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A Study of Effect of Food and a Proton Pump Inhibitor on Selpercatinib (LY3527723) in Healthy Participants

An Open-Label, Randomized, Crossover Study to Evaluate the Effect of Food and a Proton Pump Inhibitor on the Single-Dose Pharmacokinetics of LOXO-292 in Healthy Adult Subjects

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05468164
Enrollment
20
Registered
2022-07-21
Start date
2018-05-31
Completion date
2018-09-13
Last updated
2025-09-19

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 assess the effect of food on how fast selpercatinib gets into the bloodstream and how long it takes the body to remove it after a high-fat meal, and the effect of a change in gastric pH after multiple doses of omeprazole on how fast selpercatinib gets into the bloodstream and how long it takes the body to remove it when administered under fasted and fed conditions in healthy participants. The study will also evaluate the safety and tolerability of selpercatinib in healthy participants. The study will last up to 33 days excluding the screening period.

Interventions

DRUGSelpercatinib

Administered orally

DRUGOmeprazole

Administered orally

Sponsors

Loxo Oncology, Inc.
CollaboratorINDUSTRY
Eli Lilly and Company
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes

Inclusion criteria

* Non-vasectomized, male participants must have agreed to use a condom with spermicide or abstain from sexual intercourse during the study until 6 months after the last dosing. (No restrictions were required for a vasectomized male provided his vasectomy had been performed 4 months or more prior to the first dosing of study drug) * If male, must have agreed not to donate sperm from the first dosing until 6 months after the last dosing * 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

* Had a history of gastritis, gastrointestinal tract or hepatic disorder or other clinical condition that might have, in the opinion of the Principal Investigator or designee, and as confirmed by the Sponsor, affected the absorption, distribution, biotransformation, or excretion of LOXO 292 or omeprazole

Design outcomes

Primary

MeasureTime frameDescription
Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of SelpercatinibDay 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 in Periods 1, 2, 3, and 4.PK: AUC0-t of Selpercatinib was reported.
PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of SelpercatinibDay 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 in Periods 1, 2, 3, and 4.PK: AUC0-inf of Selpercatinib was reported.
PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of SelpercatinibDay 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 in Periods 1, 2, 3, and 4.PK: AUC%extrap of Selpercatinib was reported.
PK: Maximum Observed Concentration (Cmax) of SelpercatinibDay 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 in Periods 1, 2, 3, and 4.PK: Cmax of Selpercatinib was reported.
PK: Time to Reach Cmax (Tmax) of SelpercatinibDay 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 in Periods 1, 2, 3, and 4.PK: Tmax of Selpercatinib was reported.
PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of SelpercatinibDay 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 in Periods 1, 2, 3, and 4.PK: Kel of Selpercatinib was reported.
PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of SelpercatinibDay 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 in Periods 1, 2, 3, and 4.PK: CL/F of Selpercatinib was reported.
PK: Apparent First-order Terminal Elimination Half-life (t½) of SelpercatinibDay 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 in Periods 1, 2, 3, and 4.PK: t½ of Selpercatinib was reported.

Countries

United States

Participant flow

Recruitment details

A total of 20 participants were enrolled in this study. Participants were randomly assigned to 1 of 4 treatment sequences (ABCD, ABDC, BACD, and BADC). Treatment A was a single oral dose of 160 milligrams (mg) selpercatinib under fasting condition, Treatment B was a single oral dose of 160 mg selpercatinib under fed condition, (contd.)

Pre-assignment details

(contd.) Treatment C was multiple daily oral doses of 40 mg omeprazole with a single oral dose of 160 mg selpercatinib co-administered under fasting conditions, and Treatment D was multiple daily oral doses of 40 mg omeprazole with 160 mg selpercatinib co-administered under fed condition.

Participants by arm

ArmCount
Treatment Sequence 1: ABCD
Participants received: * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 1 in fasted state. * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 2 in fed state. * Multiple daily oral doses of 40 mg omeprazole administered from Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 3 in fasted state. * Multiple daily oral doses of 40 mg omeprazole administered from Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 4 in fed state. Periods 1 and 2, 2 and 3 were separated by a 7-day washout period. There was no washout between Periods 3 and 4.
5
Treatment Sequence 2: ABDC
Participants received: * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 1 in fasted state. * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 2 in fed state. * Multiple daily oral doses of 40 mg omeprazole administered from Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 3 in fed state. * Multiple daily oral doses of 40 mg omeprazole administered from Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 4 in fasted state. Periods 1 and 2, 2 and 3 were separated by a 7-day washout period. There was no washout between Periods 3 and 4.
5
Treatment Sequence 3: BACD
Participants received: * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 1 in fed state. * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 2 in fasted state. * Multiple daily oral doses of 40 mg omeprazole administered from Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 3 in fasted state. * Multiple daily oral doses of 40 mg omeprazole administered from Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 4 in fed state. Periods 1 and 2, 2 and 3 were separated by a 7-day washout period. There was no washout between Periods 3 and 4.
5
Treatment Sequence 3: BADC
Participants received: * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 1 in fed state. * Single oral dose of 160 mg selpercatinib administered on Day 1 of Period 2 in fasted state. * Multiple daily oral doses of 40 mg omeprazole administered from Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 3 in fed state. * Multiple daily oral doses of 40 mg omeprazole administered from Day 1 to Day 7 along with single oral dose of 160 mg selpercatinib on Day 1 of Period 4 in fasted state. Periods 1 and 2, 2 and 3 were separated by a 7-day washout period. There was no washout between Periods 3 and 4.
5
Total20

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003
Treatment Period 4Adverse Event0001

Baseline characteristics

CharacteristicTreatment Sequence 1: ABCDTotalTreatment Sequence 3: BADCTreatment Sequence 3: BACDTreatment Sequence 2: ABDC
Age, Continuous45.0 years
STANDARD_DEVIATION 6.82
40.9 years
STANDARD_DEVIATION 7.82
38.4 years
STANDARD_DEVIATION 7.44
41.8 years
STANDARD_DEVIATION 10.35
38.2 years
STANDARD_DEVIATION 6.5
Ethnicity (NIH/OMB)
Hispanic or Latino
5 Participants19 Participants5 Participants5 Participants4 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
0 Participants1 Participants0 Participants0 Participants1 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants1 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
5 Participants19 Participants5 Participants5 Participants4 Participants
Region of Enrollment
United States
5 Participants20 Participants5 Participants5 Participants5 Participants
Sex: Female, Male
Female
3 Participants10 Participants3 Participants2 Participants2 Participants
Sex: Female, Male
Male
2 Participants10 Participants2 Participants3 Participants3 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
deaths
Total, all-cause mortality
0 / 200 / 200 / 190 / 20
other
Total, other adverse events
3 / 206 / 207 / 198 / 20
serious
Total, serious adverse events
0 / 200 / 200 / 190 / 20

Outcome results

Primary

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.

Time frame: 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 in Periods 1, 2, 3, and 4.

Population: All participants who received at least one dose of study drug and had evaluable PK data.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Treatment A: 160 mg Selpercatinib (Fasted)Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib26160 nanogram*hour per milliliter (ng*h/mL)Geometric Coefficient of Variation 38.9
Treatment B: 160 mg Selpercatinib (Fed)Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib28400 nanogram*hour per milliliter (ng*h/mL)Geometric Coefficient of Variation 20.4
Treatment C: 160 mg Selpercatinib + 40 mg Omeprazole (Fasted)Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib7973 nanogram*hour per milliliter (ng*h/mL)Geometric Coefficient of Variation 161.9
Treatment D: 160 mg Selpercatinib + 40 mg Omeprazole (Fed)Pharmacokinetics (PK): Area Under the Concentration-time Curve, From Time 0 to the Last Observed Non-zero Concentration (AUC0-t) of Selpercatinib26570 nanogram*hour per milliliter (ng*h/mL)Geometric Coefficient of Variation 14.1
Primary

PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib

PK: t½ of Selpercatinib was reported.

Time frame: 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 in Periods 1, 2, 3, and 4.

Population: All participants who received at least one dose of study drug and had evaluable PK data.

ArmMeasureValue (MEAN)Dispersion
Treatment A: 160 mg Selpercatinib (Fasted)PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib29.801 hStandard Deviation 6.6155
Treatment B: 160 mg Selpercatinib (Fed)PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib31.641 hStandard Deviation 6.5273
Treatment C: 160 mg Selpercatinib + 40 mg Omeprazole (Fasted)PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib37.288 hStandard Deviation 16.0167
Treatment D: 160 mg Selpercatinib + 40 mg Omeprazole (Fed)PK: Apparent First-order Terminal Elimination Half-life (t½) of Selpercatinib35.841 hStandard Deviation 14.717
Primary

PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib

PK: Kel of Selpercatinib was reported.

Time frame: 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 in Periods 1, 2, 3, and 4.

Population: All participants who received at least one dose of study drug and had evaluable PK data.

ArmMeasureValue (MEAN)Dispersion
Treatment A: 160 mg Selpercatinib (Fasted)PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib0.02445 1/hourStandard Deviation 0.0058755
Treatment B: 160 mg Selpercatinib (Fed)PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib0.02282 1/hourStandard Deviation 0.0047476
Treatment C: 160 mg Selpercatinib + 40 mg Omeprazole (Fasted)PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib0.02207 1/hourStandard Deviation 0.0095909
Treatment D: 160 mg Selpercatinib + 40 mg Omeprazole (Fed)PK: Apparent First Order Terminal Elimination Rate Constant (Kel) of Selpercatinib0.02214 1/hourStandard Deviation 0.0077557
Primary

PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib

PK: CL/F of Selpercatinib was reported.

Time frame: 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 in Periods 1, 2, 3, and 4.

Population: All participants who received at least one dose of study drug and had evaluable PK data.

ArmMeasureValue (MEAN)Dispersion
Treatment A: 160 mg Selpercatinib (Fasted)PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib6.585 Liters/hourStandard Deviation 3.2392
Treatment B: 160 mg Selpercatinib (Fed)PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib5.717 Liters/hourStandard Deviation 1.156
Treatment C: 160 mg Selpercatinib + 40 mg Omeprazole (Fasted)PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib50.45 Liters/hourStandard Deviation 135.82
Treatment D: 160 mg Selpercatinib + 40 mg Omeprazole (Fed)PK: Apparent Total Plasma Clearance After Oral (Extravascular) Administration (CL/F) of Selpercatinib6.031 Liters/hourStandard Deviation 0.8165
Primary

PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib

PK: AUC0-inf of Selpercatinib was reported.

Time frame: 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 in Periods 1, 2, 3, and 4.

Population: All participants who received at least one dose of study drug and had evaluable PK data.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Treatment A: 160 mg Selpercatinib (Fasted)PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib26280 ng*h/mLGeometric Coefficient of Variation 38.9
Treatment B: 160 mg Selpercatinib (Fed)PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib28530 ng*h/mLGeometric Coefficient of Variation 20.4
Treatment C: 160 mg Selpercatinib + 40 mg Omeprazole (Fasted)PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib8256 ng*h/mLGeometric Coefficient of Variation 143.3
Treatment D: 160 mg Selpercatinib + 40 mg Omeprazole (Fed)PK: Area Under the Concentration-time Curve, From Time 0 Extrapolated to Infinity (AUC0-inf) of Selpercatinib26770 ng*h/mLGeometric Coefficient of Variation 13.8
Primary

PK: Maximum Observed Concentration (Cmax) of Selpercatinib

PK: Cmax of Selpercatinib was reported.

Time frame: 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 in Periods 1, 2, 3, and 4.

Population: All participants who received at least one dose of study drug and had evaluable PK data.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Treatment A: 160 mg Selpercatinib (Fasted)PK: Maximum Observed Concentration (Cmax) of Selpercatinib2024 nanograms per milliliter (ng/mL)Geometric Coefficient of Variation 60.4
Treatment B: 160 mg Selpercatinib (Fed)PK: Maximum Observed Concentration (Cmax) of Selpercatinib1745 nanograms per milliliter (ng/mL)Geometric Coefficient of Variation 20.9
Treatment C: 160 mg Selpercatinib + 40 mg Omeprazole (Fasted)PK: Maximum Observed Concentration (Cmax) of Selpercatinib251.5 nanograms per milliliter (ng/mL)Geometric Coefficient of Variation 263.9
Treatment D: 160 mg Selpercatinib + 40 mg Omeprazole (Fed)PK: Maximum Observed Concentration (Cmax) of Selpercatinib1023 nanograms per milliliter (ng/mL)Geometric Coefficient of Variation 24.7
Primary

PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib

PK: AUC%extrap of Selpercatinib was reported.

Time frame: 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 in Periods 1, 2, 3, and 4.

Population: All participants who received at least one dose of study drug and had evaluable PK data.

ArmMeasureValue (MEAN)Dispersion
Treatment A: 160 mg Selpercatinib (Fasted)PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib0.4468 percentage of AUC0-inf extrapolatedStandard Deviation 0.14909
Treatment B: 160 mg Selpercatinib (Fed)PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib0.4541 percentage of AUC0-inf extrapolatedStandard Deviation 0.22
Treatment C: 160 mg Selpercatinib + 40 mg Omeprazole (Fasted)PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib3.065 percentage of AUC0-inf extrapolatedStandard Deviation 7.5841
Treatment D: 160 mg Selpercatinib + 40 mg Omeprazole (Fed)PK: Percent of AUC0-inf Extrapolated (AUC%Extrap) of Selpercatinib0.7158 percentage of AUC0-inf extrapolatedStandard Deviation 0.46382
Primary

PK: Time to Reach Cmax (Tmax) of Selpercatinib

PK: Tmax of Selpercatinib was reported.

Time frame: 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 in Periods 1, 2, 3, and 4.

Population: All participants who received at least one dose of study drug and had evaluable PK data.

ArmMeasureValue (MEDIAN)
Treatment A: 160 mg Selpercatinib (Fasted)PK: Time to Reach Cmax (Tmax) of Selpercatinib1.502 hours (h)
Treatment B: 160 mg Selpercatinib (Fed)PK: Time to Reach Cmax (Tmax) of Selpercatinib3.997 hours (h)
Treatment C: 160 mg Selpercatinib + 40 mg Omeprazole (Fasted)PK: Time to Reach Cmax (Tmax) of Selpercatinib2.501 hours (h)
Treatment D: 160 mg Selpercatinib + 40 mg Omeprazole (Fed)PK: Time to Reach Cmax (Tmax) of Selpercatinib6.011 hours (h)

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026