A Study of Effect of Multiple Doses of LOXO-305 on the Pharmacokinetics of Single Oral Doses of CYP1A2, CYP2C9, CYP2C19 Substrates in Healthy Participants

A Phase I, Open-label, Fixed-sequence, Drug Interaction Study to Investigate the Effect of Multiple Oral Doses of LOXO-305 on CYP1A2, CYP2C9, and CYP2C19 Substrates Using a Probe Drug Cocktail in Healthy Subjects

The main purpose of this study is to evaluate the effect of LOXO-305 on single oral dose of caffeine cytochrome P450 1A2 (CYP1A2) substrate, S-warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate) when administered as multiple doses by collecting the blood samples and conducting the blood tests to measure how much LOXO-305 is in the bloodstream and how the body handles and eliminates LOXO-305 in adult healthy participants. The study will also evaluate the safety and tolerability of LOXO-305. The study will be conducted in two periods. Participants will stay in this study for up to 67 days, including screening.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Pirtobrutinib; Drug: Caffeine Tablet; Drug: Omeprazole capsule; Drug: Warfarin tablet

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75247
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Must have Body mass index (BMI) within the range of 18.0 to 32.0 kilograms per square meter (kg/m^2), inclusive.
• Male and female participants in good health, determined by no clinically significant findings from medical history, 12-lead Electrocardiogram (ECG), vital sign measurements, or clinical laboratory evaluations as assessed by the investigator.
• Female participants of non-childbearing potential and male participants who follow standard contraceptive methods.
• Must have comply with all study procedures, including the 23-night stay at the Clinical Research Unit (CRU) and follow-up phone call.

Exclusion Criteria:

• History or presence of any diseases or conditions of clinical significance by the Investigator (or designee) and/or Sponsor.
• Known ongoing alcohol and/or drug abuse within 2 years prior to Screening.
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Period 1: Probe Drug Cocktail; Participants received 200 milligrams (mg) caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet on Day 1.	Drug: Caffeine Tablet; Administered orally.; Drug: Omeprazole capsule; Administered orally.; Drug: Warfarin tablet; Administered orally.
Experimental: Period 2: Pirtobrutinib + Probe Drug Cocktail; Participants received oral dose of 200 mg Pirtobrutinib once daily (QD) from Day 6 to Day 19. On Day 15, Pirtobrutinib was co-administered with 200 mg caffeine tablet, 40 mg omeprazole capsule, and 10 mg warfarin tablet as a single dose of probe drug cocktail, along with 10 mg vitamin K tablet. There was a 5-day washout period between the probe drug cocktail on Day 1 (Period 1) and the first dose of Pirtobrutinib on Day 6 (Period 2).	Drug: Pirtobrutinib; Administered orally.; Other Names: LOXO-305; LY3527727; Drug: Caffeine Tablet; Administered orally.; Drug: Omeprazole capsule; Administered orally.; Drug: Warfarin tablet; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Caffeine	Area under the concentration time curve (AUC) from hour 0 to 24 hours post-dose (AUC0-24) of caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Paraxanthine	AUC0-24 of Paraxanthine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Omeprazole	AUC0-24 of Omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Warfarin	AUC(0-24) of Warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Pirtobrutinib	AUC0-24 of Pirtobrutinib was reported.	Period 2, Day 15 (0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours Post dose)
Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Caffeine	AUC from hour 0 to the last measurable concentration (AUC0-t) of caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Paraxanthine	AUC0-t of Paraxanthine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Omeprazole	AUC0-t of Omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Warfarin	AUC0-t of Warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Pirtobrutinib	AUC0-t of Pirtobrutinib was reported.	Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Caffeine	AUC from hour 0 extrapolated to infinity (AUC0-inf) of Caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Paraxanthine	AUC0-inf of Paraxanthine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Omeprazole	AUC0-inf of omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Warfarin	AUC0-inf of Warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Percentage Extrapolation for AUC0-inf (%AUCextrap): Caffeine	AUC0-inf (%AUCextrap) of caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Percentage Extrapolation for AUC0-inf (%AUCextrap): Paraxanthine	AUC0-inf (%AUCextrap) of Paraxanthine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Percentage Extrapolation for AUC0-inf (%AUCextrap): Omeprazole	%AUCextrap of omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Percentage Extrapolation for AUC0-inf (%AUCextrap): Warfarin	%AUCextrap of Warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Apparent Systemic Clearance (CL/F): Caffeine	CL/F for caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Apparent Systemic Clearance (CL/F): Omeprazole	CL/F of omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Apparent Systemic Clearance (CL/F): Warfarin	CL/F of warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Apparent Systemic Clearance (CL/F): Pirtobrutinib	CL/F of Pirtobrutinib was reported.	Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)
Maximum Observed Plasma Concentration (Cmax): Caffeine	Cmax of caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Maximum Observed Plasma Concentration (Cmax): Paraxanthine	Cmax of Paraxanthine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Maximum Observed Plasma Concentration (Cmax): Omeprazole	Cmax of omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Maximum Observed Plasma Concentration (Cmax): Warfarin	Cmax of warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Maximum Observed Plasma Concentration (Cmax): Pirtobrutinib	Cmax of Pirtobrutinib was reported.	Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)
Time to Maximum Observed Plasma Concentration (Tmax): Caffeine	Tmax of caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Time to Maximum Observed Plasma Concentration (Tmax): Paraxanthine	Tmax of Paraxanthine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Time to Maximum Observed Plasma Concentration (Tmax): Omeprazole	Tmax of omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Time to Maximum Observed Plasma Concentration (Tmax): Warfarin	Tmax of warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Time to Maximum Observed Plasma Concentration (Tmax): Pirtobrutinib	Tmax of Pirtobrutinib was reported.	Period 2, Day 15 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 192 hours postdose)
Apparent Terminal Elimination Rate Constant (λZ): Caffeine	λZ of caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Apparent Terminal Elimination Rate Constant (λZ): Paraxanthine	λZ of Paraxanthine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Apparent Terminal Elimination Rate Constant (λZ): Omeprazole	λZ of omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Apparent Terminal Elimination Rate Constant (λZ): Warfarin	λZ of warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Apparent Volume of Distribution at Terminal Phase (Vz/F): Caffeine	Vz/F of caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Apparent Volume of Distribution at Terminal Phase (Vz/F): Omeprazole	Vz/F of omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Apparent Volume of Distribution at Terminal Phase (Vz/F): Warfarin	Vz/F of Warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Metabolite to Parent Drug AUC Ratio (MRAUC): AUC Ratio of Paraxanthine to Caffeine	AUC Ratio of paraxanthine (Metabolite) to caffeine (Parent drug) was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Mean Residence Time (MRT): Caffeine	MRT of caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Mean Residence Time (MRT): Paraxanthine	MRT of Paraxanthine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Mean Residence Time (MRT): Omeprazole	MRT of omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Mean Residence Time (MRT): Warfarin	MRT of warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)
Apparent Terminal Elimination Half-Life (t1/2): Caffeine	t1/2 of caffeine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Apparent Terminal Elimination Half-Life (t1/2): Paraxanthine	t1/2 of Paraxanthine was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24 hours postdose)
Apparent Terminal Elimination Half-Life (t1/2): Omeprazole	t1/2 of omeprazole was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48 hours postdose)
Apparent Terminal Elimination Half-Life (t1/2): Warfarin	t1/2 of warfarin was reported.	Period 1, Day 1 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose); Period 2, Day 15 (Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours postdose)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Loxo Oncology, Inc.
• Investigators: Study Director: Renee Ward, MD, PhD, Loxo Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2021
• Primary Completion (Actual): April 15, 2021
• Study Completion (Actual): April 15, 2021

Study Registration Dates

• First Submitted: December 15, 2023
• First Submitted That Met QC Criteria: January 12, 2024
• First Posted (Actual): January 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 14, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Tyrosine Kinase Inhibitors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Enzyme Inhibitors; Protein Kinase Inhibitors; Neurotransmitter Agents; Purinergic Antagonists; Purinergic Agents; Central Nervous System Stimulants; Anticoagulants; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Anti-Ulcer Agents; Proton Pump Inhibitors; Pirtobrutinib; Warfarin; Caffeine; Omeprazole
• Other Study ID Numbers: LOXO-BTK-20010; J2N-OX-JZNE (Other Identifier: Eli Lilly and Company)

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