Clinical trial NCT06945406: A Study of LY4057996 in Healthy Participants and Participants With Type 1 and Type 2 Diabetes
Official title: A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY4057996 in Healthy Participants and Participants With Type 1 and Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy
Diabetes Mellitus, Type 1
Diabetes Mellitus, Type 2
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2025-04-25
Enrollment: 132
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Parts A and C are sequential, Part B is crossover
Primary purpose: BASIC_SCIENCE

Brief summary: 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, 5 weeks for Part B and 7 weeks for Part C, all approximations, excluding a screening period.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with One or More Serious Adverse Event(s) (SAEs) and Adverse Event(s) (AEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline to Study Completion (Up to 47 Weeks)
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY4057996
timeFrame: Baseline to Study Completion (Up to 47 Weeks)
measure: PK: Maximum Concentration (Cmax) of LY4057996
timeFrame: Baseline to Study Completion (Up to 47 Weeks)
measure: Pharmacodynamic (PD): Change from Baseline in Fasting Glucose
timeFrame: Baseline to Study Completion (Up to 47 Weeks)
measure: PD: AUC of Glucose Infusion Rate (GIR)
timeFrame: Baseline Up to 10 weeks
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung
state: Nordrhein-Westfalen
Study officials:
affiliation: Eli Lilly and Company
name: Contact Lilly at 1-800-LillyRx (1-800-545-5979)
role: STUDY_DIRECTOR
References: