A Drug Drug Interaction (DDI) Study of Pirtobrutinib (LOXO-305) and Different Formulations of Midazolam in Healthy Participants

Lilly

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Midazolam Syrup; Drug: Midazolam Solution; Drug: Pirtobrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT06180967

J2N-OX-JZND (Other Identifier)

LOXO-BTK-20008

Details and patient eligibility

About

The main purpose of this study is to assess the effect of Pirtobrutinib (LOXO-305) on how fast different formulations of midazolam gets into the blood stream and how long it takes the body to remove it when administered in healthy participants. The study will also access how much endogenous coproporphyrins I and III as biomarkers of OATP1B1 and OATP1B3 is in the bloodstream and how the body handles and eliminates them following single and multiple oral doses of Pirtobrutinib. Safety and tolerability of Pirtobrutinib will also be evaluated. For each participant, the total duration of the study will be 59 days, including screening.

Enrollment: 15 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/m²), 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 8-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
• Positive serologic test for hepatitis B surface antigen (HBsAg), hepatitis B virus immunoglobulin M (HBV IgM) core antibody, hepatitis C virus (HCV) antibody, or human immunodeficiency virus (HIV) antibody at Screening
• Positive polymerase chain reaction (PCR) test for COVID-19 at Screening or Check-in (Day -1)
• 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)
• Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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15 participants in 3 patient groups

Midazolam (Intravenous [IV] Bolus)

Experimental group

Description:

A single IV bolus dose of midazolam will be administered in the morning following a 10-hour fast prior to dosing and a 4-hour fast postdose on Day 1 and Day 15.

Treatment:

Drug: Midazolam Solution

Midazolam Oral

Experimental group

Description:

A single oral dose of midazolam will be administered in the morning following a 10-hour fast prior to dosing and a 4-hour fast postdose on Day 3 and Day 17.

Treatment:

Drug: Midazolam Syrup

Pirtobrutinib

Experimental group

Description:

Multiple oral doses of Pirtobrutinib once a day (QD) will be administered on Days 5 through Day 17.

Treatment:

Drug: Pirtobrutinib