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NCT Number: NCT06280703

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

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.

Recruiting

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Key information

Age range

18 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Profil Institut für Stoffwechselforschung

Neuss, 41460, Germany

Location status: Recruiting

Location contact

Oliver Klein

PRINCIPAL_INVESTIGATOR

CONTACT

+49 (0) 2131 4018 450

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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).

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 -

  • 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, 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
  • Aspartate aminotransferase (AST) /serum glutamic oxaloacetic transaminase (SGOT) >2.5 × ULN.

Treatment and study plan

LY3938577

Drug

Administered Intravenously (IV)

Placebo

Drug

Administered Intravenously (IV)

insulin degludec

Drug

Administered Intravenously (IV)

Insulin Lispro

Drug

Administered Intravenously (IV)

Basal Insulin

Drug

Administered subcutaneously (SC)

Lispro Prandial Insulin

Drug

Administered subcutaneously (SC)

Primary outcomes

  1. 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.

    Time frame: Baseline up to Approximately Week 11

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

  2. 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.

    Time frame: Baseline up to Week 10

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

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

    Time frame: Baseline up to Approximately Week 11

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

    Time frame: Baseline up to Week 10

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

    Time frame: Baseline up to Approximately Week 11

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

    Time frame: Baseline up to Week 10

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

    Time frame: Predose on day 1 up to week 13 post dose

    PK: AUC of LY3938577 for intravenous administration

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

    Time frame: Predose on day 1 up to week 13 post dose

    PK: AUC of LY3938577 for SC administration

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

    Time frame: Predose on day 1 up to week 13 post dose

    PK: AUC of LY3938577

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

    Time frame: Predose on day 1 up to week 13 post dose

    PK: AUC of LY3938577 for SC administration

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

    Time frame: Predose on day 1 up to week 13 post dose

    PK: AUC of LY3938577 for SC administration

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

    Time frame: Predose on day 1 up to week 13 post dose

    PK: Cmax of LY3938577

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

    Time frame: Predose on day 1 up to week 13 post dose

    PK: Cmax of LY3938577

  14. Part C: PK: Concentration of LY3938577

    Time frame: Predose on day 1 up to week 13 post dose

Secondary outcomes

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

    Time frame: Predose up to day 14 post dose

    Measured at different glucose levels in participants with T1DM

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

    Time frame: Predose up to day 14 post dose

    Measured at different glucose levels in participants with T1DM

Study contacts

Contact information is provided by the study sponsor or research team.

Physicians interested in becoming principal investigators please contact

CONTACT

[email protected]

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

CONTACT

[email protected]

1-317-615-4559

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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

Important dates

Study start
2024
Primary completion
2026
Study completion
2026
First posted
Feb 28, 2024
Registry last updated
Jan 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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