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

NCT06111521 | Completed Phase 1 FDA Drug

• 2 other identifiers: LOXO-RAS-23007J3M-OX-JZQJ
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (18)

• 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

Study Arms (2)

LY3537982 + Digoxin & Rosuvastatin (Part 1)

EXPERIMENTAL

Single oral doses of digoxin and rosuvastatin with or without multiple doses of LY3537982 administered orally

Drug: LY3537982; Drug: Digoxin; Drug: Rosuvastatin

LY3537982 + Midazolam (Part 2)

EXPERIMENTAL

Single doses of midazolam administered either orally or intravenously (IV) with or without multiple doses of LY3537982 administered orally

Drug: LY3537982; Drug: Midazolam

Interventions

LY3537982 DRUG

Administered orally

Also known as: Olomorasib

LY3537982 + Digoxin & Rosuvastatin (Part 1); LY3537982 + Midazolam (Part 2)

Digoxin DRUG

Administered orally

LY3537982 + Digoxin & Rosuvastatin (Part 1)

Rosuvastatin DRUG

Administered orally

LY3537982 + Digoxin & Rosuvastatin (Part 1)

Midazolam DRUG

Administered orally

LY3537982 + Midazolam (Part 2)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (1)

ICON Early Clinical & Bioanalytical Solutions

Salt Lake City, Utah, 84124, United States

Location

MeSH Terms

Interventions

Digoxin; Rosuvastatin Calcium; Midazolam

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Yingying Guo-Avrutin

  Loxo Oncology, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2023
• First Posted: November 1, 2023
• Study Start: October 27, 2023
• Primary Completion: April 1, 2024
• Study Completion: April 1, 2024
• Last Updated: November 8, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)