A Phase 1b, 2-Part, Investigator- and Participant-Blind, Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of LY3532226 in Participants With Type 2 Diabetes Mellitus
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 90
- Locations
- 1
- Primary Endpoint
- Part A: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Study Overview
Brief Summary
The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY3532226 in participants with type 2 diabetes mellitus (T2DM). Blood tests will be performed to check how much LY3532226 gets into the bloodstream and how long it takes the body to eliminate it. This is a 2-part study and will last approximately 16 weeks excluding screening period for each part, respectively.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants with type 2 diabetes mellitus (T2DM) for at least 3 months before screening
- •Have the following glycosylated hemoglobin (HbA1c) levels at screening:
- •HbA1c >/= 7.0% to </= 10.0% for participants treated with diet and exercise alone and participants treated with metformin alone, and
- •HbA1c >/= 6.0% to </= 9.5% for participants treated with dipeptidyl peptidase inhibitor-4 (DPP-4) (with/without metformin) inhibitors and participants treated with metformin and sodium-glucose cotransporter-2 (SGLT-2) inhibitor
- •Participants treated with diet and exercise alone or on a stable dose of metformin for at least 3 months
- •Participants with body weight up to 150 kilograms (kg) and body mass index (BMI) of 23.0 to 45.0 kilograms per meter squared (kg/m²)
- •Male participants who agree to use effective methods of contraception and female participants not of childbearing potential
Exclusion Criteria
- •Participants who have uncontrolled diabetes defined as an episode of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to screening
- •Have a clinically significant abnormality ECG
- •Have obesity induced by other endocrine disorders such as Cushing's syndrome or Prader-Willi syndrome
- •Are on any glucose-lowering medications other than metformin, SGLT-2 inhibitors and/or DPP4
- •Have received chronic systemic glucocorticoid therapy (>2 weeks) in the past 6 months
- •Have an average weekly alcohol intake that exceeds 21 units per week (males 65 years of age or lesser) and 14 units per week (females and males 65 years of age or older)
- •Smoke more than 10 cigarettes, or cigarette equivalent, per day
Arms & Interventions
LY3532226 + Placebo (Part B)
LY3532226 administered SC in combination with placebo given SC.
Intervention: Placebo (Drug)
LY3532226 + Dulaglutide (Part A)
LY3532226 administered subcutaneously (SC) followed by dulaglutide administered SC.
Intervention: LY3532226 (Drug)
LY3532226 + Dulaglutide (Part A)
LY3532226 administered subcutaneously (SC) followed by dulaglutide administered SC.
Intervention: Dulaglutide (Drug)
Placebo + Dulaglutide (Part A)
Placebo administered SC followed by dulaglutide administered SC.
Intervention: Placebo (Drug)
Placebo + Dulaglutide (Part A)
Placebo administered SC followed by dulaglutide administered SC.
Intervention: Dulaglutide (Drug)
Dulaglutide + Placebo (Part B)
Dulaglutide administered SC in combination with placebo given SC.
Intervention: Placebo (Drug)
Dulaglutide + Placebo (Part B)
Dulaglutide administered SC in combination with placebo given SC.
Intervention: Dulaglutide (Drug)
LY3532226 + Dulaglutide (Part B)
LY3532226 administered SC in combination with Dulaglutide given SC.
Intervention: LY3532226 (Drug)
LY3532226 + Dulaglutide (Part B)
LY3532226 administered SC in combination with Dulaglutide given SC.
Intervention: Dulaglutide (Drug)
LY3532226 + Placebo (Part B)
LY3532226 administered SC in combination with placebo given SC.
Intervention: LY3532226 (Drug)
Outcomes
Primary Outcomes
Part A: Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Time Frame: Baseline up to Week 16
A summary of TEAEs and SAEs, regardless of causality, will be reported in the Reported Adverse Events module
Part B: Change from Baseline in Total Clamp Disposition Index (cDI)
Time Frame: Baseline up to Week 12
Change from Baseline in Total cDI
Secondary Outcomes
- Part A: PK: Area Under the Concentration Versus Time Curve (AUC) of LY3532226(Predose on Day 1 through Week 16)
- Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3532226(Predose on Day 1 through Week 16)
- Part B: Change from Baseline in β-cell Glucose Sensitivity (GS) from hyperglycaemic clamp(Baseline through Week 12)
- Part A & B: Change from Baseline in Glycosylated Haemoglobin (HbA1c)(Baseline through Week 16)
- Part B: Change from Baseline in Insulin Secretion Rate (ISR) from hyperglycaemic clamp(Baseline through Week 12)
- Part B: Change from Baseline in Hyperinsulinemic Euglycemic Clamp M-value(Baseline through Week 12)
- Part A & B: Change from Baseline in Fasting and Post meal Glucose during Standardized Mixed-meal Tolerance Test (sMMTT)(Baseline through Week 16)
- Part A & B: Change from Baseline in Glucagon Concentration at Fasting and Post meal during sMMTT(Baseline through Week 16)