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

Lilly

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Omeprazole capsule; Drug: Caffeine Tablet; Drug: Warfarin tablet; Drug: Pirtobrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06215430

J2N-OX-JZNE (Other Identifier)

LOXO-BTK-20010

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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16 participants in 2 patient groups

Period 1: Probe Drug Cocktail

Experimental group

Description:

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.

Treatment:

Drug: Warfarin tablet

Drug: Caffeine Tablet

Drug: Omeprazole capsule

Period 2: Pirtobrutinib + Probe Drug Cocktail

Experimental group

Description:

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).

Treatment:

Drug: Pirtobrutinib

Drug: Warfarin tablet

Drug: Caffeine Tablet

Drug: Omeprazole capsule