A Study of LY3532226 in Participants With Type 2 Diabetes Mellitus

Phase 1

Completed

• Conditions: Diabetes Mellitus, Type 2
• Interventions: Drug: LY3532226; Drug: Placebo; Drug: Dulaglutide

• Registration Number: NCT05407961
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-05-26
• Study First Submitted QC: 2022-06-03
• Study Start: 2022-06-07
• Study First Posted: 2022-06-07
• Primary Completion: 2024-01-12
• Study Completion: 2024-01-12
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-28
• Last Update Posted: 2024-03-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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:

  1. HbA1c >/= 7.0% to </= 10.0% for participants treated with diet and exercise alone and participants treated with metformin alone, and
  2. 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LY3532226 + Placebo (Part B)	LY3532226	LY3532226 administered SC in combination with placebo given SC.
LY3532226 + Placebo (Part B)	Placebo	LY3532226 administered SC in combination with placebo given SC.
LY3532226 + Dulaglutide (Part A)	Dulaglutide	LY3532226 administered subcutaneously (SC) followed by dulaglutide administered SC.
Placebo + Dulaglutide (Part A)	Placebo	Placebo administered SC followed by dulaglutide administered SC.
Placebo + Dulaglutide (Part A)	Dulaglutide	Placebo administered SC followed by dulaglutide administered SC.
LY3532226 + Dulaglutide (Part B)	Dulaglutide	LY3532226 administered SC in combination with Dulaglutide given SC.
Dulaglutide + Placebo (Part B)	Dulaglutide	Dulaglutide administered SC in combination with placebo given SC.
LY3532226 + Dulaglutide (Part B)	LY3532226	LY3532226 administered SC in combination with Dulaglutide given SC.
Dulaglutide + Placebo (Part B)	Placebo	Dulaglutide administered SC in combination with placebo given SC.
LY3532226 + Dulaglutide (Part A)	LY3532226	LY3532226 administered subcutaneously (SC) followed by dulaglutide administered SC.

Primary Outcome Measures

Name	Time	Method
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	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)	Baseline up to Week 12	Change from Baseline in Total cDI

Secondary Outcome Measures

Name	Time	Method
Part A: PK: Area Under the Concentration Versus Time Curve (AUC) of LY3532226	Predose on Day 1 through Week 16	PK: AUC of LY3532226
Part A: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3532226	Predose on Day 1 through Week 16	PK: Cmax of LY3532226
Part B: Change from Baseline in β-cell Glucose Sensitivity (GS) from hyperglycaemic clamp	Baseline through Week 12	Change from Baseline in β-cell GS from hyperglycaemic clamp
Part A & B: Change from Baseline in Glycosylated Haemoglobin (HbA1c)	Baseline through Week 16	Change from Baseline in HbA1c
Part B: Change from Baseline in Insulin Secretion Rate (ISR) from hyperglycaemic clamp	Baseline through Week 12	Change from Baseline in ISR from hyperglycaemic clamp
Part B: Change from Baseline in Hyperinsulinemic Euglycemic Clamp M-value	Baseline through Week 12	Change from Baseline in Hyperinsulinemic Euglycemic Clamp M-value
Part A & B: Change from Baseline in Fasting and Post meal Glucose during Standardized Mixed-meal Tolerance Test (sMMTT)	Baseline through Week 16	Change from Baseline in Fasting and Post meal Glucose during sMMTT
Part A & B: Change from Baseline in Glucagon Concentration at Fasting and Post meal during sMMTT	Baseline through Week 16	Change from Baseline in Glucagon Concentration at Fasting and Post meal during sMMTT

Trial Locations

Locations (1)

Profil Institut für Stoffwechselforschung; 🇩🇪 Neuss, Germany