A Drug-Drug Interaction (DDI) Study of LY3437943 in Obese 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 LY3437943 when administered subcutaneously on the levels of midazolam, warfarin and caffeine in the blood stream when administered orally as a drug cocktail in obese participants. This study will last up to approximately 25 weeks for each participant.

Official Title
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A Multiple-Dose Drug-Drug Interaction Study to Determine the Effect of LY3437943 on Drug Metabolizing Enzymes

Conditions
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Obesity

Intervention / Treatment
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* Drug: LY3437943
* Drug: Midazolam
* Drug: Warfarin
* Drug: Caffeine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index (BMI) within the range 27.0 to 40.0 kilograms per meter squared (kg/m²) Male and female participants of childbearing potential who agree to use contraceptive methods Exclusion Criteria: Have a history of diabetes or current diagnosis of diabetes History or presence of a of significant bleeding disorder Participants with significant comorbidity Participants receiving treatment with midazolam, warfarin, inhibitors or inducers of cytochrome P450 (CYP) -1A2, CYP2C9, or CYP3A4 enzymes, or drugs are CYP substrates and have a narrow therapeutic index

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: LY3437943 + Drug Cocktail<br>Midazolam in combination with warfarin and caffeine (drug cocktail) administered orally followed by LY3437943 administered subcutaneously (SC) in week 1. At weeks 8, 12, & 16, the LY3437943 will be administered SC on Day 1 followed by midazolam in combination with warfarin and caffeine (drug cocktail) administered orally on Day 2. | Drug: LY3437943<br>* Administered SC.<br>Drug: Midazolam<br>* Administered orally.<br>Drug: Warfarin<br>* Administered orally.<br>Drug: Caffeine<br>* Administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Midazolam | PK: AUC[0-∞] of Midazolam | Predose up to 24 hours postdose | 
| PK: Maximum Observed Concentration (Cmax) of Midazolam | PK: Cmax of Midazolam | Predose up to 24 hours postdose | 
| PK: AUC[0-∞] of Warfarin | PK: AUC[0-∞] of Warfarin | Predose up to 96 hours postdose | 
| PK: Cmax of Warfarin | PK: Cmax of Warfarin | Predose up to 96 hours postdose | 
| PK: AUC[0-∞] of Caffeine | PK: AUC[0-∞] of Caffeine | Predose up to 48 hours postdose | 
| PK: Cmax of Caffeine | PK: Cmax of Caffeine | Predose up to 48 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Overweight, Obesity, Drug Interaction, Cocktail, Pharmacokinetic