A Study of LY3540378 in Healthy Participants

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: LY3540378; Drug: Placebo

• Registration Number: NCT04768855
• 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 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-23
• Study First Submitted QC: 2021-02-23
• Study First Posted: 2021-02-24
• Study Start: 2021-03-17
• Primary Completion: 2022-05-30
• Study Completion: 2022-05-30
• Status Verified: 2022-06-09
• Last Update Submitted: 2022-06-17
• Last Update Posted: 2022-06-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 134

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
LY3540378 (Part A)	LY3540378	Single ascending doses of LY3540378 administered either intravenously (IV) or subcutaneously (SC).
LY3540378 (Part B)	LY3540378	Multiple ascending doses of LY3540378 administered SC.
LY3540378 (Part C)	LY3540378	Multiple ascending doses of LY3540378 administered SC in Japanese Participants.
LY3540378 (Part D)	LY3540378	Multiple ascending doses of LY3540378 administered SC in Chinese Participants.
Placebo (Part A, B, C & D)	Placebo	Placebo administered either IV or SC.

Primary Outcome Measures

Name	Time	Method
Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Baseline up to Day 113	A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3540378	Predose on Day 1 through Day 113	PK: Cmax of LY3540378
PK: Area Under the Concentration Versus Time Curve (AUC) of LY3540378	Predose on Day 1 through Day 113	PK: AUC of LY3540378

Trial Locations

Locations (2)

Anaheim Clinical Trials, LLC; 🇺🇸 Anaheim, California, United States

Lilly Centre for Clinical Pharmacology; 🇸🇬 Singapore, Singapore