):1060-1067. doi: 10.2337/dc22-2396.

Label	URL
A Phase 2 Study of LY3209590 in Participants With Type 2 Diabetes Mellitus	View source

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 baseline median fasting glucose and body weight 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

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 6, 2022

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 baseline median fasting glucose and body weight 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	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 of 10 units, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.
BG002	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 baseline median fasting glucose and body weight 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.
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
	BG00057.4± 9.9 BG00159.4± 9.1 BG00256.3± 8.8 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00058 BG00159 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00061 BG00159 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Argentina

Title	Measurements
	BG00029 BG00127 BG002

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.

Mean

Standard Deviation

Percentage of HbA1c

Title

Denominators

Categories

Title	Measurements
	BG0008.05± 0.77 BG001

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, Dipeptidyl peptidase IV (DPPIV) (yes/no), Sodium-glucose Cotransporter-2 (SGLT2) (yes/no), baseline body mass index (BMI) [<30, >=30]), 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 baseline median fasting glucose and body weight 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 of 10 units, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.

Units	Counts
Participants	OG000127 OG001130

Title

Denominators

Categories

Title	Measurements
	OG000-1.20± 0.076 OG001-1.26± 0.075

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	0.06			2-Sided	90	-0.11	0.24					Non-Inferiority	The non-inferiority margin is 0.4%. Non-inferiority is achieved if the upper limit of the 90% Confidence Interval is below 0.4.

Secondary

Change From Baseline in Fasting Serum Glucose

LS mean change from baseline was analysed by MMRM model with treatment, country, DPPIV (yes/no), SGLT2 (yes/no), baseline BMI [<30, >=30]), 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 baseline median fasting glucose and body weight 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 of 10 units, 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)). Rate of documented hypoglycemia per year during defined period is calculated by the number of documented hypoglycemia events within the period divided by the number of days participant at risk within the period*365.25 days.

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

Posted

Number

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 baseline median fasting glucose and body weight 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 of 10 units, 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 participants' Week 26 LY3209590 dose amount and 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 baseline median fasting glucose and body weight 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 (Affected)	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 baseline median fasting glucose and body weight 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.	0	129	6	129	18	129
EG001	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 of 10 units, during the 26-week treatment period, to achieve target fasting blood glucose of <=100 mg/dL.	1	135	4	135	19	135
EG002	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 baseline median fasting glucose and body weight 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.	0	14	1	14	8	14

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Coronary artery disease	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0011 events1 affected135 at risk EG0020 events0 affected14 at risk
Myocardial infarction	Cardiac disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0010 events0 affected135 at risk EG0020 events0 affected14 at risk
Middle ear inflammation	Ear and labyrinth disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0010 events0 affected135 at risk EG0020 events0 affected14 at risk
Covid-19 pneumonia	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0011 events1 affected135 at risk EG0020 events0 affected14 at risk
Meningitis aseptic	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0010 events0 affected135 at risk EG0020 events0 affected14 at risk
Foot fracture	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0010 events0 affected135 at risk EG0020 events0 affected14 at risk
Lipoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0010 events0 affected135 at risk EG0020 events0 affected14 at risk
Prostatic adenoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected71 at risk EG0011 events1 affected76 at risk EG0020 events0 affected5 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0010 events0 affected135 at risk EG0020 events0 affected14 at risk
Depression	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0011 events1 affected135 at risk EG0020 events0 affected14 at risk
Haematuria	Renal and urinary disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0011 events1 affected135 at risk EG0020 events0 affected14 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0010 events0 affected135 at risk EG0020 events0 affected14 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0006 events6 affected129 at risk EG0012 events2 affected135 at risk EG0021 events1 affected14 at risk
Abdominal discomfort	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Constipation	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0003 events2 affected129 at risk EG0011 events1 affected135 at risk EG0021 events1 affected14 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected129 at risk EG0018 events7 affected135 at risk EG0021 events1 affected14 at risk
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Infrequent bowel movements	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0004 events3 affected129 at risk EG0017 events7 affected135 at risk EG0020 events0 affected14 at risk
Toothache	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Chest pain	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Injection site pain	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0012 events2 affected135 at risk EG0021 events1 affected14 at risk
Fungal skin infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Mastoiditis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Urinary tract infection	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0013 events3 affected135 at risk EG0021 events1 affected14 at risk
Skin laceration	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0003 events3 affected129 at risk EG0017 events7 affected135 at risk EG0020 events0 affected14 at risk
Intervertebral disc degeneration	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Insomnia	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 events1 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Respiratory disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk
Skin odour abnormal	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0000 events0 affected129 at risk EG0010 events0 affected135 at risk EG0021 events1 affected14 at risk

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