A Drug Interaction Study of LY3154207 in Healthy Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: LY3154207 Capsule; Drug: LY3154207 Tablet; Drug: Fluconazole Tablet; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Covance Clinical Research Inc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

8

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 21, 2019
• Primary Completion (ACTUAL): December 28, 2019
• Study Completion (ACTUAL): December 28, 2019

Study Registration Dates

• First Submitted: May 7, 2019
• First Submitted That Met QC Criteria: May 7, 2019
• First Posted (ACTUAL): May 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 16, 2020
• Last Verified: January 15, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: 16304; I7S-MC-HBEF (OTHER: 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