Clinical trial NCT06280703: A Study of LY3938577 in Healthy Participants and Participants With Type 1 Diabetes Mellitus (T1DM)
Official title: 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 LY3938577 in Healthy Participants and Participants With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Healthy
Type 1 Diabetes Mellitus
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-02-28
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Parallel (Part A) and Crossover design (Part B and Part C)
Primary purpose: BASIC_SCIENCE

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 three parts (A, B, and C). 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.

The study will last up to approximately 11 weeks for Part A, 10 weeks for Part B, and 13 weeks for Part C including screening period.


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).

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:

  * 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.

Primary outcomes:
measure: 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.
timeFrame: Baseline up to Approximately Week 11
measure: 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.
timeFrame: Baseline up to Week 10
measure: Part A: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Baseline up to Approximately Week 11
measure: Part B: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: Baseline up to Week 10
measure: Part A: Number of Participants With Clinically Significant Changes in Safety Laboratory Parameters
timeFrame: Baseline up to Approximately Week 11
measure: Part B: Number of Participants With Clinically Significant Changes in Safety Laboratory Parameters
timeFrame: Baseline up to Week 10
measure: Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577
timeFrame: Predose on day 1 up to week 13 post dose
measure: Part A: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577
timeFrame: Predose on day 1 up to week 13 post dose
measure: Part B: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577
timeFrame: Predose on day 1 up to week 13 post dose
measure: Part C: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577
timeFrame: Predose on day 1 up to week 13 post dose
measure: Part A: PK: Maximum Observed Concentration (Cmax) of LY3938577
timeFrame: Predose on day 1 up to week 13 post dose
measure: Part B: PK: Maximum Observed Concentration (Cmax) of LY3938577
timeFrame: Predose on day 1 up to week 13 post dose
measure: Part C: PK: Concentration of LY3938577
timeFrame: Predose on day 1 up to week 13 post dose
Secondary outcomes:
measure: Part B: Pharmacodynamic (PD): Area under the glucose infusion rate curve (GIR AUC) of LY3938577
timeFrame: Predose up to day 14 post dose
measure: Part C: PD: Glucose infusion rate (GIR) of LY3938577
timeFrame: Predose up to day 14 post dose
Other outcomes:
Locations:
city: Neuss
country: Germany
facility: Profil Institut für Stoffwechselforschung
state: Nordrhein-Westfalen
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: