A Drug-drug Interaction Study Evaluating the Perpetrator Potential of LY4100511 (DC-853) on Midazolam, Repaglinide, Digoxin, Rosuvastatin in Healthy Participants

A Phase 1, Single-center, Open-label, Fixed-sequence, Crossover Study to Evaluate the Effect of LY4100511 (DC-853) on the Single-dose Pharmacokinetics of Midazolam, Repaglinide, Digoxin, and Rosuvastatin in Healthy Participants

The main purpose of this study is to assess the safety and tolerability and pharmacokinetics of LY4100511 (DC-853) when administered alone or in the presence of cytochrome P450 substrates in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Digoxin; Drug: Midazolam; Drug: LY4100511 (DC-853) Dose 1; Drug: Repaglinide; Drug: LY4100511 (DC-853) Dose 2; Drug: LY4100511 (DC-853) Dose 3

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Fortrea Clinical Research Unit

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Females must be of childbearing potential
• Males must agree to use contraception
• Have body mass index (BMI) between 18.0 and 32.0 kilogram/square meter (kg/m²), inclusive, and a body weight of greater than or equal to 50 kg.
• In good health, as determined by no clinically significant findings from medical history, 12-lead ECG and vital signs measurements, and clincial laboratory evaluations (congentical nonhemolytic hyperbilirubinemia) at screening and check-in, and from the physical examination at check-in as assessed by the investigator.

Exclusion Criteria:

• Have a 12-lead ECG abnormality that, in the opinion of the investigator,

  • increases the risks associated with participating in the study
  • may confound ECG data analysis

  • a QTCF >450 msec for males, or >470 msec for females

    • short PR interval <120 msec or PR interval >220 msec
    • second or third degree atrioventricular block
    • intraventricular conduction delay with QRS >120 msec
    • complete right bundle branch block
    • left bundle branch block, or
    • Wolff Parkinson-White syndrome.
• Have had current or recent acute infection
• Show evidence of active or latent tuberculosis (TB)
• Had any surgical procedures within 12 weeks prior to screening or any planned surgical procedure scheduled to occur during the study.
• Have a history or presence of multiple or severe allergies, or an anaphylactic reaction to prescription or non prescription drugs.
• Are immunocompromised
• Presence of active suicidal ideation or positive suicide behavior using baseline/screening version of the C-SSRS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY4100511 Dose 1 + Midazolam + Repaglinide (Cohort 1); Participants will receive an oral dose 1 of LY4100511 and single dose of midazolam and repaglinide.	Drug: Midazolam; Administered orally; Drug: LY4100511 (DC-853) Dose 1; Administered orally; Drug: Repaglinide; Administered orally
Experimental: LY4100511 Dose 2 + Midazolam + Repaglinide (Cohort 2); Participants will receive up to an oral dose 2 of LY4100511 and single dose of midazolam and repaglinide. Dosing will not proceed until a satisfactory review of the safety and tolerability data from lower dose level is performed.	Drug: Midazolam; Administered orally; Drug: Repaglinide; Administered orally; Drug: LY4100511 (DC-853) Dose 2; Administered orally
Experimental: LY4100511 Dose 3 + Digoxin and Rosuvastatin (Cohort 3); Participants will recive an oral dose 3 of LY4100511 and single dose of digoxin and rosuvastatin.	Drug: Rosuvastatin; Administered orally; Drug: Digoxin; Administered orally; Drug: LY4100511 (DC-853) Dose 3; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics (PK): Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC [0-∞]) of Midazolam, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
Pharmacokinetics (PK): Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC [0-∞]) of 1-Hydroxymidazolam, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
Pharmacokinetics (PK): Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC [0-∞]) of Repaglinide, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
Pharmacokinetics (PK): Area Under the Concentration-Time Curve from Time Zero to Infinity (AUC [0-∞]) of Digoxin, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
PK: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC[0-tlast]) of Midazolam, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
PK: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC[0-tlast]) of 1-Hydroxymidazolam, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
PK: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC[0-tlast]) of Repaglinide,in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
PK: Area Under the Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC[0-tlast]) of Digoxin, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
PK: Maximum Observed Concentration (Cmax) of Midazolam, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
PK: Maximum Observed Concentration (Cmax) of 1-Hydroxymidazolam, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
PK: Maximum Observed Concentration (Cmax) of Repaglinide, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
PK: Maximum Observed Concentration (Cmax) of Digoxin, in the absence or presence of steady-state LY4100511	Day 1 and Day 9: Predose, Up to 48 Hours Post Dose

Collaborators and Investigators

• Sponsor: DICE Therapeutics, Inc., a wholly owned subsidiary of 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): July 16, 2024
• Primary Completion (Actual): December 31, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: July 10, 2024
• First Submitted That Met QC Criteria: July 10, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 23, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: DC-853; LY4100511
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hypoglycemic Agents; Enzyme Inhibitors; Antimetabolites; Anesthetics; Central Nervous System Depressants; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Midazolam; Digoxin; Repaglinide
• Other Study ID Numbers: 27110; J5C-MC-FOAF, DC-853104 (Other Identifier: DICE Therapeutics, a wholly owned subsidiary of 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