A Study Comparing Different Formulations of LY3410738 in Healthy Adult Participants

A Pilot Study Comparing LY3410738 Capsule and Tablet Formulations and Effect of a Low-fat Meal and a Proton Pump Inhibitor on the Single-dose Pharmacokinetics of LY3410738 Tablets in Healthy Adult Subjects

The main purpose of study is to compare different formulations of LY3410738 under fasting condition by looking at the amount of the study drug, LY3410738, that gets into the blood stream and how long it takes the body to get rid of it when given in healthy adult participants. The study will also access the effect of standard low-fat meal and esomeprazole (Proton Pump Inhibitor) on LY3410738. Safety and tolerability of LY3410738 will also be evaluated. For each participant, the total duration of the study will be 56 days for Groups 1 and 2 and up to 61 days for Groups 3 and 4, including screening.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Esomeprazole; Drug: LY3410738

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Daytona Beach, Florida, United States, 32117
      • Labcorp Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m^2), inclusive.
• Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator.
• Female participants of non-childbearing potential and male participants who follow standard contraceptive methods.
• Must have comply with all study procedures, including the 3-night stay at the Clinical Research Unit (CRU) and follow-up phone call.

Exclusion Criteria:

• History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor.
• Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B virus immunoglobulin M (HBV IgM) core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening.
• Positive polymerase chain reaction (PCR) test for COVID-19 at Screening.
• Known ongoing alcohol and/or drug abuse within 2 years prior to Screening.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
• Have previously received LY3410738 in any other study investigating LY3410738, within 30 days prior to Day 1.
• Have history of a major surgical procedure within 30 days prior to Screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Tablet versus Capsule; Treatment A: LY3410738 capsule on Day 1 as a single oral dose in the morning following a fast of at least 10 hours prior to and 4 hours after dosing. Treatment B: LY3410738 tablet on Day 4 as a single oral dose in the morning 10 hours prior to and 4 hours after dosing.	Drug: LY3410738; Administered orally.
Experimental: Group 2: Food Effect Comparison Group; Treatment B: LY3410738 table on Day 1 as a single oral dose in the morning following a fast of at least 10 hours prior to and 4 hours after dosing. Treatment C: LY3410738 table on Day 4 as a single oral dose in the morning 30 minutes after starting a standard low-fat meal.	Drug: LY3410738; Administered orally.
Experimental: Group 3: Potential of Hydrogen (pH) Effect Fasted Group; Treatment B: LY3410738 table on Day 1 as a single oral dose in the morning following a fast of at least 10 hours prior to and 4 hours after dosing. Treatment D: Esomeprazole single oral dose once daily (QD) in the morning on Days 4 through 8 in fasted state followed by a standard low-fat meal. On Day 9, Esomeprazole a single oral dose followed by LY3410738 tablet as a single oral dose in the morning, following a fast of at least 10 hours prior to and 4 hours after esomeprazole and LY3410738 coadministration.	Drug: Esomeprazole; Administered orally.; Drug: LY3410738; Administered orally.
Experimental: Group 4: pH Effect Fed Group; Treatment C: LY3410738 table on Day 1 as a single oral dose in the morning 30 minutes after starting a standard low-fat meal. Treatment E: Esomeprazole as a single oral dose QD in the morning on Days 4 through 8, in fasted state followed by a standard low-fat meal. On Day 9, Esomeprazole as a single oral dose followed by a LY3410738 tablet in the morning in fed state standard low-fat meal.	Drug: Esomeprazole; Administered orally.; Drug: LY3410738; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration-Time Curve from Hour 0 to the Last Measurable Concentration (AUC0-tlast) of LY3410738 Tablets Versus Capsules	PK: AUC0-tlast of LY3410738 Tablets Versus Capsules	Predose up to 48 hours postdose
PK: Area Under the Concentration from Hour 0 Extrapolated to Infinity (AUC0-∞) of LY3410738 Tablets Versus Capsules	PK: AUC0-∞ of LY3410738 Tablets Versus Capsules	Predose up to 48 hours postdose
PK: Maximum Observed Plasma Concentration (Cmax) of LY3410738 Tablets Versus Capsules	PK: Cmax of LY3410738 Tablets Versus Capsules	Predose up to 48 hours postdose
PK: AUC0-tlast of LY3410738 After Standard Low-Fat Meal	PK: AUC0-tlast of LY3410738 After Standard Low-Fat Meal	Predose up to 48 hours postdose
PK: AUC0-∞ of LY3410738 After Standard Low-Fat Meal	PK: AUC0-∞ of LY3410738 After Standard Low-Fat Meal	Predose up to 48 hours postdose
PK: Cmax of LY3410738 After Standard Low-Fat Meal	PK: Cmax of LY3410738 After Standard Low-Fat Meal	Predose up to 48 hours postdose
PK: AUC0-tlast of LY3410738 after Esomeprazole oral dose in the Fasted State	PK: AUC0-tlast of LY3410738 after Esomeprazole oral dose in the Fasted State	Predose up to 48 hours postdose
PK: AUC0-∞ of LY3410738 after Esomeprazole oral dose in the Fasted State	PK: AUC0-∞ of LY3410738 after Esomeprazole oral dose in the Fasted State	Predose up to 48 hours postdose
PK: Cmax of LY3410738 after Esomeprazole oral dose in the Fasted State	PK: Cmax of LY3410738 after Esomeprazole oral dose in the Fasted State	Predose up to 48 hours postdose
PK: AUC0-tlast of LY3410738 after Esomeprazole oral dose in the Fed State	PK: AUC0-tlast of LY3410738 after Esomeprazole oral dose in the Fed State	Predose up to 48 hours postdose
PK: AUC0-∞ of LY3410738 after Esomeprazole oral dose in the Fed State	PK: AUC0-∞ of LY3410738 after Esomeprazole oral dose in the Fed State	Predose up to 48 hours postdose
PK: Cmax of LY3410738 after Esomeprazole oral dose in the Fed State	PK: Cmax of LY3410738 after Esomeprazole oral dose in the Fed State	Predose up to 48 hours postdose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Loxo Oncology, Inc.
• Investigators: Study Director: Yingying Guo-Avrutin, Loxo Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2021
• Primary Completion (Actual): April 28, 2022
• Study Completion (Actual): April 28, 2022

Study Registration Dates

• First Submitted: December 13, 2023
• First Submitted That Met QC Criteria: December 13, 2023
• First Posted (Actual): December 26, 2023

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Formulation, food effect, proton pump inhibitor
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Esomeprazole
• Other Study ID Numbers: LOXO-IDH-21004; I9Y-OX-JDHE (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