A Study of LY4268989 (MORF-057) in Healthy Participants

A Phase 1 Study to Further Investigate the Pharmacokinetics, Safety and Tolerability, Food Effect and Drug-Drug Interaction of LY4268989 (MORF-057) in Healthy Participants

The purpose of this study is to measure the body's absorption and processing of the study drug, the study drug's effect on the body, safety, and tolerability with LY4268989 (MORF-57) in healthy participants, including Japanese and Chinese participants

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: LY4268989; Drug: Placebo; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Actual): 144
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • CenExel ACT

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Are healthy as determined by medical evaluation including medical history, physical examination, laboratory test, electrocardiograms (ECGs), and vital signs.
• Cohort 5 includes Japanese participants. To qualify, the participants must be first-generation Japanese in the US, defined as the participant's biological parents, and all the participant's biological grandparents, being of exclusive Japanese descent, and being born in Japan.
• Cohort 5 includes Chinese participants. To qualify as Chinese for this study, all 4 of the participant's biological grandparents must be of exclusive Chinese descent and born in China.
• Have a body mass index within the range of 18.0 to 32.0 kilogram/square meter (kg/m²), inclusive, at screening.

Exclusion Criteria:

• Have a current or recent acute, active infection. For at least 30 days before screening and up to Day 1, participants must have no symptoms or signs of confirmed or suspected infection, and must have completed any appropriate anti-infective treatment.
• Have presence of significant uncontrolled respiratory, cerebrocardiovascular, cardiovascular, hepatic, renal, gastrointestinal, endocrine, hematologic, neurologic or psychiatric disorders, or abnormal laboratory values at screening that, in the opinion of the sponsor or investigator, pose an unacceptable risk to the participant if participating in the study or of interfering with the interpretation of data.
• Are immunocompromised to an extent that participation in the study would pose an unacceptable risk to the participant as determined by the investigator.
• Use or intend to use prescription or nonprescription medication, including dietary supplements, vitamins, herbal supplements, traditional Chinese medicine, or alternative medicines, within 14 days or 5 half-lives (whichever is longer), prior to dosing, unless, in the opinion of the investigator and sponsor, the medication will not interfere with the study

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: LY4268989 or Placebo Cohort 1 (Blinded); Participants will receive LY4268989 orally or placebo single dose followed by BID administration	Drug: LY4268989; Administered orally; Drug: Placebo; Administered placebo
Experimental: LY4268989 Cohort 2 (Open-Label); Participants will receive LY4268989 orally tablet (formulation compared to capsule formulation) in a fasted state	Drug: LY4268989; Administered orally
Experimental: LY4268989 Cohort 3 (Open-Label); Participants will receive multiple doses of LY4268989 orally BID administration with midazolam orally and intravenously (IV).	Drug: Midazolam; Administered orally; Drug: LY4268989; Administered orally; Drug: Midazolam; Administered intravenously (IV)
Experimental: LY4268989 or Placebo Cohort 4 (Blinded); Participants will receive single escalating doses of LY4268989 orally or placebo	Drug: LY4268989; Administered orally; Drug: Placebo; Administered placebo
Experimental: LY4268989 Cohort 5 (Blinded); Participants will receive multiple doses of LY4268989 orally or placebo	Drug: LY4268989; Administered orally; Drug: Placebo; Administered placebo
Experimental: LY4268989 Cohort 6 (Open-Label); Participants will receive LY4268989 single dose orally in a fasted and fed state	Drug: LY4268989; Administered orally
Experimental: LY4268989 Cohort 7 (Open-Label); Participants will receive multiple doses of LY4268989 orally BID administration in a fed state	Drug: LY4268989; Administered orally
Experimental: LY4268989 Cohort 8 (Open-Label); Participants will receive multiple doses of LY4268989 orally BID administration with midazolam IV in a fasted state.	Drug: Midazolam; Administered orally; Drug: LY4268989; Administered orally; Drug: Midazolam; Administered intravenously (IV)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY4268989 (Cohort 1) and (Cohort 5)		Day 1 to Day 17
PK: Area Under the Concentration Curve (AUC) of LY4268989 (Cohort 1) and (Cohort 5)		Day 1 to Day 17
Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) (Cohort 1), (Cohort 3), and (Cohort 5)	A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module	Baseline to Study Completion (Up to Day 17)
Number of Participants with TEAEs and SAEs (Cohort 4)	A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the reported adverse events module	Baseline to Study Completion (Up to Period 4, Day 4)
PK: Cmax of LY4268989 (Cohort 2)		Day 1 to Day 13
PK: AUC of LY4268989 (Cohort 2)		Day 1 to Day 13
PK: Cmax of Midazolam and 1'-Hydroxymidazolam (Cohort 3)	PK of midazolam and 1'-hydroxymidazolam (Cmax), when midazolam is administered alone and in the presence of LY4268989	Day 1 to Day 17
PK: Cmax of LY4268989 (Cohort 6)		Day 1 to Day 7
PK: AUC of LY4268989 (Cohort 6)		Day 1 to Day 7
PK: Cmax of LY4268989 (Cohort 7)		Day 1 to Day 12
PK: AUC of LY4268989 (Cohort 7)		Day 1 to Day 12
PK: AUC of Midazolam and 1'-Hydroxymidazolam (Cohort 3)	PK of midazolam and 1'-hydroxymidazolam (AUC), where midazolam is administered alone and in the presence of LY4268989	Day 1 to Day 17
PK: AUC of Midazolam and 1'-Hydroxymidazolam (Cohort 8)	PK of midazolam and 1'-hydroxymidazolam (AUC), where midazolam is administered alone and in the presence of LY4268989	Day 3 and Day 11
PK: Cmax of Midazolam and 1'-Hydroxymidazolam (Cohort 8)	PK of midazolam and 1'-hydroxymidazolam (Cmax), when midazolam is administered alone and in the presence of LY4268989	Day 3 to Day 11

Secondary Outcome Measures

Outcome Measure	Time Frame
PK: Cmax of LY4268989 (Cohort 4)	Day 1 to Day 4
PK: AUC of LY4268989 (Cohort 4)	Day 1 to Day 4
PK: Cmax of LY4268989 (Cohort 3)	Time Frame: Day 6 to Day 15
PK: AUC of LY4268989 (Cohort 3)	Time Frame: Day 6 to Day 15
PK: Cmax of LY4268989 (Cohort 8)	Time Frame: Day 3 and Day 10
PK: AUC of LY4268989 (Cohort 8)	Time Frame: Day 3 and Day 10

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 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2025
• Primary Completion (Actual): February 17, 2026
• Study Completion (Actual): February 17, 2026

Study Registration Dates

• First Submitted: May 1, 2025
• First Submitted That Met QC Criteria: May 1, 2025
• First Posted (Actual): May 9, 2025

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Midazolam
• Other Study ID Numbers: 27387; J6E-MC-KWAC (Other Identifier: Eli Lilly and Company); MORF-057 (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