A Study of LY3540378 in Healthy Participants

A Single and Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY3540378 in Healthy Participants

The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY3540378 in healthy participants following single and multiple doses (Parts A and B) and multiple doses in Japanese (Part C) and Chinese (Part D) healthy participants. Blood tests will be performed to check how much LY3540378 gets into the bloodstream and how long it takes the body to eliminate it. This is a 4-part study and may last up to 70, 113, 113 and 113 days for each participant in Parts A, B, C, and D respectively.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: LY3540378; Drug: LY3540378

• Study Type: Interventional
• Enrollment (Actual): 134
• Phase: Phase 1

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 138623
    • Lilly Centre for Clinical Pharmacology
• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Overtly healthy males or females, as determined by medical history and physical examination.
• Body mass index (BMI) within the range of 19 to 30 kilograms per meter squared (kg/m²)
• For Part C, participants should be first generation Japanese origin.
• For Part D, participants should be first generation Chinese origin.
• Male participants must agree to adhere to contraception restrictions and female participants not of childbearing potential and may include who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, or tubal ligation), or congenital anomaly such as müllerian agenesis or postmenopausal

Exclusion Criteria:

• Participants with troponin I results above the upper reference limit judged to be clinically significant by the investigator
• Diagnosed with orthostatic hypotension defined as a decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within 3 minutes of standing when compared with blood pressure from the sitting or supine position.
• Have a significant history of or current cardiovascular (for example, myocardial infarction, congestive HF, cerebrovascular accident, venous thromboembolism, etc.), respiratory, renal, gastrointestinal, endocrine, haematological (including history of thrombocytopenia), or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs
• Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis biliary and pancreatic disorder
• Have evidence of significant active neuropsychiatric disease as determined by the investigator
• Have received chronic (lasting >14 consecutive days) systemic glucocorticoid therapy in the past year, or have received any glucocorticoid therapy within 1 month before screening
• Have an abnormality in the 12-lead ECG
• Have serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2 × the upper limit of normal (ULN) or total bilirubin (TBL) >1.5 × ULN
• Have a history of acute or chronic pancreatitis or elevation in serum lipase and/or amylase greater than 1.5 × ULN
• Have known allergies to LY3540378 or related compounds
• Have donated blood of >450 mL, or have participated in a clinical study that required similar blood volume drawn within the past 30 calendar days
• Have an average weekly alcohol intake that exceeds 7 units per week, or are unwilling to stop alcohol consumption as required during the study (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)
• Smoke >10 cigarettes per day or the equivalent, or are unable or unwilling to refrain from nicotine
• Allergy to iodine (shellfish allergy)
• Have a history of sensitivity to lithium carbonate

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3540378 (Part A); Single ascending doses of LY3540378 administered either intravenously (IV) or subcutaneously (SC).	Drug: LY3540378; Administered IV or SC.; Drug: LY3540378; Administered SC.
Experimental: LY3540378 (Part B); Multiple ascending doses of LY3540378 administered SC.	Drug: LY3540378; Administered IV or SC.; Drug: LY3540378; Administered SC.
Experimental: LY3540378 (Part C); Multiple ascending doses of LY3540378 administered SC in Japanese Participants.	Drug: LY3540378; Administered IV or SC.; Drug: LY3540378; Administered SC.
Experimental: LY3540378 (Part D); Multiple ascending doses of LY3540378 administered SC in Chinese Participants.	Drug: LY3540378; Administered IV or SC.; Drug: LY3540378; Administered SC.
Placebo Comparator: Placebo (Part A, B, C & D); Placebo administered either IV or SC.	Drug: Placebo; Administered IV or SC.

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 up to Day 113

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3540378	PK: Cmax of LY3540378	Predose on Day 1 through Day 113
PK: Area Under the Concentration Versus Time Curve (AUC) of LY3540378	PK: AUC of LY3540378	Predose on Day 1 through Day 113

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Actual): May 30, 2022
• Study Completion (Actual): May 30, 2022

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: February 23, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 17, 2022
• Last Verified: June 9, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 17793; J3E-MC-EZDA (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