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Study of the Effect of Food and a Proton Pump Inhibitor (PPI; Omeprazole) on LOXO-305 in Healthy Participants

A Phase 1, Open Label, Randomized, 2-Way Crossover, 3-Period Study to Evaluate the Effect of Food and a Proton Pump Inhibitor on the Pharmacokinetics of LOXO-305 in Healthy Adult Subjects

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05134350
Enrollment
10
Registered
2021-11-24
Start date
2020-02-06
Completion date
2020-03-23
Last updated
2025-01-10

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

Conditions

Healthy Volunteers

Brief summary

The main purpose of this study is to learn about how food and a PPI (omeprazole) affect LOXO-305 in healthy participants. Participation could last about nine weeks.

Interventions

DRUGLOXO-305

LOXO-305 orally.

DRUGOmeprazole

Omeprazole Orally.

Sponsors

Loxo Oncology, Inc.
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

* Males and females of non-childbearing potential. * Within body mass index (BMI) range 18.0 to 32.0 kilograms per square meter (kg/m²). * Participants will be in good general health, based on medical history, physical examination findings, vital signs, 12 lead electrocardiogram (ECG), or clinical laboratory tests, as determined by the Investigator (or designee). * Able to comply with all study procedures, including the 25-night stay at the Clinical Research Unit and follow-up phone call.

Exclusion criteria

* History or presence of any of the following, deemed clinically significant by the Investigator (or designee), and/or Sponsor: * liver disease * pancreatitis * peptic ulcer disease * intestinal malabsorption * gastric reduction surgery * history or presence of clinically significant cardiovascular disease. * Participants with out-of-range, at-rest vital signs. * Abnormal laboratory values determined to be clinically significant by the Investigator (or designee), and Sponsor. * Clinically significant abnormality, as determined by the Investigator (or designee), from physical examination. * Participation in any other investigational study drug trial involving administration of any investigational drug in the past 30 days or 5 half-lives, whichever was longer, prior to the first dose administration (Day 1). * Use or intention to use any prescription or over-the-counter medications within 14 days prior to the first dose administration (Day 1) through the end of the trial. * History or presence, upon clinical evaluation, of any illness that, in the opinion of the Investigator, would interfere with the ability to provide informed consent or comply with study instructions, or that might confound the interpretation of the study results, or put the participant at undue risk. * Donation of blood from 56 days prior to Screening, plasma or platelets from 4 weeks prior to Screening. * Receipt of blood products within 2 months prior to Check-in (Day -1). * Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, biliary, renal, hematological, pulmonary, cardiovascular (including any prior history of cardiomyopathy or cardiac failure), GI, neurological, or psychiatric disorder (as determined by the Investigator), or cancer within the past 5 years (except localized basal cell, squamous, or in situ cancer of the skin).

Design outcomes

Primary

MeasureTime frameDescription
Pharmacokinetics (PK): Area Under the Concentration-time Curve From Hour 0 to 24 (AUC [0-24]) Hours of LOXO-305Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post LOXO-305 dosePK: AUC(0-24) hours of LOXO-305 is reported. AUC(0-24) was calculated by the linear trapezoidal method.
PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of LOXO-305Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePK: AUC(0-t) of LOXO-305 is reported. AUC(0-t) was calculated by linear trapezoidal method.
PK: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC[0-Inf]) of LOXO-305Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePK: AUC(0-inf) of LOXO-305 is reported. AUC(0-inf) was calculated using the formula: AUC(0-inf) = AUC(0-t) + Ct/λZ; where Ct is the last measurable concentration and λZ is the apparent terminal elimination rate constant.
PK: Percentage Extrapolation for AUC0-Inf (%AUCextrap) of LOXO-305Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePK: %AUCextrap of LOXO-305 is reported.
PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePK: Cmax of LOXO-305 is reported.
PK: Time to Maximum Observed Plasma Concentration (Tmax) of LOXO-305Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePK: tmax of LOXO-305 is reported.
PK: Apparent Terminal Elimination Half-life (t½) of LOXO-305Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePK: t½ of LOXO-305 is reported.
PK: Apparent Systemic Clearance (CL/F) of LOXO-305Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dosePK: CL/F of LOXO-305 is reported.

Countries

United States

Participant flow

Recruitment details

Participants were randomized to 2 treatment sequences (ABC and BAC), with each sequence having 3 periods where participants were crossed over between the periods in each sequence. A washout period of 7 days was maintained between each treatment period.

Participants by arm

ArmCount
Treatment Sequence 1: ABC
* Period 1: Single oral dose of 200 mg LOXO-305 (Fasted state) on Day 1 (Treatment A) * Period 2: Single oral dose of 200 mg LOXO-305 (Fed state) on Day 8 (Treatment B) * Period 3: Single oral dose of 40 mg Omeprazole (Fasted state) on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole (Fasted state) on Day 18 (Treatment C) A washout period of 7 days was maintained between each treatment period.
5
Treatment Sequence 2: BAC
* Period 1: Single oral dose of 200 mg LOXO-305 (Fed state) on Day 1 (Treatment B) * Period 2: Single oral dose of 200 mg LOXO-305 (Fasted state) on Day 8 (Treatment A) * Period 3: Single oral dose of 40 mg Omeprazole (Fasted state) on Day 15 to 17 and single oral dose of 200 mg LOXO-305 + 40 mg Omeprazole (Fasted state) on Day 18 (Treatment C) A washout period of 7 days was maintained between each treatment period.
5
Total10

Baseline characteristics

CharacteristicTreatment Sequence 1: ABCTotalTreatment Sequence 2: BAC
Age, Continuous43.2 years
STANDARD_DEVIATION 10.66
39.2 years
STANDARD_DEVIATION 8.88
35.2 years
STANDARD_DEVIATION 4.87
Ethnicity (NIH/OMB)
Hispanic or Latino
3 Participants6 Participants3 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
2 Participants4 Participants2 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
1 Participants2 Participants1 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
4 Participants8 Participants4 Participants
Region of Enrollment
United States
5 Participants10 Participants5 Participants
Sex: Female, Male
Female
1 Participants3 Participants2 Participants
Sex: Female, Male
Male
4 Participants7 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 / 100 / 100 / 100 / 10
other
Total, other adverse events
0 / 101 / 100 / 100 / 10
serious
Total, serious adverse events
0 / 100 / 100 / 100 / 10

Outcome results

Primary

Pharmacokinetics (PK): Area Under the Concentration-time Curve From Hour 0 to 24 (AUC [0-24]) Hours of LOXO-305

PK: AUC(0-24) hours of LOXO-305 is reported. AUC(0-24) was calculated by the linear trapezoidal method.

Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post LOXO-305 dose

Population: All participants who received at least one dose of LOXO-305 and had evaluable PK data.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Treatment A: 200 mg LOXO-305 (Fasted)Pharmacokinetics (PK): Area Under the Concentration-time Curve From Hour 0 to 24 (AUC [0-24]) Hours of LOXO-30555100 hour*nanograms per milliliterGeometric Coefficient of Variation 17.5
Treatment B: 200 mg LOXO-305 (Fed)Pharmacokinetics (PK): Area Under the Concentration-time Curve From Hour 0 to 24 (AUC [0-24]) Hours of LOXO-30551900 hour*nanograms per milliliterGeometric Coefficient of Variation 12.8
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)Pharmacokinetics (PK): Area Under the Concentration-time Curve From Hour 0 to 24 (AUC [0-24]) Hours of LOXO-30559900 hour*nanograms per milliliterGeometric Coefficient of Variation 15.5
Primary

PK: Apparent Systemic Clearance (CL/F) of LOXO-305

PK: CL/F of LOXO-305 is reported.

Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dose

Population: All participants who received at least one dose of LOXO-305 and had evaluable PK data.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Treatment A: 200 mg LOXO-305 (Fasted)PK: Apparent Systemic Clearance (CL/F) of LOXO-3052.22 Liter per Hours (L/h)Geometric Coefficient of Variation 17.6
Treatment B: 200 mg LOXO-305 (Fed)PK: Apparent Systemic Clearance (CL/F) of LOXO-3052.32 Liter per Hours (L/h)Geometric Coefficient of Variation 18.9
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)PK: Apparent Systemic Clearance (CL/F) of LOXO-3051.99 Liter per Hours (L/h)Geometric Coefficient of Variation 16.8
Primary

PK: Apparent Terminal Elimination Half-life (t½) of LOXO-305

PK: t½ of LOXO-305 is reported.

Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dose

Population: All participants who received at least one dose of LOXO-305 and had evaluable PK data.

ArmMeasureValue (MEAN)Dispersion
Treatment A: 200 mg LOXO-305 (Fasted)PK: Apparent Terminal Elimination Half-life (t½) of LOXO-30520.2 hoursStandard Deviation 4.24
Treatment B: 200 mg LOXO-305 (Fed)PK: Apparent Terminal Elimination Half-life (t½) of LOXO-30521.5 hoursStandard Deviation 5.75
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)PK: Apparent Terminal Elimination Half-life (t½) of LOXO-30519.7 hoursStandard Deviation 2.87
Primary

PK: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC[0-Inf]) of LOXO-305

PK: AUC(0-inf) of LOXO-305 is reported. AUC(0-inf) was calculated using the formula: AUC(0-inf) = AUC(0-t) + Ct/λZ; where Ct is the last measurable concentration and λZ is the apparent terminal elimination rate constant.

Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dose

Population: All participants who received at least one dose of LOXO-305 and had evaluable PK data.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Treatment A: 200 mg LOXO-305 (Fasted)PK: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC[0-Inf]) of LOXO-30590200 hour*nanograms per milliliterGeometric Coefficient of Variation 17.6
Treatment B: 200 mg LOXO-305 (Fed)PK: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC[0-Inf]) of LOXO-30586100 hour*nanograms per milliliterGeometric Coefficient of Variation 18.9
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)PK: Area Under the Concentration-time Curve Extrapolated to Infinity (AUC[0-Inf]) of LOXO-305101000 hour*nanograms per milliliterGeometric Coefficient of Variation 16.8
Primary

PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of LOXO-305

PK: AUC(0-t) of LOXO-305 is reported. AUC(0-t) was calculated by linear trapezoidal method.

Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dose

Population: All participants who received at least one dose of LOXO-305 and had evaluable PK data.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Treatment A: 200 mg LOXO-305 (Fasted)PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of LOXO-30589400 hour*nanograms per milliliterGeometric Coefficient of Variation 17.8
Treatment B: 200 mg LOXO-305 (Fed)PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of LOXO-30585100 hour*nanograms per milliliterGeometric Coefficient of Variation 19.3
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)PK: Area Under the Concentration-time Curve From Hour 0 to the Last Measurable Concentration (AUC[0-t]) of LOXO-30599600 hour*nanograms per milliliterGeometric Coefficient of Variation 17.1
Primary

PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305

PK: Cmax of LOXO-305 is reported.

Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dose

Population: All participants who received at least one dose of LOXO-305 and had evaluable PK data.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Treatment A: 200 mg LOXO-305 (Fasted)PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-3055450 nanograms per milliliterGeometric Coefficient of Variation 31.7
Treatment B: 200 mg LOXO-305 (Fed)PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-3054340 nanograms per milliliterGeometric Coefficient of Variation 16.6
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-3055490 nanograms per milliliterGeometric Coefficient of Variation 16.7
Primary

PK: Percentage Extrapolation for AUC0-Inf (%AUCextrap) of LOXO-305

PK: %AUCextrap of LOXO-305 is reported.

Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dose

Population: All participants who received at least one dose of LOXO-305 and had evaluable PK data.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Treatment A: 200 mg LOXO-305 (Fasted)PK: Percentage Extrapolation for AUC0-Inf (%AUCextrap) of LOXO-3050.911 percentage of extrapolationGeometric Coefficient of Variation 27.2
Treatment B: 200 mg LOXO-305 (Fed)PK: Percentage Extrapolation for AUC0-Inf (%AUCextrap) of LOXO-3051.12 percentage of extrapolationGeometric Coefficient of Variation 42.6
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)PK: Percentage Extrapolation for AUC0-Inf (%AUCextrap) of LOXO-3050.893 percentage of extrapolationGeometric Coefficient of Variation 34.5
Primary

PK: Time to Maximum Observed Plasma Concentration (Tmax) of LOXO-305

PK: tmax of LOXO-305 is reported.

Time frame: Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, and 168 hours post LOXO-305 dose

Population: All participants who received at least one dose of LOXO-305 and had evaluable PK data.

ArmMeasureValue (MEDIAN)
Treatment A: 200 mg LOXO-305 (Fasted)PK: Time to Maximum Observed Plasma Concentration (Tmax) of LOXO-3052.50 hours
Treatment B: 200 mg LOXO-305 (Fed)PK: Time to Maximum Observed Plasma Concentration (Tmax) of LOXO-3053.00 hours
Treatment C: 200 mg LOXO-305 + 40 mg Omeprazole (Fasted)PK: Time to Maximum Observed Plasma Concentration (Tmax) of LOXO-3052.25 hours

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