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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05338515

Enrollment

Registered

2022-04-21

Start date

2019-02-12

Completion date

2019-03-26

Last updated

2025-05-18

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

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.

Interventions

DRUGSelpercatinib

Administered orally.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Yes

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days or any other type of medical research judged to be incompatible with this study * Have previously participated or withdrawn from this study * Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Baseline up to Day 8	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.

Secondary

Measure	Time frame	Description
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib	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: AUC0-t is calculated using the linear trapezoidal with linear interpolation method.
PK: Area Under the Concentration-time Curve, From Time 0 to Hour 24 (AUC0-24) of Selpercatinib	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: AUC0-24 was calculated using the linear trapezoidal with linear interpolation method.
PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib	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: 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.
PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib	Predose -168 hours post dose	PK: Percent of AUC0-inf extrapolated was calculated as (1-AUC0-t/AUC0-inf) \*100.
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib	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: CL/F was calculated as Dose/(AUC0-inf).
PK: Maximum Observed Concentration (Cmax) of Selpercatinib	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: Cmax was taken directly from bioanalytical data.
PK: Time to Reach Cmax (Tmax) of Selpercatinib	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: 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.
PK: Apparent First-order Terminal Elimination Rate Constant (Kel) of Selpercatinib	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 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).
PK: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Selpercatinib	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: Vz/F calculated as Dose/(AUC0-inf x Kel).

Countries

United States

Participant flow

Participants by arm

Arm	Count
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.	6
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.	6
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.	6
Total	18

Baseline characteristics

Characteristic	320 mg Selpercatinib	Total	720 mg Selpercatinib	640 mg Selpercatinib
Age, Continuous	37.8 years STANDARD_DEVIATION 7.19	37.9 years STANDARD_DEVIATION 8.91	39.3 years STANDARD_DEVIATION 9.99	36.7 years STANDARD_DEVIATION 10.69
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants	10 Participants	4 Participants	3 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants	8 Participants	2 Participants	3 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	1 Participants	3 Participants	1 Participants	1 Participants
Race (NIH/OMB) More than one race	1 Participants	3 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	12 Participants	4 Participants	4 Participants
Region of Enrollment United States	6 Participants	18 Participants	6 Participants	6 Participants
Sex: Female, Male Female	1 Participants	5 Participants	3 Participants	1 Participants
Sex: Female, Male Male	5 Participants	13 Participants	3 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 6	0 / 6
other Total, other adverse events	1 / 6	1 / 6	4 / 6
serious Total, serious adverse events	0 / 6	0 / 6	0 / 6

Outcome results

Primary

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.

Time frame: Baseline up to Day 8

Population: All randomized participants who received at least one dose of study drug and had at least one post dose safety assessment.

Arm	Measure	Value (NUMBER)
320 mg Selpercatinib	Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	0 participants
640 mg Selpercatinib	Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	0 participants
720 mg Selpercatinib	Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	0 participants

Secondary

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.

Time frame: 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