A Study of LY3540378 in Healthy Participants

NCT04768855 | Completed Phase 1 FDA Drug

• 2 other identifiers: 17793J3E-MC-EZDA
• Study Type: interventional
• Target: 134
• Locations: 2 countries
• Sites: 2

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3540378

  Predose on Day 1 through Day 113

• PK: Area Under the Concentration Versus Time Curve (AUC) of LY3540378

  Predose on Day 1 through Day 113

Study Arms (5)

LY3540378 (Part A)

EXPERIMENTAL

Single ascending doses of LY3540378 administered either intravenously (IV) or subcutaneously (SC).

Drug: LY3540378

LY3540378 (Part B)

EXPERIMENTAL

Multiple ascending doses of LY3540378 administered SC.

Drug: LY3540378

LY3540378 (Part C)

EXPERIMENTAL

Multiple ascending doses of LY3540378 administered SC in Japanese Participants.

Drug: LY3540378

LY3540378 (Part D)

EXPERIMENTAL

Multiple ascending doses of LY3540378 administered SC in Chinese Participants.

Drug: LY3540378

Placebo (Part A, B, C & D)

PLACEBO COMPARATOR

Placebo administered either IV or SC.

Drug: Placebo

Interventions

LY3540378 DRUG

Administered IV or SC.

LY3540378 (Part A)

Placebo DRUG

Administered IV or SC.

Placebo (Part A, B, C & D)

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (2)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Lilly Centre for Clinical Pharmacology

Singapore, 138623, Singapore

Location

Related Publications (1)

• Tham LS, Heerspink HJL, Wang X, Verdino P, Saifan CG, Benson EA, Goldsmith P, Wang Z, Testani JM, Haupt A, Sam F, Cherney DZI. Volenrelaxin (LY3540378) increases renal plasma flow: a randomized Phase 1 trial. Nephrol Dial Transplant. 2024 Dec 20;40(1):109-122. doi: 10.1093/ndt/gfae112.

  PMID: 38782726 DERIVED

Study Officials

• 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 DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2021
• First Posted: February 24, 2021
• Study Start: March 17, 2021
• Primary Completion: May 30, 2022
• Study Completion: May 30, 2022
• Last Updated: June 21, 2022

Record last verified: 2022-06-09

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1); US (1)