Clinical trial NCT06503679: A Drug-drug Interaction Study Evaluating the Perpetrator Potential of LY4100511 (DC-853) on Midazolam, Repaglinide, Digoxin, Rosuvastatin in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: LY4100511
DC-853
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2024-07-16
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: 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
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: 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
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: 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
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: 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
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: 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
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: 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
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: 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
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: PK: Maximum Observed Concentration (Cmax) of Midazolam, in the absence or presence of steady-state LY4100511
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: PK: Maximum Observed Concentration (Cmax) of 1-Hydroxymidazolam, in the absence or presence of steady-state LY4100511
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: PK: Maximum Observed Concentration (Cmax) of Repaglinide, in the absence or presence of steady-state LY4100511
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
measure: PK: Maximum Observed Concentration (Cmax) of Digoxin, in the absence or presence of steady-state LY4100511
timeFrame: Day 1 and Day 9: Predose, Up to 48 Hours Post Dose
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Fortrea Clinical Research Unit
state: Texas
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References: