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

Eli Lilly and Company16 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

Caffeine Tablet

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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).

Outcomes

Primary Outcomes

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.

Time frame: 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.

Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Omeprazole

AUC0-24 of Omeprazole was reported.

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.

Area Under the Concentration Time Curve (AUC) From Hour 0 to 24 Hours Post-Dose (AUC0-24): Pirtobrutinib

AUC0-24 of Pirtobrutinib was reported.

Time frame: 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.

Area Under the Concentration-time Curve (AUC), From Hour 0 to the Last Measurable Concentration (AUC0-t): Paraxanthine

AUC0-t of Paraxanthine was reported.

Area Under the Concentration Time Curve (AUC) From Hour 0 to the Last Measurable Concentration (AUC0-t): Omeprazole

AUC0-t of Omeprazole was reported.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Paraxanthine

AUC0-inf of Paraxanthine was reported.

Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Omeprazole

AUC0-inf of omeprazole was reported.

Area Under the Concentration Time Curve (AUC) From Hour 0 Extrapolated to Infinity (AUC0-inf): Warfarin

AUC0-inf of Warfarin was reported.

Percentage Extrapolation for AUC0-inf (%AUCextrap): Caffeine

AUC0-inf (%AUCextrap) of caffeine was reported.

Percentage Extrapolation for AUC0-inf (%AUCextrap): Paraxanthine

AUC0-inf (%AUCextrap) of Paraxanthine was reported.

Percentage Extrapolation for AUC0-inf (%AUCextrap): Omeprazole

%AUCextrap of omeprazole was reported.

Percentage Extrapolation for AUC0-inf (%AUCextrap): Warfarin

%AUCextrap of Warfarin was reported.

Apparent Systemic Clearance (CL/F): Caffeine

CL/F for caffeine was reported.

Apparent Systemic Clearance (CL/F): Omeprazole

CL/F of omeprazole was reported.

Apparent Systemic Clearance (CL/F): Warfarin

CL/F of warfarin was reported.

Apparent Systemic Clearance (CL/F): Pirtobrutinib

CL/F of Pirtobrutinib was reported.

Time frame: 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.

Maximum Observed Plasma Concentration (Cmax): Paraxanthine

Cmax of Paraxanthine was reported.

Time frame: 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.

Maximum Observed Plasma Concentration (Cmax): Warfarin

Cmax of warfarin was reported.

Maximum Observed Plasma Concentration (Cmax): Pirtobrutinib

Cmax of Pirtobrutinib was reported.

Time frame: 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.

Time to Maximum Observed Plasma Concentration (Tmax): Paraxanthine

Tmax of Paraxanthine was reported.

Time to Maximum Observed Plasma Concentration (Tmax): Omeprazole

Tmax of omeprazole was reported.

Time to Maximum Observed Plasma Concentration (Tmax): Warfarin

Tmax of warfarin was reported.

Time to Maximum Observed Plasma Concentration (Tmax): Pirtobrutinib

Tmax of Pirtobrutinib was reported.

Time frame: 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.

Apparent Terminal Elimination Rate Constant (λZ): Paraxanthine

λZ of Paraxanthine was reported.

Apparent Terminal Elimination Rate Constant (λZ): Omeprazole

λZ of omeprazole was reported.

Apparent Terminal Elimination Rate Constant (λZ): Warfarin

λZ of warfarin was reported.

Apparent Volume of Distribution at Terminal Phase (Vz/F): Caffeine

Vz/F of caffeine was reported.

Apparent Volume of Distribution at Terminal Phase (Vz/F): Omeprazole

Vz/F of omeprazole was reported.

Apparent Volume of Distribution at Terminal Phase (Vz/F): Warfarin

Vz/F of Warfarin was reported.

Metabolite to Parent Drug AUC Ratio (MRAUC): AUC Ratio of Paraxanthine to Caffeine

AUC Ratio of paraxanthine (Metabolite) to caffeine (Parent drug) was reported.

Mean Residence Time (MRT): Caffeine

MRT of caffeine was reported.

Mean Residence Time (MRT): Paraxanthine

MRT of Paraxanthine was reported.

Mean Residence Time (MRT): Omeprazole

MRT of omeprazole was reported.

Mean Residence Time (MRT): Warfarin

MRT of warfarin was reported.

Apparent Terminal Elimination Half-Life (t1/2): Caffeine

t1/2 of caffeine was reported.

Apparent Terminal Elimination Half-Life (t1/2): Paraxanthine

t1/2 of Paraxanthine was reported.

Apparent Terminal Elimination Half-Life (t1/2): Omeprazole

t1/2 of omeprazole was reported.

Apparent Terminal Elimination Half-Life (t1/2): Warfarin

t1/2 of warfarin was reported.

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes