A Drug-Drug Interaction Study of LY3537982 on Midazolam, Digoxin, and Rosuvastatin in Healthy Participants

A PHASE 1 STUDY TO EVALUATE THE EFFECTS OF MULTIPLE DOSES OF LY3537982 ON THE SINGLE-DOSE PHARMACOKINETICS OF MIDAZOLAM, DIGOXIN, AND ROSUVASTATIN IN HEALTHY ADULT SUBJECTS

The main purpose of this study is to evaluate the effects of multiple doses of LY3537982 on the pharmacokinetics (PK) of digoxin (a P-glycoprotein [P-gp] substrate), rosuvastatin (a breast cancer resistance protein [BCRP)] substrate), and midazolam (a substrate of Cytochrome P450 3A4 [CYP3A4]) in adult healthy participants. The study will also evaluate the safety and tolerability of LY3537982 with or without single doses of digoxin, rosuvastatin, and midazolam. The study is conducted in two parts. Participants will stay in the research center during the study, which will last about 23 and 11 days for part 1 and part 2, respectively, not including screening.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Rosuvastatin; Drug: Digoxin; Drug: Midazolam; Drug: LY3537982; Drug: Midazolam

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • ICON Early Clinical & Bioanalytical Solutions

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy status as defined by the absence of evidence of any clinically significant active or chronic disease
• Body mass index (BMI): 18.0 to 32.0 kilograms per square meter (kg/m²), inclusive

Exclusion Criteria:

• Females who are lactating or of childbearing potential
• Clinically significant history of any drug sensitivity, drug allergy, or food allergy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3537982 + Digoxin & Rosuvastatin (Part 1); Single oral doses of digoxin and rosuvastatin with or without multiple doses of LY3537982 administered orally	Drug: Rosuvastatin; Administered orally; Drug: Digoxin; Administered orally; Drug: LY3537982; Administered orally; Other Names: Olomorasib
Experimental: LY3537982 + Midazolam (Part 2); Single doses of midazolam administered either orally or intravenously (IV) with or without multiple doses of LY3537982 administered orally	Drug: Midazolam; Administered orally; Drug: LY3537982; Administered orally; Other Names: Olomorasib; Drug: Midazolam; Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3537982	Part 1: PK: Cmax of LY3537982	Predose on day 11 up to day 17
Part 1: PK: Area Under the Concentration-Time Curve (AUC) from Time 0 to Infinity (AUC[0-inf]) of LY3537982	Part 1: PK: AUC[0-inf] of LY3537982	Predose on day 11 up to day 17
Part 1: PK: AUC from Time 0 to time of the last measurable concentration (AUClast) of LY3537982	Part 1: PK: AUClast of LY3537982	Predose on day 11 up to day 17
Part 1: PK: Cmax of Digoxin	Part 1: PK: Cmax of Digoxin	Predose on day 1 up to day 21
Part 1: PK: AUC[0-inf] of Digoxin	Part 1: PK: AUC[0-inf] of Digoxin	Predose on day 1 up to day 21
Part 1: PK: AUClast of Digoxin	Part 1: PK: AUClast of Digoxin	Predose on day 1 up to day 21
Part 1: PK: Cmax of Rosuvastatin	Part 1: PK: Cmax of Rosuvastatin	Predose on day 1 up to day 21
Part 1: PK: AUC[0-inf] of Rosuvastatin	Part 1: PK: AUC[0-inf] of Rosuvastatin	Predose on day 1 up to day 21
Part 1: PK: AUClast of Rosuvastatin	Part 1: PK: AUClast of Rosuvastatin	Predose on day 1 up to day 21
Part 2: PK: Cmax of LY3537982	Part 2: PK: Cmax of LY3537982	Predose on day 4 up to day 11
Part 2: PK: AUC[0-inf] of LY3537982	Part 2: PK: AUC[0-inf] of LY3537982	Predose on day 4 up to day 11
Part 2: PK: AUClast of LY3537982	Part 2: PK: AUClast of LY3537982	Predose on day 4 up to day 11
Part 2: PK: Cmax of Midazolam	Part 2: PK: Cmax of Midazolam	Predose on day 1 up to day 9
Part 2: PK: AUC[0-inf] of Midazolam	Part 2: PK: AUC[0-inf] of Midazolam	Predose on day 1 up to day 9
Part 2: PK: AUClast of Midazolam	Part 2: PK: AUClast of Midazolam	Predose on day 1 up to day 9
Part 2: PK: Cmax of 1'-Hydroxymidazolam	Part 2: PK: Cmax of 1'-Hydroxymidazolam	Predose on day 1 up to day 9
Part 2: PK: AUC[0-inf] of 1'-Hydroxymidazolam	Part 2: PK: AUC[0-inf] of 1'-Hydroxymidazolam	Predose on day 1 up to day 9
Part 2: PK: AUClast of 1'-Hydroxymidazolam	Part 2: PK: AUClast of 1'-Hydroxymidazolam	Predose on day 1 up to day 9

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 27, 2023
• Primary Completion (Actual): April 1, 2024
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: October 27, 2023
• First Submitted That Met QC Criteria: October 27, 2023
• First Posted (Actual): November 1, 2023

Study Record Updates

• Last Update Posted (Estimated): November 8, 2024
• Last Update Submitted That Met QC Criteria: November 7, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anesthetics; Central Nervous System Depressants; Neurotransmitter Agents; Anti-Arrhythmia Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium; Midazolam; Digoxin
• Other Study ID Numbers: LOXO-RAS-23007; J3M-OX-JZQJ (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