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

NCT06964776 | Completed Phase 1 FDA Drug

• 3 other identifiers: 27387J6E-MC-KWACMORF-057
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy

Outcome Measures

Primary Outcomes (14)

• 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: 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 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 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

• 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

Secondary Outcomes (6)

• 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

Study Arms (8)

LY4268989 or Placebo Cohort 1 (Blinded)

EXPERIMENTAL

Participants will receive LY4268989 orally or placebo single dose followed by BID administration

Drug: LY4268989; Drug: Placebo

LY4268989 Cohort 2 (Open-Label)

EXPERIMENTAL

Participants will receive LY4268989 orally tablet (formulation compared to capsule formulation) in a fasted state

Drug: LY4268989

LY4268989 Cohort 3 (Open-Label)

EXPERIMENTAL

Participants will receive multiple doses of LY4268989 orally BID administration with midazolam orally and intravenously (IV).

Drug: LY4268989; Drug: Midazolam

LY4268989 or Placebo Cohort 4 (Blinded)

EXPERIMENTAL

Participants will receive single escalating doses of LY4268989 orally or placebo

Drug: LY4268989; Drug: Placebo

LY4268989 Cohort 5 (Blinded)

EXPERIMENTAL

Participants will receive multiple doses of LY4268989 orally or placebo

Drug: LY4268989; Drug: Placebo

LY4268989 Cohort 6 (Open-Label)

EXPERIMENTAL

Participants will receive LY4268989 single dose orally in a fasted and fed state

Drug: LY4268989

LY4268989 Cohort 7 (Open-Label)

EXPERIMENTAL

Participants will receive multiple doses of LY4268989 orally BID administration in a fed state

Drug: LY4268989

LY4268989 Cohort 8 (Open-Label)

EXPERIMENTAL

Participants will receive multiple doses of LY4268989 orally BID administration with midazolam IV in a fasted state.

Drug: LY4268989; Drug: Midazolam

Interventions

Midazolam DRUG

Administered orally

LY4268989 Cohort 3 (Open-Label)

LY4268989 DRUG

Administered orally

LY4268989 Cohort 2 (Open-Label); LY4268989 Cohort 3 (Open-Label); LY4268989 Cohort 5 (Blinded); LY4268989 Cohort 6 (Open-Label); LY4268989 Cohort 7 (Open-Label); LY4268989 Cohort 8 (Open-Label); LY4268989 or Placebo Cohort 1 (Blinded); LY4268989 or Placebo Cohort 4 (Blinded)

Placebo DRUG

Administered placebo

LY4268989 Cohort 5 (Blinded); LY4268989 or Placebo Cohort 1 (Blinded); LY4268989 or Placebo Cohort 4 (Blinded)

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

CenExel ACT

Anaheim, California, 92801, United States

Location

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• 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 DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Cohort 1, 4 and 5 are blinded while Cohort 2, 3, 6, 7, and 8 are open label.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2025
• First Posted: May 9, 2025
• Study Start: May 1, 2025
• Primary Completion: February 17, 2026
• Study Completion: February 17, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)