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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: LY3537982
* Drug: Digoxin
* Drug: Rosuvastatin
* Drug: Midazolam
* Drug: Midazolam


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3537982 + Digoxin & Rosuvastatin (Part 1)<br>Single oral doses of digoxin and rosuvastatin with or without multiple doses of LY3537982 administered orally | Drug: LY3537982<br>* Administered orally<br>Drug: Digoxin<br>* Administered orally<br>Drug: Rosuvastatin<br>* Administered orally<br>|
| Experimental: LY3537982 + Midazolam (Part 2)<br>Single doses of midazolam administered either orally or intravenously (IV) with or without multiple doses of LY3537982 administered orally | Drug: LY3537982<br>* Administered orally<br>Drug: Midazolam<br>* Administered orally<br>Drug: Midazolam<br>* Administered IV<br>|

What is the study measuring?
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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 |