A Drug Interaction Study of LY3871801 in Healthy Participants

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy

Intervention / Treatment
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* Drug: LY3871801
* Drug: Methotrexate
* Drug: Warfarin
* Drug: Dextromethorphan
* Drug: Midazolam
* Drug: Repaglinide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |