A Drug Interaction Study of LY3871801 in Healthy Participants

Evaluation of the Effect of LY3871801 on the Pharmacokinetics of CYP450 Substrates and an OAT1/3 Substrate in Healthy Participants

The main purpose of this study is to determine the effect of LY3871801 when administered orally on the levels of methotrexate (part 1), drug cocktail (warfarin, dextromethorphan, and midazolam) and repaglinide (part 2) in the blood stream when administered orally in healthy participants. The information about any adverse effects experienced will be collected and the tolerability of LY3871801 will also be evaluated. The study may last up to approximately 25 days for each participant.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: LY3871801; Drug: Warfarin; Drug: Methotrexate; Drug: Dextromethorphan; Drug: Repaglinide

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical evaluation including medical history and physical examination.
• Have body weight ≥ 45 kilograms (kg) and body mass index (BMI) within the range 18.5 to 40.0 kilograms per meter squared (kg/m²)
• Male or female participants not of childbearing potential (both parts) and for part 2, female participants of child bearing potential are eligible.

Exclusion Criteria:

• Have known allergies to LY3871801, related compounds, or any components of the formulation, or history of significant atopy.
• Have known allergies to drugs including methotrexate, folic acid, repaglinide, warfarin, dextromethorphan, and midazolam that would pose an unacceptable risk to the participant.
• Have an abnormal blood pressure and/or pulse rate, deemed to be clinically significant by the investigator
• Have used or intend to use prescription or nonprescription medication
• Have a positive (not indeterminate) QuantiFERON®-TB Gold test

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3871801 + Methotrexate (Part 1); LY3871801 administered orally in combination with methotrexate given orally.	Drug: LY3871801; Administered orally.; Drug: Methotrexate; Administered orally.
Experimental: LY3871801 + Repaglinide + Drug Cocktail (Part 2); LY3871801 administered orally in combination with repaglinide given orally and drug cocktail which includes warfarin, dextromethorphan and midazolam administered orally.	Drug: Midazolam; Administered orally.; Drug: LY3871801; Administered orally.; Drug: Warfarin; Administered orally.; Drug: Dextromethorphan; Administered orally.; Drug: Repaglinide; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Methotrexate	Part 1: PK: Cmax of Methotrexate	Predose up to 48 hours postdose
Part 1: PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Methotrexate	Part 1: PK: AUC[0-∞] of Methotrexate	Predose up to 48 hours postdose
Part 2: PK: Cmax of Midazolam	Part 2: PK: Cmax of Midazolam	Predose up to 24 hours postdose
Part 2: PK: AUC[0-∞] of Midazolam	Part 2: PK: AUC[0-∞] of Midazolam	Predose up to 24 hours postdose
Part 2: PK: Cmax of S-warfarin	Part 2: PK: Cmax of S-warfarin	Predose up to 96 hours postdose
Part 2: PK: AUC[0-∞] of S-warfarin	Part 2: PK: AUC[0-∞] of S-warfarin	Predose up to 96 hours postdose
Part 2: PK: Cmax of Dextromethorphan	Part 2: PK: Cmax of Dextromethorphan	Predose up to 72 hours postdose
Part 2: PK: AUC[0-∞] of Dextromethorphan	Part 2: PK: AUC[0-∞] of Dextromethorphan	Predose up to 72 hours postdose
Part 2: PK: Cmax of Repaglinide	Part 2: PK: Cmax of Repaglinide	Predose up to 24 hours postdose
Part 2: PK: AUC[0-∞] of Repaglinide	Part 2: PK: AUC[0-∞] of Repaglinide	Predose up to 24 hours postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2022
• Primary Completion (Actual): March 29, 2023
• Study Completion (Actual): March 29, 2023

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: October 28, 2022
• First Posted (Actual): November 2, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Respiratory System Agents; Anticoagulants; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Antitussive Agents; Midazolam; Methotrexate; Dextromethorphan; Warfarin; Repaglinide
• Other Study ID Numbers: 18336; J3P-MC-FTAD (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