A Study of LY3938577 in Healthy Participants and Participants With Type 1 Diabetes Mellitus (T1DM)
- Conditions
- HealthyType 1 Diabetes Mellitus
- Interventions
- Registration Number
- NCT06280703
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 70
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Part A Period 1: LY3938577 LY3938577 Single dose of LY3938577 administered intravenously (IV) in healthy participants. Part A Period 1: Placebo Placebo Single dose of Placebo administered intravenously (IV) in healthy participants. Part B: LY3938577 LY3938577 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. Part B: LY3938577 Insulin Lispro 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. Part A Period 2: Placebo Placebo Sequential dose of Placebo administered subcutaneously (SC) Part B : Insulin Degludec insulin degludec 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. Part B : Insulin Degludec Insulin Lispro 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. Part C: LY3938577 LY3938577 LY3938577 administered subcutaneously (SC) Part C: Insulin Degludec insulin degludec Insulin Degludec administered subcutaneously (SC) Part A Period 2: LY3938577 LY3938577 Sequential dose of LY3938577 administered subcutaneously (SC).
- Primary Outcome Measures
Name Time Method 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. 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.
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. 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.
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 Predose on day 1 up to week 13 post dose PK: AUC of LY3938577 for SC administration
Part B: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577 Predose on day 1 up to week 13 post dose PK: AUC of LY3938577
Part C: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3938577 Predose on day 1 up to week 13 post dose PK: AUC of for SC administration LY3938577
Part A: PK: Maximum Observed Concentration (Cmax) of LY3938577 Predose on day 1 up to week 13 post dose PK: Cmax of LY3938577
Part B: PK: Maximum Observed Concentration (Cmax) of LY3938577 Predose on day 1 up to week 13 post dose PK: Cmax of LY3938577
Part C: PK: Concentration of LY3938577 Predose on day 1 up to week 13 post dose
- Secondary Outcome Measures
Name Time Method Part B: Pharmacodynamic (PD): Area under the glucose infusion rate curve (GIR AUC) of LY3938577 Predose up to day 14 post dose Measured at different glucose levels in participants with T1DM
Part C: PD: Glucose infusion rate (GIR) of LY3938577 Predose up to day 14 post dose Measured at different glucose levels in participants with T1DM
Related Research Topics
Explore scientific publications, clinical data analysis, treatment approaches, and expert-compiled information related to the mechanisms and outcomes of this trial. Click any topic for comprehensive research insights.
Trial Locations
- Locations (1)
Profil Institut für Stoffwechselforschung
🇩🇪Neuss, Nordrhein-Westfalen, Germany