A Study of Imlunestrant (LY3484356) in Female Healthy Participants

The Effect of Imlunestrant on CYP2C8, CYP2C19, CYP2D6, P-gp, and BCRP Activity and the Effect of P-gp Inhibition on Imlunestrant Pharmacokinetics in Healthy Women of Non-childbearing Potential

The main purpose of this study is to evaluate the effect of imlunestrant on repaglinide, omeprazole and dextromethorphan, and rosuvastatin and digoxin. The study will also investigate the effect of quinidine on imlunestrant in female healthy participants of non-childbearing potential. The safety and tolerability of imlunestrant will be investigated in female healthy participants of non-childbearing potential. The study will last approximately up to 32 days for each participant excluding the screening period.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Imlunestrant; Drug: Dextromethorphan; Drug: Repaglinide; Drug: Rosuvastatin; Drug: Omeprazole; Drug: Quinidine; Drug: Digoxin

• Study Type: Interventional
• Enrollment (Actual): 113
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Cypress, California, United States, 90630
      • Altasciences Clinical Los Angeles, Inc
  • Florida
    • South Miami, Florida, United States, 33143-4875
      • Qps-Mra, Llc
  • Texas
    • San Antonio, Texas, United States, 78209
      • ICON Early Phase Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical assessment
• Body mass index (BMI) within the range 18.0 to 35.0 kilograms per meter squared (kg/m²)
• Female participants of non childbearing potential.

Exclusion Criteria:

• Have known allergies to imlunestrant, related compounds or any components of the formulation, repaglinide, omeprazole, dextromethorphan, quinidine, rosuvastatin, or digoxin, as appropriate, or history of significant atopy.
• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator
• Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's wort, within 30 days prior to dosing
• Use or intend to use any prescription medications/products within 14 days prior to first dose until completion of the follow-up visit, unless deemed acceptable by the investigator (or designee), including but not limited to medications that inhibit or induce cytochrome P450 (CYP) 2C8, CYP2C19, CYP2D6, P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP).

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: Imlunestrant + Repaglinide (Cohort 1); Participants received: Day 1: A single oral dose of 0.5 mg repaglinide administered alone. Day 3: A single oral dose of 800 mg imlunestrant, followed approximately 2 hours later by 0.5 mg repaglinide, both administered orally.	Drug: Imlunestrant; Administered orally.; Other Names: LY3484356; Drug: Repaglinide; Administered orally.
Experimental: mlunestrant + Omeprazole & Dextromethorphan (Cohort 2); Participants received: Day 1: A single oral dose of 20 mg omeprazole and 30 mg dextromethorphan, administered in the morning. Day 3: A single oral dose of 800 mg imlunestrant, followed immediately by 20 mg omeprazole and 30 mg dextromethorphan, all administered orally.	Drug: Imlunestrant; Administered orally.; Other Names: LY3484356; Drug: Dextromethorphan; Administered orally.; Drug: Omeprazole; Administered orally.
Experimental: Imlunestrant + Quinidine (Cohort 3); Participants received: Day 1: A single oral dose of 400 mg imlunestrant, administered in the morning. Days 15 to 17 and 19 to 24: Twice-daily oral doses of 200 mg quinidine, administered alone. Day 18: A single oral dose of 400 mg imlunestrant administered in combination with 200 mg quinidine (quinidine was dosed twice on this day as part of the regular regimen).	Drug: Imlunestrant; Administered orally.; Other Names: LY3484356; Drug: Quinidine; Administered orally.
Experimental: Imlunestrant + Rosuvastatin & Digoxin (Cohort 4); Participants received: Day 1: A single oral dose of 10 mg rosuvastatin and 0.25 mg digoxin, administered in the morning. Day 10: A single oral dose of 400 mg imlunestrant, administered in combination with 10 mg rosuvastatin and 0.25 mg digoxin, all administered orally.	Drug: Imlunestrant; Administered orally.; Other Names: LY3484356; Drug: Rosuvastatin; Administered orally.; Drug: Digoxin; Administered orally.

What is the study measuring?

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 Repaglinide (Cohort 1)	PK: AUC[0-∞] of Repaglinide	Day 1 and Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose
PK: Maximum Observed Concentration (Cmax) of Repaglinide (Cohort 1)	PK: Cmax of Repaglinide	Day 1 and Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 hours post-dose
PK: AUC[0-∞] of Omeprazole (Cohort 2)	PK: AUC[0-∞] of Omeprazole	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: Cmax of Omeprazole (Cohort 2)	PK: Cmax of Omeprazole	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: AUC[0-∞] of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2)	5-hydroxyomeprazole is a major metabolite of omeprazole.	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: Cmax of Omeprazole Metabolite: 5-hydroxyomeprazole (Cohort 2)	5-hydroxyomeprazole is a major metabolite of omeprazole.	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: AUC[0-∞] of Dextromethorphan (Cohort 2)	PK: AUC[0-∞] of Dextromethorphan	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: Cmax of Dextromethorphan (Cohort 2)	PK: Cmax of Dextromethorphan	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: Area Under the Concentration Versus Time Curve (AUC) From Time Zero to Tlast (AUC[0-tlast]) of Dextromethorphan Metabolite: Dextrorphan (Cohort 2)	Dextrorphan is a major metabolite of Dextromethorphan.	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: Cmax of Dextromethorphan Metabolite: Dextrorphan (Cohort 2)	Dextrorphan is a major metabolite of Dextromethorphan.	Day 1: Predose, 0.5, 1, 2, 3, 4, 6, 8,12, and 24 h postdose; Day 3: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 36, and 48 h postdose
PK: AUC[0-∞] of Imlunestrant (Cohort 3)	PK: AUC[0-∞] of Imlunestrant	Day 1 and Day 18: Predose, 1, 2, 3, 4, 5, 6 ,8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h post dose
PK: Cmax of Imlunestrant (Cohort 3)	PK: Cmax of Imlunestrant	Day 1 and Day 18: Predose, 1, 2, 3, 4, 5, 6 ,8, 12, 24, 36, 48, 72, 96, 120, 144, and 168 h post dose
PK: AUC[0-∞] of Rosuvastatin (Cohort 4)	PK: AUC[0-∞] of Rosuvastatin	Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
PK: Cmax of Rosuvastatin (Cohort 4)	PK: Cmax of Rosuvastatin	Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
PK: AUC[0-∞] of Digoxin (Cohort 4)	PK: AUC[0-∞] of Digoxin	Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose
PK: Cmax of Digoxin (Cohort 4)	PK: Cmax of Digoxin	Day 1: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, and 96 h post dose; Day 10: Predose, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, and 120 h post dose

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2022
• Primary Completion (Actual): November 2, 2022
• Study Completion (Actual): November 2, 2022

Study Registration Dates

• First Submitted: June 30, 2022
• First Submitted That Met QC Criteria: June 30, 2022
• First Posted (Actual): July 6, 2022

Study Record Updates

• Last Update Posted (Estimated): December 12, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 15, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Carbohydrates; Alkaloids; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Glycosides; Amides; Pyrimidines; Steroids; Fused-Ring Compounds; Hydrocarbons, Halogenated; Heterocyclic Compounds, 4 or More Rings; Quinolines; Sulfonamides; Sulfones; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Phenanthrenes; Fluorobenzenes; Hydrocarbons, Fluorinated; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Quinuclidines; Cinchona Alkaloids; Rosuvastatin Calcium; Digoxin; Omeprazole; Dextromethorphan; Quinidine; Imlunestrant; repaglinide
• Other Study ID Numbers: 18413; J2J-MC-JZLI (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