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

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06111521
• Collaborator: Loxo Oncology, Inc. (Industry)
• Enrollment: 56
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 3.2
• Patients Per Site Per Month: 17.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: LY3537982; Drug: Digoxin; Drug: Rosuvastatin; Drug: Midazolam; Drug: Midazolam	Phase 1

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 56 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: 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
• Anticipated Study Start Date: Oct 27, 2023
• Anticipated Primary Completion Date: Jan 31, 2024
• Anticipated Study Completion Date: Jan 31, 2024

Arms and Interventions

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: LY3537982; Administered orally; Drug: Digoxin; Administered orally; Drug: Rosuvastatin; Administered orally
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: LY3537982; Administered orally; Drug: Midazolam; Administered orally; Drug: Midazolam; Administered IV

Outcome Measures

Primary Outcome Measures

1. Part 1: Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3537982 [Predose on day 11 up to day 17]

   Part 1: PK: Cmax of LY3537982

2. Part 1: PK: Area Under the Concentration-Time Curve (AUC) from Time 0 to Infinity (AUC[0-inf]) of LY3537982 [Predose on day 11 up to day 17]

   Part 1: PK: AUC[0-inf] of LY3537982

3. Part 1: PK: AUC from Time 0 to time of the last measurable concentration (AUClast) of LY3537982 [Predose on day 11 up to day 17]

   Part 1: PK: AUClast of LY3537982

4. Part 1: PK: Cmax of Digoxin [Predose on day 1 up to day 21]

   Part 1: PK: Cmax of Digoxin

5. Part 1: PK: AUC[0-inf] of Digoxin [Predose on day 1 up to day 21]

   Part 1: PK: AUC[0-inf] of Digoxin

6. Part 1: PK: AUClast of Digoxin [Predose on day 1 up to day 21]

   Part 1: PK: AUClast of Digoxin

7. Part 1: PK: Cmax of Rosuvastatin [Predose on day 1 up to day 21]

   Part 1: PK: Cmax of Rosuvastatin

8. Part 1: PK: AUC[0-inf] of Rosuvastatin [Predose on day 1 up to day 21]

   Part 1: PK: AUC[0-inf] of Rosuvastatin

9. Part 1: PK: AUClast of Rosuvastatin [Predose on day 1 up to day 21]

   Part 1: PK: AUClast of Rosuvastatin

10. Part 2: PK: Cmax of LY3537982 [Predose on day 4 up to day 11]

    Part 2: PK: Cmax of LY3537982

11. Part 2: PK: AUC[0-inf] of LY3537982 [Predose on day 4 up to day 11]

    Part 2: PK: AUC[0-inf] of LY3537982

12. Part 2: PK: AUClast of LY3537982 [Predose on day 4 up to day 11]

    Part 2: PK: AUClast of LY3537982

13. Part 2: PK: Cmax of Midazolam [Predose on day 1 up to day 9]

    Part 2: PK: Cmax of Midazolam

14. Part 2: PK: AUC[0-inf] of Midazolam [Predose on day 1 up to day 9]

    Part 2: PK: AUC[0-inf] of Midazolam

15. Part 2: PK: AUClast of Midazolam [Predose on day 1 up to day 9]

    Part 2: PK: AUClast of Midazolam

16. Part 2: PK: Cmax of 1'-Hydroxymidazolam [Predose on day 1 up to day 9]

    Part 2: PK: Cmax of 1'-Hydroxymidazolam

17. Part 2: PK: AUC[0-inf] of 1'-Hydroxymidazolam [Predose on day 1 up to day 9]

    Part 2: PK: AUC[0-inf] of 1'-Hydroxymidazolam

18. Part 2: PK: AUClast of 1'-Hydroxymidazolam [Predose on day 1 up to day 9]

    Part 2: PK: AUClast of 1'-Hydroxymidazolam

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	ICON Early Clinical & Bioanalytical Solutions	Salt Lake City	Utah	United States	84124

Sponsors and Collaborators

• Eli Lilly and Company
• Loxo Oncology, Inc.

Investigators

• Study Director: Yingying Guo-Avrutin, Loxo Oncology, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT06111521
• Other Study ID Numbers: LOXO-RAS-23007; J3M-OX-JZQJ
• First Posted: Nov 1, 2023
• Last Update Posted: Nov 1, 2023
• Last Verified: Oct 1, 2023

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Digoxin; Midazolam; Rosuvastatin Calcium

Study Results

No Results Posted as of Nov 1, 2023