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

Phase 1

Completed

Conditions: Healthy Volunteers

Interventions: Drug: LOXO-305
Drug: Omeprazole

Registration Number: NCT05134350

Lead Sponsor: Loxo Oncology, Inc.

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment Sequence 1: ABC	Omeprazole	* Period 1: Single oral dose of 200 milligram (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.
Treatment Sequence 2: BAC	Omeprazole	* 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.
Treatment Sequence 1: ABC	LOXO-305	* Period 1: Single oral dose of 200 milligram (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.
Treatment Sequence 2: BAC	LOXO-305	* 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.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration-time Curve From Hour 0 to 24 (AUC [0-24]) Hours of LOXO-305	Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours post LOXO-305 dose	PK: 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-305	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	PK: 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-305	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	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.
PK: Percentage Extrapolation for AUC0-Inf (%AUCextrap) of LOXO-305	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	PK: %AUCextrap of LOXO-305 is reported.
PK: Maximum Observed Plasma Concentration (Cmax) of LOXO-305	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	PK: Cmax of LOXO-305 is reported.
PK: Time to Maximum Observed Plasma Concentration (Tmax) of LOXO-305	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	PK: tmax of LOXO-305 is reported.
PK: Apparent Terminal Elimination Half-life (t½) of LOXO-305	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	PK: t½ of LOXO-305 is reported.
PK: Apparent Systemic Clearance (CL/F) of LOXO-305	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	PK: CL/F of LOXO-305 is reported.