A Study of Effects of Itraconazole and Rifampin on Selpercatinib (LY3527723) in Healthy Participants

A 2-Part, Open-Label, Fixed-Sequence Study to Evaluate the Effects of Multiple Doses of Itraconazole and Rifampin on the Single-Dose Pharmacokinetics of LOXO-292 in Healthy Adult Subjects

The main purpose of this study is to assess the effect of itraconazole and rifampin on how fast selpercatinib 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 is conducted in two parts and it will last up to 54 days (part 1) and 59 days (part 2), respectively, inclusive of screening period.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 24
• 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: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 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• Have previously participated or withdrawn from this study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: Part 1 - 160 mg Selpercatinib + 200 mg Itraconazole; Participants received a single oral dose of 160 milligrams (mg) selpercatinib on Day 1 of Period 1. In Period 2, participants received an oral dose of 200 mg itraconazole administered once daily (QD) for 11 consecutive days (Days -4 to 7) with a single oral dose of 160 mg selpercatinib co-administered on Day 1 of Period 2. There was a washout period of at least 7 days between the dose of selpercatinib in Period 1 and the first dose of itraconazole in Period 2.	Drug: Itraconazole; Administered orally.; Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723
Experimental: Part 2 - 160 mg Selpercatinib + 600 mg Rifampin; Participants received a single oral dose of 160 mg selpercatinib on Day 1 of Period 1. In Period 2, participants received an oral dose of 600 mg rifampin administered QD for 16 consecutive days (Days 1 to 16) with a single oral dose of 160 mg selpercatinib co-administered on Day 1 and Day 10 of Period 2. There was a washout period of at least 7 days between the dose of selpercatinib in Period 1 and the first dose of rifampin and selpercatinib in Period 2.	Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723; Drug: Rifampin; Administered orally.

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 Selpercatinib	PK: AUC0-t of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. (contd.)	(contd.) Part 2, Period 2: (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post dose; (Day 10) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose.
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib	PK: AUC0-inf of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. (contd.)	(contd.) Part 2, Period 2: (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post dose; (Day 10) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose.
PK: Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib	PK: AUC%extrap of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. (contd.)	(contd.) Part 2, Period 2: (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post dose; (Day 10) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose.
PK: Maximum Observed Concentration (Cmax) of Selpercatinib	PK: Maximum observed concentration (Cmax) of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose.	(contd.) Part 2, Period 2: (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post dose; (Day 10) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose.
PK: Time to Reach Cmax (Tmax) of Selpercatinib	PK: Tmax of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. (contd.)	(contd.) Part 2, Period 2: (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post dose; (Day 10) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose.
PK: Apparent First-order Terminal Elimination Rate Constant (Kel) of Selpercatinib	PK: Kel of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. (contd.)	(contd.) Part 2, Period 2: (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post dose; (Day 10) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose.
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib	PK: CL/F of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. (contd.)	(contd.) Part 2, Period 2: (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post dose; (Day 10) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose.
PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib	PK: t½ of Selpercatinib was reported. Outcome measure timeframe: Parts 1 and 2, Period 1: (Day 1) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. Part 1, Period 2; (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose. (contd.)	(contd.) Part 2, Period 2: (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post dose; (Day 10) Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hours post dose.
Part 2 - PK: Area Under the Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24) of Selpercatinib Post Dose Day 1	PK: AUC0-24 of Selpercatinib in Part 2 was reported.	Part 2, Periods 1 and 2: (Day 1) pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 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): May 11, 2018
• Primary Completion (Actual): July 28, 2018
• Study Completion (Actual): August 22, 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 (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: August 29, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Azoles; Polycyclic Compounds; Heterocyclic Compounds, 4 or More Rings; Rifamycins; Lactams, Macrocyclic; Macrocyclic Compounds; Triazoles; Piperazines; Rifampin; Itraconazole; selpercatinib
• Other Study ID Numbers: 17751; J2G-OX-JZJP (Other Identifier: Eli Lilly and Company); LOXO-RET-18014 (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