A First-In-Human Study of LY3839840 in Healthy Participants

Single- and Multiple-Ascending Dose Study to Evaluate the Safety and Pharmacokinetics of LY3839840 Following Oral Dosing in Healthy Participants

The main purpose of this first-in-human study to investigate the safety of LY3839840 in single and multiple doses, and how it's processed in the body when given in different amounts.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: Midazolam; Drug: LY3839840

Detailed Description

The study will be conducted in five parts (A, B, C, D, and E) and each enrolled participant will receive a single dose (Parts A and C) or multiple dose (Parts B, C and D) of either LY3839840 or placebo. Part E will study midazolam alone and with LY3839840. The study will last up to approximately 7 weeks for parts A, C (single dose cohort), 8 weeks for parts B, D and C (multiple dose cohort), and up to 3 weeks for Part E.

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • CenExel ACT
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Fortrea Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Healthy men and women. Women may only be included if they are of nonchildbearing potential

For Part C:

• Part C of the study includes Chinese participants only. To qualify, the participants must be considered as native Chinese, defined as all the participant's biological grandparents being of Chinese origin

For Part D:

• Part D of the study includes Japanese participants only. To qualify, the participants must be first-generation Japanese, defined as the participant's biological parents, and all the participant's biological grandparents, being of exclusive Japanese descent, and being born in Japan
• Participants who are healthy as determined through medical evaluation including medical history, physical examination, laboratory tests, vital signs, and 12-lead (electrocardiogram ECG)
• Have a body mass index (BMI) of greater than or equal to 18 to less than or equal to 35 kilograms per square meter (kg/m²). For Parts C and D: BMI greater than or equal to 18 to less than or equal to 29 kilograms per square meter (kg/m²)
• Participants who have laboratory tests within the normal reference range for the population or CRU or have results with acceptable deviations that are judged by the investigator not to be clinically significant
• Have venous access sufficient to allow for blood sampling

Exclusion Criteria:

• Have known allergies to LY3839840, related compounds, or any components of the formulation
• Have a history or presence of multiple or severe allergies, anaphylactic reaction to prescription or nonprescription drugs, or history of significant atopy
• Have a significant history of or current rheumatologic, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine (such as Cushing syndrome, hyperthyroidism, hyperaldosteronism), hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the investigational medicinal product; or of interfering with the interpretation of data
• Have had any significant infections within 3 months prior to the screening visit, or develop any of these infections before the randomization visit.
• Have received ≥1 live vaccine within 28 days of screening, or intend to during the study, or ≤28 days after the study
• Had any surgical procedure (except for minor surgery requiring local or no anesthesia and without any complications or sequelae) within 12 weeks prior to screening, or intend to during the study, or ≤28 days after the study
• Had any malignancy within the past 5 years. Exceptions: successfully treated basal cell skin carcinoma or squamous cell skin carcinoma with no evidence of recurrence or metastatic disease within the past 3 years
• Have a history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection that, in the opinion of the sponsor or investigator, poses an unacceptable risk to the participant
• Have used, or intend to use, prescription or nonprescription medication within 14 days prior to dosing (or 5 half-lives - whichever is longer)
• Are currently enrolled in any other clinical study involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study
• Have participated in a clinical study involving an investigational product within the last 30 days of the final drug administration (or 5 half-lives - whichever is longer)
• Show evidence of active or latent TB
• Are females who are lactating or have a positive pregnancy test at screening or Day -1
• Blood donation of ≥450 mL, or participation in a clinical study that required a blood volume of ≥400 mL since the last study visit within the past 120 days

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3839840 (Part A); Single ascending dose of LY3839840 administered orally.	Drug: LY3839840; Administered orally.
Experimental: LY3839840 (Part C); Single and multiple dose of LY3839840 administered orally in Chinese participants.	Drug: LY3839840; Administered orally.
Experimental: LY3839840 (Part D); Multiple ascending dose of LY3839840 administered orally in Japanese participants.	Drug: LY3839840; Administered orally.
Experimental: LY3839840 (Part B) Cohort 1-3; Multiple ascending dose of LY3839840 administered orally.	Drug: LY3839840; Administered orally.
Experimental: LY3839840 (Part B) Cohort 4; Multiple ascending dose of LY3839840 administered orally.	Drug: LY3839840; Administered orally.
Experimental: LY3839840 (Part B) Optional Cohort 5; Multiple ascending dose of LY3839840 administered orally pending data from Cohort 4	Drug: LY3839840; Administered orally.
Placebo Comparator: Placebo (Parts A-D); Placebo administered orally.	Drug: Placebo; Administered orally.
Experimental: Midazolam (Part E); Midazolam substrate alone or with LY3839840 administered orally	Drug: Midazolam; Administered orally; Drug: LY3839840; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with one or more Adverse Event (s) (AEs), 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 AEs, TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module	Baseline up to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3839840	PK:Cmax of LY3839840	Predose on day 1 up to 14 days post dose
PK: Area Under the Concentration Versus Time Curve (AUC) of LY3839840	PK: AUC of LY3839840	Predose on day 1 up to 14 days post dose
PK: AUC of Midazolam	PK: AUC of Midazolam	Predose on day 1 up to 19 days post-dose
PK: Cmax of Midazolam	PK: Cmax of Midazolam	Predose on day 1 up to 19 days post-dose

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): December 4, 2023
• Primary Completion (Actual): May 22, 2025
• Study Completion (Actual): May 22, 2025

Study Registration Dates

• First Submitted: November 22, 2023
• First Submitted That Met QC Criteria: November 23, 2023
• First Posted (Actual): December 1, 2023

Study Record Updates

• Last Update Posted (Actual): June 6, 2025
• Last Update Submitted That Met QC Criteria: June 3, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anesthetics; Central Nervous System Depressants; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: 18798 (HSREB); J4U-MC-KTAA (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