A Study of LY4057996 in Healthy Participants and Participants With Type 1 and Type 2 Diabetes (YKAA)

Lilly

Status and phase: Enrolling; Phase 1

Conditions: Diabetes Mellitus, Type 1; Healthy; Diabetes Mellitus, Type 2

Treatments: Drug: Placebo SC; Drug: LY4057996 IV; Drug: Degludec IV; Drug: Lispro SC; Drug: Degludec SC; Drug: Placebo IV; Drug: Pre-study basal insulin SC; Drug: LY4057996 SC

Study type: Interventional

Funder types: Industry

Identifiers

NCT06945406

27329

2024-519151-28-00 (EU Trial (CTIS) Number)

J6B-MC-YKAA (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to evaluate how well LY4057996 is tolerated and what side effects may occur in healthy participants and participants with Type 1 and Type 2 Diabetes. The study drug will be administered either subcutaneously (SC) (under the skin) or intravenously (IV) (into a vein in the arm). Blood tests will be performed to check how much LY4057996 gets into the bloodstream and how long it takes the body to eliminate it.

The study will last 11 weeks for Part A1-A2, 4 weeks for A3-A5, 6 weeks for Part B and 7 weeks for Part C, all approximations, excluding a screening period.

Enrollment: 132 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Part A for Healthy Participants:

• Are overtly healthy as determined by medical evaluation, including medical history, physical exam, laboratory tests, and cardiac screening assessment

Part A for Type 2 Diabetes (T2DM) Participants:

• Are participants with T2DM diagnosed greater than 1 year before enrollment,
• On basal insulin therapy, insulin glargine, or insulin degludec, greater than 10 units per day for at least 6 months (for Cohort 5 only)
• Glycated hemoglobin (HbA1c) 6.5% to 9.5% inclusive at screening

Part B

• Have Type 1 Diabetes (T1D) for at least 1 year with a fasting C-peptide level of 0.20 nanomole per liter (nmol/L) or less or non-fasting C-peptide level of 0.30 nmol/L or less at screening
• HbA1c 6% to 8.5% inclusive at screening

Part C

• Have T1D for at least 1 year with a fasting C-peptide level of 0.20 nanomole per liter (nmol/L) or less or non-fasting C-peptide level of 0.30 nmol/L or less at screening
• HbA1c 6 to 8% inclusive at screening

All Parts

• Have blood pressure of less than 140/90 millimeters of mercury (mmHg) for healthy participants or 150/90 mmHg for participants with diabetes and pulse rate of less than 90 beats per minute (bpm) (supine)
• No hypoglycemia unawareness for all Type 1 and Type 2 Diabetes participants

Exclusion criteria

• Have had more than 1 emergency room visit or hospitalization due to poor glucose control (hyperglycemia or diabetic ketoacidosis) within 6 months prior to screening
• Have had any episodes of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia) within the 6 months prior to screening

All Parts

• Cardiovascular: no significant history of cardiovascular disease (CVD)
• Gastrointestinal: have gastroparesis or have undergone gastric surgery
• Hepatic: have acute or chronic hepatitis

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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132 participants in 6 patient groups, including a placebo group

LY4057996 Part A (Cohorts A1-A5)

Experimental group

Description:

LY4057996 administered subcutaneously (SC) and/or intravenously (IV)

Treatment:

Drug: LY4057996 SC

Drug: LY4057996 IV

Placebo Part A (Cohort A1-A5)

Placebo Comparator group

Description:

Placebo administered SC and/or IV

Treatment:

Drug: Placebo IV

Drug: Placebo SC

LY4057996 Part B

Experimental group

Description:

LY4057996 administered SC

Treatment:

Drug: LY4057996 SC

LY4057996 Part C

Experimental group

Description:

LY4057996 and interventions of pre-study basal insulin and Lispro administered SC

Treatment:

Drug: LY4057996 SC

Drug: Pre-study basal insulin SC

Drug: Lispro SC

Degludec Part A (Cohort A2-A5)

Active Comparator group

Description:

Degludec administered SC and/or IV

Treatment:

Drug: Degludec SC

Drug: Degludec IV

Degludec Part B

Active Comparator group

Description:

Degludec administered SC

Treatment:

Drug: Degludec SC