A Study of LY3457263 in Healthy Participants and Participants With Type 2 Diabetes

A Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3457263 in Healthy Participants and in Patients With Type 2 Diabetes

The main purpose of this study is to investigate the safety and tolerability of the study drug LY3457263 in healthy participants and participants with type 2 diabetes. Blood tests will be performed to investigate how the body processes the study drug and how the study drug affects the body. The study has two parts (part A and B). Each part will last up to 10 weeks and may include up to either 13 (part A) or 19 (part B) visits.

Study Overview

• Status: Completed
• Conditions: Healthy; Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Dulaglutide; Drug: LY3457263

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Mainz, Germany, 55116
    • Profil Mainz
  • Nordrhein-Westfalen
    • Neuss, Nordrhein-Westfalen, Germany, 41460
      • Profil Institut für Stoffwechselforschung

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males that agree to use an effective method of contraception or agree to remain abstinent
• Females that are not of childbearing potential due to postmenopausal status or due to surgical sterility

• Part A only:

  • Are overtly healthy
  • Body mass index (BMI) of 18.5 to 35 kilograms per meter squared (kg/m²)

• Part B only:

  • Have been diagnosed with Type 2 Diabetes (T2D) for at least 6 months prior to screening
  • Be treated for T2D with stable dose of metformin, a stable dose of a dipeptidyl peptidase-4 (DPP-4) inhibitor with or without metformin, or a stable dose of a glucagon-like peptide-1 (GLP-1) receptor agonist with or without metformin for at least 3 months prior to screening
  • BMI of 27 to 40 kg/m²

Exclusion Criteria:

• Have undergone any form of bariatric surgery

  • Have used or intend to use medications that promote weight loss within 3 months prior to screening, for the duration of the study

  • Part A only:

    • Have fasting plasma glucose (PG) levels ≥7 millimoles per liter (mmol/L) (≥126 milligrams per deciliter (mg/dL)) at screening
    • Have Hemoglobin A1c (HbA1c) level ≥ 6.5% (48 millimoles per mole (mmol/mol)) at screening
    • Have serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >20% and 10%, above the upper limit of normal (ULN), respectively. Elevation of total bilirubin level is considered acceptable in case of Gilbert's disease (with a normal direct bilirubin)

  • Part B only:

    • Have Type 1 Diabetes or latent autoimmune diabetes in adults
    • Have uncontrolled diabetes defined as an episode of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to screening
    • Have known proliferative diabetic retinopathy, diabetic maculopathy, or severe nonproliferative diabetic retinopathy
    • Present comorbid conditions commonly associated with diabetes (for example, hypertension, hypercholesterolemia, hypothyroidism) unless they are well-controlled with stable medication
    • Have had an episode of severe hypoglycaemia within 6 months prior to screening, or have a history of hypoglycaemia unawareness or poor recognition of hypoglycaemia
    • Have a history of acute or chronic pancreatitis or elevation in serum lipase and/or amylase >2 × ULN at screening
    • Have a resting heart rate of <50 or >100 beats per minute
    • Have an estimated glomerular filtration rate (<60 milliliter/minute (mL/min)/1.73 m2, or a level of estimated glomerular filtration rate that would contraindicate the use of metformin per the label in the respective country
    • Have a screening calcitonin ≥20.0 picograms per milliliter (pg/mL)
    • Fasting serum triglyceride level of >500 mg/dL at screening
    • Have serum AST or ALT >3 × ULN or TBL >1.5 × ULN (except for participants diagnosed with Gilbert's syndrome)
    • Have taken any prescription medication that are specifically indicated for lowering serum triglycerides within the last 3 months
    • Have taken within the last 3 months any medications that interfere with absorption of dietary cholesterol or fats
    • Use of medications known to prolong the QT/QTc interval
    • Treated only with diet and exercise at study entry

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3457263 - Part A; Escalating single doses of LY3457263 administered subcutaneously (SC) to healthy participants	Drug: LY3457263; Administered SC
Placebo Comparator: Placebo - Part A; Placebo administered SC to healthy participants	Drug: Placebo; Administered SC
Experimental: LY3457263 - Part B; Escalating single doses of LY3457263 administered SC in combination with Dulaglutide administered SC to participants with type 2 diabetes	Drug: Dulaglutide; Administered SC; Other Names: LY2189265; Drug: LY3457263; Administered SC
Placebo Comparator: Placebo - Part B; Placebo administered SC in combination with Dulaglutide administered SC to participants with type 2 diabetes	Drug: Placebo; Administered SC; Drug: Dulaglutide; Administered SC; Other Names: LY2189265

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module	Baseline through Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3457263	PK: AUC[0-inf] of LY3457263	Day 1 through Day 42

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Actual): December 21, 2021
• Study Completion (Actual): December 21, 2021

Study Registration Dates

• First Submitted: November 20, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (Actual): November 23, 2020

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: January 1, 2022

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; Dulaglutide
• Other Study ID Numbers: 17261; 2020-001828-34 (EudraCT Number); J1R-MC-GZFA (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.: No