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

NCT06503679 | Completed Phase 1 FDA Drug

• 2 other identifiers: 27110J5C-MC-FOAF, DC-853104
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

LY4100511; DC-853

Outcome Measures

Primary Outcomes (12)

• 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

Study Arms (3)

LY4100511 Dose 1 + Midazolam + Repaglinide (Cohort 1)

EXPERIMENTAL

Participants will receive an oral dose 1 of LY4100511 and single dose of midazolam and repaglinide.

Drug: LY4100511 (DC-853) Dose 1; Drug: Midazolam; Drug: Repaglinide

LY4100511 Dose 2 + Midazolam + Repaglinide (Cohort 2)

EXPERIMENTAL

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: LY4100511 (DC-853) Dose 2; Drug: Midazolam; Drug: Repaglinide

LY4100511 Dose 3 + Digoxin and Rosuvastatin (Cohort 3)

EXPERIMENTAL

Participants will recive an oral dose 3 of LY4100511 and single dose of digoxin and rosuvastatin.

Drug: LY4100511 (DC-853) Dose 3; Drug: Digoxin; Drug: Rosuvastatin

Interventions

LY4100511 (DC-853) Dose 1 DRUG

Administered orally

LY4100511 Dose 1 + Midazolam + Repaglinide (Cohort 1)

LY4100511 (DC-853) Dose 2 DRUG

Administered orally

LY4100511 Dose 2 + Midazolam + Repaglinide (Cohort 2)

LY4100511 (DC-853) Dose 3 DRUG

Administered orally

LY4100511 Dose 3 + Digoxin and Rosuvastatin (Cohort 3)

Midazolam DRUG

Administered orally

LY4100511 Dose 1 + Midazolam + Repaglinide (Cohort 1); LY4100511 Dose 2 + Midazolam + Repaglinide (Cohort 2)

Repaglinide DRUG

Administered orally

LY4100511 Dose 1 + Midazolam + Repaglinide (Cohort 1); LY4100511 Dose 2 + Midazolam + Repaglinide (Cohort 2)

Digoxin DRUG

Administered orally

LY4100511 Dose 3 + Digoxin and Rosuvastatin (Cohort 3)

Rosuvastatin DRUG

Administered orally

LY4100511 Dose 3 + Digoxin and Rosuvastatin (Cohort 3)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• DICE Therapeutics, Inc., a wholly owned subsidiary of Eli Lilly and Company: lead

Study Sites (1)

Fortrea Clinical Research Unit

Dallas, Texas, 75247, United States

Location

MeSH Terms

Interventions

Midazolam; repaglinide; Digoxin; Rosuvastatin Calcium

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring

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: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 16, 2024
• Study Start: July 16, 2024
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: January 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)