A Drug Interaction Study of LY3154207 in Healthy Participants

Study Overview
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Brief Summary
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The main purpose of this study is to learn more about the safety and side effects of LY3154207 and fluconazole (anti-fungal medication), when taken together by healthy participants. The study will last from nine to 11 weeks for each participant.

Official Title
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Safety and Tolerability of LY3154207 in Combination With a CYP3A4 Inhibitor and Assessment of Pharmacokinetics of LY3154207 After Administration of Capsule and Tablet Formulations in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: LY3154207 Capsule
* Drug: LY3154207 Tablet
* Drug: Placebo
* Drug: Fluconazole Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body mass index (BMI) of 18 to 35 kilogram per meter square (kg/m²) Have clinical laboratory test results within acceptable range for the population Exclusion Criteria: Have consumed grapefruits or grapefruit-containing products, Seville oranges or Seville orange-containing products, star fruits or star fruit-containing products within 7 days prior to dosing or intend to consume during the study Intend to use over-the-counter or prescription medication (with exception of hormonal contraceptives and acetaminophen), including herbal preparations containing St. John's wort, kava, garlic, ginger, ginkgo biloba, or guarana, within 14 days prior to Check-in and during the study Use of any drugs or substances that are known inducers and/or inhibitors of cytochrome P450 (CYP) 3A within 14 days prior to the administration of study drug and during the study Have evidence of active renal disease (eg, diabetic renal disease, polycystic kidney disease) or an estimated creatinine clearance of < 80 milliliters per minute (mL/minute), calculated using the Chronic Kidney Disease Epidemiology Collaboration equation

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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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: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1 Part A - LY3154207 Capsule<br>LY3154207 capsule (reference) administered orally, once. | Drug: LY3154207 Capsule<br>* Administered orally as capsule<br>|
| Experimental: Cohort 1 Part A - LY3154207 Tablet<br>LY3154207 tablet (test) administered orally, once. | Drug: LY3154207 Tablet<br>* Administered orally as tablet<br>|
| Experimental: Cohort 1 Part B LY3154207 (Dose 1) + Fluconazole<br>LY3154207 (dose 1) administered alone, orally once. Fluconazole administered alone, orally, on consecutive days. LY3154207 co-administered with fluconazole on consecutive days. | Drug: LY3154207 Tablet<br>* Administered orally as tablet<br>Drug: Fluconazole Tablet<br>* Administered orally as tablet<br>|
| Experimental: Cohort 1 Part B - Placebo + Fluconazole<br>Placebo administered alone, orally, once. Fluconazole administered alone, orally, on consecutive days. Placebo co-administered with fluconazole on consecutive days. | Drug: Placebo<br>* Administered orally as tablet<br>* Other names: Placebo Tablet;Drug: Fluconazole Tablet<br>* Administered orally as tablet<br>|
| Experimental: Cohort 2 - LY3154207 (Dose 2) + Fluconazole<br>LY3154207 (dose 2) administered alone, orally once. Fluconazole administered alone, orally, on consecutive days. LY3154207 co-administered with fluconazole on consecutive days. | Drug: LY3154207 Tablet<br>* Administered orally as tablet<br>Drug: Fluconazole Tablet<br>* Administered orally as tablet<br>|
| Experimental: Cohort 2 - Placebo + Fluconazole<br>Placebo administered alone, orally once. Fluconazole administered alone, orally, on consecutive days. Placebo co-administered with fluconazole on consecutive days. | Drug: Placebo<br>* Administered orally as tablet<br>* Other names: Placebo Tablet;Drug: Fluconazole Tablet<br>* Administered orally as tablet<br>|
| Experimental: Cohort 3 - LY3154207 + Fluconazole<br>LY3154207 (dose 2) administered alone, orally, on consecutive days. LY3154207 co-administered with fluconazole on consecutive days. | Drug: LY3154207 Tablet<br>* Administered orally as tablet<br>Drug: Fluconazole Tablet<br>* Administered orally as tablet<br>|
| Experimental: Cohort 3 - Placebo + Fluconazole<br>Placebo administered alone, orally, on consecutive days. Placebo co-administered with fluconazole on consecutive days. | Drug: Placebo<br>* Administered orally as tablet<br>* Other names: Placebo Tablet;Drug: Fluconazole Tablet<br>* Administered orally as tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Baseline up to 11 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Blood Pressure (BP) | BP measured by ambulatory blood pressure monitoring (ABPM) | Baseline, up to 48 hours post dose when LY3154207 is co-administered with fluconazole | 
| Change from Baseline in Pulse Rate (PR) | PR measured by ABPM | Baseline, up to 48 hours post dose when LY3154207 is co-administered with fluconazole | 
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3154207 | PK: Cmax of LY3154207 | Baseline up to 48 hours postdose | 
| PK: Area Under the Concentration Versus Time Curve from Time Zero to Time T, where T is the Last Sample with a Measurable Concentration (AUC[0-tlast]) of LY3154207 | PK: AUC(0-tlast) of LY3154207 | Baseline up to 48 hours postdose | 
| PK: Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC[0-inf]) of LY3154207 | PK: AUC(0-inf) of LY3154207 | Baseline up to 48 hours postdose |