A Study of Selpercatinib (LY3527723) in Healthy Participants

A Phase I, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LOXO-292 in Healthy Adult Subjects

The main purpose of this study is to determine how safe and how well tolerated selpercatinib is when given as oral doses to healthy participants. The study will also assess how fast selpercatinib gets into the blood stream and how long it takes the body to remove it. The study will last up to about 6 weeks, inclusive of screening period.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 18
• 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:

• 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• Have previously participated or withdrawn from this study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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 320 mg Selpercatinib; Participants received a single oral dose of 320 mg selpercatinib on Day 1, preceded by an overnight fast of at least 10 hours, followed by a fast from food (not including water) for at least 4 hours post dose.	Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723
Experimental: 640 mg Selpercatinib; Participants received a single oral dose of 640 mg selpercatinib on Day 1, preceded by an overnight fast of at least 10 hours, followed by a fast from food (not including water) for at least 4 hours post dose.	Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723
Experimental: 720 mg Selpercatinib; Participants received a single oral dose of 720 mg selpercatinib on Day 1, preceded by an overnight fast of at least 10 hours, followed by a fast from food (not including water) for at least 4 hours post dose.	Drug: Selpercatinib; Administered orally.; Other Names: LOXO-292; LY3527723

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module.	Baseline up to Day 8

Secondary 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 is calculated using the linear trapezoidal with linear interpolation method.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose
PK: Area Under the Concentration-time Curve, From Time 0 to Hour 24 (AUC0-24) of Selpercatinib	PK: AUC0-24 was calculated using the linear trapezoidal with linear interpolation method.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib	PK: AUC0-inf was calculated as AUC0-inf = AUC0-t + (Clast/Kel) where Clast is the last observed/measured concentration and Kel is the apparent terminal elimination rate constant, which represents the fraction of drug eliminated per unit time.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose
PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib	PK: Percent of AUC0-inf extrapolated was calculated as (1-AUC0-t/AUC0-inf) *100.	Predose -168 hours post dose
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib	PK: CL/F was calculated as Dose/(AUC0-inf).	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose
PK: Maximum Observed Concentration (Cmax) of Selpercatinib	PK: Cmax was taken directly from bioanalytical data.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose
PK: Time to Reach Cmax (Tmax) of Selpercatinib	PK: Tmax was time to reach Cmax. If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value taken from clinical database as the difference in the time of administration and the time of the blood draw which is associated with the Cmax.	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose
PK: Apparent First-order Terminal Elimination Rate Constant (Kel) of Selpercatinib	PK: Apparent terminal elimination rate constant; represents the fraction of drug eliminated per unit time calculated by linear least squares regression analysis using the maximum number of points in the terminal log linear phase (e.g., three or more non zero plasma concentrations).	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose
PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Selpercatinib	PK: Vz/F calculated as Dose/(AUC0-inf x Kel).	Predose (within 30 minutes), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, 120, 144 and 168 hours postdose

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): February 12, 2019
• Primary Completion (Actual): March 12, 2019
• Study Completion (Actual): March 26, 2019

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): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 17485; J2G-OX-JZJF (Other Identifier: Eli Lilly and Company); LOXO-RET-18057 (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