A Study of LY3938577 in Healthy Participants and Participants With Type 1 Diabetes Mellitus (T1DM)

NCT06280703 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: 18792J4P-MC-IYABU1111-1301-83862023-510365-10-00
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief Summary

The main purpose of this study is to look at the amount of the study drug LY3938577 that gets into the blood stream and how long it takes the body to get rid of it. At a later stage of this study (part B and C) the blood sugar lowering effect and the duration of action of LY3938577 will be evaluated compared to Insulin Degludec. The study will also evaluate the safety and tolerability of LY3938577 and information about any side effects experienced will be collected. The study will be conducted in four parts (A, B, C, and D). Healthy participants in Part A Period 1 will receive a single dose of LY3938577 or a placebo given via intravenous (IV) infusion. In Part A Period 2, participants will receive a single subcutaneous (SC) dose of either LY3938577 or placebo. Participants in Part B with Type 1 Diabetes Mellitus (T1DM) will receive single doses of either LY3938577 or Insulin Degludec given via IV infusion. Participants in Part C with Type 1 Diabetes Mellitus (T1DM) will receive two doses of either LY3938577 or Insulin Degludec administered SC. Participants in Part D with Type 1 Diabetes Mellitus (T1DM) will be evaluated in 2 periods, with Period 1 administered pre-study basal insulin and lispro mealtime insulin to establish insulin needs, and Period 2 administered lispro mealtime insulin and daily doses of LY3938577. The study will last up to approximately 11 weeks for Part A, 10 weeks for Part B, 13 weeks for Part C, and 10 weeks for Part D , including screening period.

Conditions

Healthy; Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (14)

• Part A: Number of participants with one or more Adverse Event (s) (AEs), and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration.

  A summary of AEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.

  Baseline up to Approximately Week 11

• Part B and D: Number of participants with one or more Adverse Event (s) (AEs), and Serious Adverse Event(s) (SAEs) considered by the investigator to be related to study drug administration.

  A summary of AEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.

  Baseline up to Week 10

• Part A: Number of Participants With Clinically Significant Changes in Vital Signs

  Baseline up to Approximately Week 11

• Part B: Number of Participants With Clinically Significant Changes in Vital Signs

  Baseline up to Week 10

• Part A: Number of Participants With Clinically Significant Changes in Safety Laboratory Parameters

  Baseline up to Approximately Week 11

• Part B: Number of Participants With Clinically Significant Changes in Safety Laboratory Parameters

  Baseline up to Week 10

• Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577

  PK: AUC of LY3938577 for intravenous administration

  Predose on day 1 up to week 13 post dose

• Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577

  PK: AUC of LY3938577 for SC administration

  Predose on day 1 up to week 13 post dose

• Part B: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577

  PK: AUC of LY3938577

  Predose on day 1 up to week 13 post dose

• Part C: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577

  PK: AUC of LY3938577 for SC administration

  Predose on day 1 up to week 13 post dose

• Part D: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577

  PK: AUC of LY3938577 for SC administration

  Predose on day 1 up to week 13 post dose

• Part A: PK: Maximum Observed Concentration (Cmax) of LY3938577

  PK: Cmax of LY3938577

  Predose on day 1 up to week 13 post dose

• Part B: PK: Maximum Observed Concentration (Cmax) of LY3938577

  PK: Cmax of LY3938577

  Predose on day 1 up to week 13 post dose

• Part C: PK: Concentration of LY3938577

  Predose on day 1 up to week 13 post dose

Secondary Outcomes (2)

• Part B: Pharmacodynamic (PD): Area under the glucose infusion rate curve (GIR AUC) of LY3938577

  Predose up to day 14 post dose

• Part C: PD: Glucose infusion rate (GIR) of LY3938577

  Predose up to day 14 post dose

Study Arms (10)

Part A Period 1: LY3938577

EXPERIMENTAL

Single dose of LY3938577 administered intravenously (IV) in healthy participants.

Drug: LY3938577

Part A Period 1: Placebo

PLACEBO COMPARATOR

Single dose of Placebo administered intravenously (IV) in healthy participants.

Drug: Placebo

Part B: LY3938577

EXPERIMENTAL

For each euglycemic and hyperglycemic clamps participants with T1DM will receive single doses of LY3938577 administered intravenously with Insulin Lispro administered at a constant low rate to cover individual participant's basal (fasting) insulin demand to maintain a stable glucose level.

Drug: LY3938577; Drug: Insulin Lispro

Part B: Insulin Degludec

ACTIVE COMPARATOR

For each euglycemic and hyperglycemic clamps participants with T1DM will receive single doses of Insulin Degludec administered intravenously with Insulin Lispro administered at a constant low rate to cover individual participant's basal (fasting) insulin demand to maintain a stable glucose level.

Drug: Insulin Degludec; Drug: Insulin Lispro

Part C: LY3938577

EXPERIMENTAL

LY3938577 administered subcutaneously (SC)

Drug: LY3938577

Part C: Insulin Degludec

ACTIVE COMPARATOR

Insulin Degludec administered subcutaneously (SC)

Drug: Insulin Degludec

Part A Period 2: LY3938577

EXPERIMENTAL

Sequential dose of LY3938577 administered subcutaneously (SC).

Drug: LY3938577

Part A Period 2: Placebo

PLACEBO COMPARATOR

Sequential dose of Placebo administered subcutaneously (SC)

Drug: Placebo

Part D Period 1: Basal Insulin and Lispro Prandial Insulin

OTHER

Pre-study basal insulin (provided by patient) and lispro prandial insulin administered SC

Drug: Basal Insulin; Drug: Lispro Prandial Insulin

Part D Period 2: Lispro Prandial Insulin and LY3938577

EXPERIMENTAL

Lispro prandial insulin and LY3938577 administered SC

Drug: LY3938577; Drug: Lispro Prandial Insulin

Interventions

LY3938577 DRUG

Administered Intravenously (IV)

Part A Period 1: LY3938577; Part B: LY3938577

Placebo DRUG

Administered Intravenously (IV)

Part A Period 1: Placebo

Insulin Lispro DRUG

Administered Intravenously (IV)

Part B: Insulin Degludec; Part B: LY3938577

Basal Insulin DRUG

Administered subcutaneously (SC)

Part D Period 1: Basal Insulin and Lispro Prandial Insulin

Lispro Prandial Insulin DRUG

Administered subcutaneously (SC)

Part D Period 1: Basal Insulin and Lispro Prandial Insulin; Part D Period 2: Lispro Prandial Insulin and LY3938577

Insulin Degludec DRUG

Administered Intravenously (IV)

Part B: Insulin Degludec

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Part A -
• Participants who are overtly healthy as determined by medical history and physical examination.
• Parts B and C -
• Have Type 1 Diabetes Mellitus (T1DM) for at least 2 years with a fasting C-peptide level of 0.20 Nanomoles Per Liter (nmol/L) or less, or nonfasting C-peptide level of 0.30 nmol/L or less at screening.
• Have well-controlled HbA1c between 6.0% to 8.5 percent (%).
• Insulin pump users with a total daily basal dose between 15 to 45 International Unit (IU).
• Part D -
• Have T1DM for at least 1 year with a fasting C-peptide level of 0.20 nmol/L or less, or non-fasting C-peptide level of 0.30 nmol/L or less.
• HbA1c between 6% to 8.5% inclusive.
• Insulin pump users with a total daily basal dose between 15 to 45 International Unit (IU).
• Insulin multiple daily injection users (glargine or degludec insulin) with a total daily insulin dose between 0.3 to \<1.2 (I)U/kg/day.
• No hypoglycaemia unawareness.
• Basal insulin dose that is between 30% to 70% of the total daily insulin dose
• Are able to complete the exercise challenge test.
• All Parts -

You may not qualify if:

• Parts B, C, and D -
• Have had more than 1 emergency room visit or hospitalization due to poor glucose control (hyperglycemia or diabetic ketoacidosis) within the last 6 months prior to screening.
• Have had any episodes of severe hypoglycemia (defined as requiring assistance due to neurologically disabling hypoglycemia), hypoglycemia unawareness, or both within the last 6 months prior to screening.
• Parts B and C -
• Have been treated with Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RA), Dipeptidyl Peptidase 4 (DPP4) inhibitor, Glucose-dependent Insulinotropic Polypeptide (GIP) agonists, Metformin, or Sodium-Glucose Transport Protein 2 (SGLT2) inhibitors within the previous 3 months.
• Have received systemic or inhaled glucocorticoid therapy (excluding topical, intraarticular, and intraocular preparations) for more than 14 consecutive days within 4 weeks before screening.
• Part D -
• Have been treated with Dipeptidyl peptidase-4 (DPP-IV) inhibitors, GLP-1 RA, GIP/GLP-1 RA, Metformin, Pramlintide, SGLT2 inhibitors, or Neutral Protamine Hagedorn (NPH) insulin within the previous 3 months.
• All Parts -
• Have had any of the following cardiovascular conditions: acute myocardial infarction, New York Heart Association Class III or IV heart failure, or cerebrovascular accident (stroke).
• Have gastroparesis or have undergone gastric bypass (bariatric) surgery or restrictive bariatric surgery (for example, Lap-Band®) prior to screening.
• Have history of renal transplantation, currently receiving renal dialysis, have serum creatinine level of more than 2.00 milligrams per decilitre (mg/dL) or have an estimated glomerular filtration rate of less than 60.0 milliliters (mL) / minute /1.73 square meters.
• Have acute or chronic hepatitis, or obvious clinical signs or symptoms of any other liver disease except non-alcoholic fatty liver disease (that is, participants with non-alcoholic fatty liver disease are eligible for participation), and/or have elevated liver enzyme measurements, as determined by the local laboratory at screening and as indicated:
• Total bilirubin (TBL) \>2 × the Upper Limit of Normal (ULN) in the absence of Gilbert's syndrome, or
• Alanine aminotransferase (ALT) /serum glutamic pyruvic transaminase (SGPT) \>2.5 × ULN, or

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Profil Institut für Stoffwechselforschung

Neuss, 41460, Germany

RECRUITING

Related Links

• A Study of LY3938577 in Healthy Participants and Participants With Type 1 Diabetes Mellitus (T1DM)

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

insulin degludec; Insulin Lispro

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double (Participant, Investigator) Double-Blind (Part A) and Open-Label (Part B, Part C, and Part D)
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Crossover Assignment Parallel (Part A) and Crossover design (Part B, Part C, and Part D)

Study Record Dates

• First Submitted: February 20, 2024
• First Posted: February 28, 2024
• Study Start: May 15, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)