Evaluating LY3938577 in Healthy Individuals and Those with Type 1 Diabetes

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

This study is testing a new drug called LY3938577 to see how it works in healthy people and those with Type 1 Diabetes, focusing on how well it lowers blood sugar compared to insulin.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 118 (estimated)
• Ages: 18 Years to 64 Years
• Sex: All
• Sponsor: Eli Lilly and Company (Industry-sponsored)
• Locations: 1 site (Neuss)
• Trial ID: NCT06280703 on ClinicalTrials.gov

What this trial studies

This study investigates the pharmacokinetics of LY3938577, a new drug, in healthy participants and individuals with Type 1 Diabetes Mellitus (T1DM). It consists of three parts: Part A assesses the drug's absorption and elimination in healthy subjects, while Parts B and C evaluate its blood sugar-lowering effects compared to Insulin Degludec in T1DM patients. Safety and tolerability will also be monitored throughout the study, with participants receiving either LY3938577 or placebo via intravenous or subcutaneous administration.

Who should consider this trial

Good fit: Ideal candidates include healthy individuals and those with Type 1 Diabetes Mellitus who meet specific inclusion criteria regarding their health status and diabetes management.

Not a fit: Patients with poorly controlled diabetes or significant recent health issues may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to a new treatment option for managing blood sugar levels in individuals with Type 1 Diabetes.

How similar studies have performed: While this approach is novel, similar studies have shown promise in evaluating new diabetes treatments.

Eligibility criteria

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.

Where this trial is running

Neuss

• Profil Institut für Stoffwechselforschung — Neuss, Germany (Recruiting)

Study contacts

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

Conditions Healthy; Type 1 Diabetes Mellitus