A Study of Effects of Selpercatinib (LY3527723) on Midazolam in Healthy Participants

An Open-Label, Fixed-Sequence Study to Evaluate the Effect of Multiple Doses of LOXO-292 on the Single Dose Pharmacokinetics of Midazolam in Healthy Adult Subjects

The main purpose of this study is to assess the effect of selpercatinib on how fast midazolam gets into the blood stream and how long it takes the body to remove it when administered in healthy participants. Information about safety and tolerability will be collected. The study will last up to about 6 weeks, inclusive of screening period.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Midazolam; Drug: Selpercatinib

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria :

• Male and female participants of non-childbearing potential who are agreeable to take birth control measures until study completion
• Body mass index (BMI) ≥ 18.0 and ≤ 32.0 kilograms per meter squared (kg/m²) and had a minimum weight of at least 50 kg at screening
• Have normal blood pressure, pulse rate, electrocardiogram (ECG), and blood and urine laboratory test results that are acceptable for the study

Exclusion Criteria:

• Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study
• Have previously participated or withdrawn from this study
• Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study
• Had blood loss of more than 500 milliliters (mL) within the previous 30 days of study screening
• Require treatment with inducers or inhibitors of cytochrome P450 (CYP) CYP3A within 14 days before the first dose of study drug through the end of Period 2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1: Midazolam; Day 1: Participants received single oral dose of 2 milligram (mg) midazolam syrup.	Drug: Midazolam; Administered orally.
Experimental: Period 2: Selpercatinib + Midazolam; Day 1 to Day 9: Participants received 160 mg Selpercatinib capsules twice daily (BID).; Day 10: Participant received 160 mg Selpercatinib capsules BID co-administered with a single oral dose of 2 mg midazolam syrup on the morning of Day 10.	Drug: Midazolam; Administered orally.; Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Midazolam and Its Metabolite 1-hydroxymidazolam (1-OH-midazolam)	PK: PK: AUC0-t of midazolam and its metabolite 1-OH-midazolam was reported.	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Midazolam and Its Metabolite 1-OH-midazolam	PK: PK: AUC0-inf of midazolam and its metabolite 1-OH-midazolam was reported.	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Midazolam and Its Metabolite 1-OH-midazolam	PK: PK: AUC%extrap of midazolam and its metabolite 1-OH-midazolam was reported.	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Maximum Observed Concentration (Cmax) of Midazolam and Its Metabolite 1-OH-midazolam	PK: Cmax of midazolam and its metabolite 1-OH-midazolam was reported.	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Time to Reach Maximum Observed Concentration (Tmax) of Midazolam and Its Metabolite 1-OH-midazolam	PK: Tmax of midazolam and its metabolite 1-OH-midazolam was reported.	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Apparent Terminal Elimination Rate Constant (Kel) of Midazolam and Its Metabolite 1-OH-midazolam	PK: Kel of midazolam and its metabolite 1-OH-midazolam was reported.	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Apparent Terminal Elimination Half-life (t½) of Midazolam and Its Metabolite 1-OH-midazolam	PK: t½ of midazolam and its metabolite 1-OH-midazolam was reported.	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Midazolam	PK: CL/F of midazolam was reported.	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Midazolam	PK: Vz/F of midazolam was reported.	Period 1: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose); Period 2: Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK: Area Under the Concentration-time Curve, From Time 0 to the 12 Hour (AUC0-12) of Selpercatinib	PK: AUC0-12 of Selpercatinib was reported.	Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose)
PK: Area Under the Concentration-time Curve During a Dosing Interval (Tau) at Steady State (AUCtau) of Selpercatinib	PK: AUC0-tau of Selpercatinib was reported.	Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Maximum Observed Concentration (Cmax) of Selpercatinib	PK: Cmax of Selpercatinib was reported.	Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose)
PK: Maximum Observed Concentration at Steady-state (Cmax,ss) of Selpercatinib	PK: Cmax,ss of Selpercatinib was reported.	Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Concentration Observed at the End of the Dosing Interval (Ctrough) of Selpercatinib	PK: Ctrough of Selpercatinib was reported.	Period 2: Predose at Day 1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Day 8, Day 9
PK: Time to Reach Maximum Observed Concentration (Tmax) of Selpercatinib	PK: tmax of Selpercatinib was reported.	Period 2: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose)
PK: Time to Reach Maximum Observed Concentration at Steady-state (Tmax,ss) of Selpercatinib	PK: Tmax,ss of Selpercatinib was reported.	Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)
PK: Apparent Total Plasma Clearance at Steady State After Oral/Extravascular Administration (CL,ss/F) of Selpercatinib	PK: CL,ss/F of Selpercatinib was reported.	Period 2: Day 9 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12 hours post dose); Day 10 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 hours post dose)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Loxo Oncology, Inc.
• 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 12, 2018
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): September 18, 2018

Study Registration Dates

• First Submitted: April 19, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Actual): October 20, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Benzodiazepines; Midazolam; selpercatinib
• Other Study ID Numbers: 17753; J2G-OX-JZJR (Other Identifier: Eli Lilly and Company); LOXO-RET-18017 (Other Identifier: Loxo Oncology, Inc.)

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