A Study of LY3532226 in Participants With Type 2 Diabetes Mellitus

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

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 Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Placebo; Drug: Dulaglutide; Drug: LY3532226

• Study Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: This is a single site clinical trial. 1-877-CTLILLY (1-877-285-4559) or; Phone Number: 1-317-615-4559; Email: ClinicalTrials.gov@Lilly.com

Study Locations

• Germany
  • Neuss, Germany, 41460
    • Profil Institut für Stoffwechselforschung

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3532226 + Dulaglutide (Part A); LY3532226 administered subcutaneously (SC) followed by dulaglutide administered SC.	Drug: Dulaglutide; Administered SC.; Other Names: Trulicity; Drug: LY3532226; Administered SC.
Placebo Comparator: Placebo + Dulaglutide (Part A); Placebo administered SC followed by dulaglutide administered SC.	Drug: Placebo; Administered SC.; Drug: Dulaglutide; Administered SC.; Other Names: Trulicity
Active Comparator: Dulaglutide + Placebo (Part B); Dulaglutide administered SC in combination with placebo given SC.	Drug: Placebo; Administered SC.; Drug: Dulaglutide; Administered SC.; Other Names: Trulicity
Experimental: LY3532226 + Dulaglutide (Part B); LY3532226 administered SC in combination with Dulaglutide given SC.	Drug: Dulaglutide; Administered SC.; Other Names: Trulicity; Drug: LY3532226; Administered SC.
Experimental: LY3532226 + Placebo (Part B); LY3532226 administered SC in combination with placebo given SC.	Drug: Placebo; Administered SC.; Drug: LY3532226; Administered SC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	A summary of TEAEs and SAEs, regardless of causality, will be reported in the Reported Adverse Events module	Baseline up to Week 16
Part B: Change from Baseline in Total Clamp Disposition Index (cDI)	Change from Baseline in Total cDI	Baseline up to Week 12

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Actual): January 12, 2024
• Study Completion (Actual): January 12, 2024

Study Registration Dates

• First Submitted: May 26, 2022
• First Submitted That Met QC Criteria: June 3, 2022
• First Posted (Actual): June 7, 2022

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Glucagon-Like Peptide-1 Receptor Agonists; Dulaglutide
• Other Study ID Numbers: 17835; 2021-003257-31 (EudraCT Number); J2V-MC-GZLB (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes