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

A Three-Part, Randomized, Double-Blind (Part A) and Open-Label (Part B and Part C), Multi-Dose, Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous LY3938577 in Healthy Participants and Participants With Type 1 Diabetes Mellitus

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 three parts (A, B, and C). Healthy participants in part A will receive one single dose of LY3938577 or a placebo, whereas participants in Parts B and C with T1DM will receive single doses of either LY3938577 or Insulin Deglude given via intravenous (IV) infusion.

The study will last up to approximately 5.5, 10 and 13 weeks for parts A, B, and C, respectively, including screening period.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy; Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: LY3938577; Drug: Placebo; Drug: Insulin Lispro; Drug: Insulin Degludec

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: This is a single site clinical trial. 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: ClinicalTrials.gov@Lilly.com

Study Locations

• Germany
  • Nordrhein-Westfalen
    • Neuss, Nordrhein-Westfalen, Germany, 41460
      • Profil Institut für Stoffwechselforschung
      • Principal Investigator: Oliver Klein
      • Contact: Phone Number: +49 (0) 2131 4018 450

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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).

All Parts -

• Have normal blood pressure, pulse rate and safety laboratory test results that are acceptable for the study.
• Have body mass index (BMI) between 18.0 and 35.0 kilograms per meter squared (kg/m²), inclusive, at screening.
• Have venous access sufficient to allow for blood sampling.
• Male and/or female not of childbearing potential.

Exclusion Criteria:

Parts B and C -

• 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.
• Have been treated with Glucagon-like Peptide-1 Receptor Agonists (GLP1-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.

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:

  • TBL >2 × the Upper Limit of Normal (ULN) in the absence of Gilbert's syndrome, or
  • ALT/serum glutamic pyruvic transaminase (SGPT) >2.5 × ULN, or
  • AST/serum glutamic oxaloacetic transaminase (SGOT) >2.5 × ULN.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: LY3938577; Single dose of LY3938577 administered intravenously (IV) in healthy participants.	Drug: LY3938577; Administered Intravenously (IV)
Placebo Comparator: Part A: Placebo; Single dose of Placebo administered intravenously (IV) in healthy participants.	Drug: Placebo; Administered Intravenously (IV)
Experimental: Part B: LY3938577; For each euglycemic and hyperglycemic clamps participants with T1DM will receive single doses of LY3938577 administered intravenously (IV) 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; Administered Intravenously (IV); Drug: Insulin Lispro; Administered Intravenously (IV)
Active Comparator: Part B : Insulin Degludec; For each euglycemic and hyperglycemic clamps participants with T1DM will receive single doses of Insulin Degludec administered intravenously (IV) 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 Lispro; Administered Intravenously (IV); Drug: Insulin Degludec; Administered Intravenously (IV)
Experimental: Part C: LY3938577; During 3-step clamp and a hyperglycemic clamp with hypoglycemia provocation participants with T1DM will receive LY3938577 by continuous infusion. Insulin Lispro will be administered intravenously to maintain a stable glucose level before administration of LY3938577.	Drug: LY3938577; Administered Intravenously (IV); Drug: Insulin Lispro; Administered Intravenously (IV)
Active Comparator: Part C: Insulin Degludec; During 3-step clamp and a hyperglycemic clamp with hypoglycemia provocation participants with T1DM will receive Insulin Degludec by continuous infusion. Insulin Lispro will be administered intravenously to maintain a stable glucose level before administration of Insulin Degludec.	Drug: Insulin Lispro; Administered Intravenously (IV); Drug: Insulin Degludec; Administered Intravenously (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Week 5.5
Part B: 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 Week 5.5
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 Week 5.5
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	Predose on day 1 up to day 8 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 day 14 post dose
Part A: PK: Maximum Observed Concentration (Cmax) of LY3938577	PK: Cmax of LY3938577	Predose on day 1 up to day 8 post dose
Part B: PK: Maximum Observed Concentration (Cmax) of LY3938577	PK: Cmax of LY3938577	Predose on day 1 up to day 14 post dose
Part C: PK: Concentration of LY3938577		Predose on day 1 up to day 14 post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B: Pharmacodynamic (PD): Area under the glucose infusion rate curve (GIR AUC) of LY3938577	Measured at different glucose levels in participants with T1DM	Predose up to day 14 post dose
Part C: PD: Glucose infusion rate (GIR) of LY3938577	Measured at different glucose levels in participants with T1DM	Predose up to day 14 post dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Estimated): May 15, 2024
• Primary Completion (Estimated): February 17, 2025
• Study Completion (Estimated): February 17, 2025

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: February 20, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 3, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Lispro
• Other Study ID Numbers: 18792; J4P-MC-IYAB (Other Identifier: Eli Lilly and Company); U1111-1301-8386 (Other Identifier: Universal Trial Number); 2023-510365-10-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes