Clinical trial NCT06181006: A Study to Evaluate Pirtobrutinib (LOXO-305) in Healthy Adult Participants
Official title: A Phase I, Single-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LOXO-305 in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
Collaborators: name: Loxo Oncology, Inc.
First posted: 2023-12-26
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of this study is to assess the safety and tolerability of pirtobrutinib and to look at the amount of the study drug, pirtobrutinib, that gets into the blood stream and how long it takes the body to get rid of it when given in healthy adult participants. For each participant, the total duration of the study will be 46 days, including screening.


Eligibility criteria: 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* Have previously completed or withdrawn from any other study investigating Pirtobrutinib (LOXO-305) and have previously received the investigational product

Primary outcomes:
measure: Number of Participants With One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs)
timeFrame: Baseline up to 46 days
Secondary outcomes:
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib
timeFrame: Day 1 (predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24 hours post-dose)
measure: PK: Area Under the Concentration Versus Time Curve From Hour Zero to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf) of Pirtobrutinib
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Percentage Extrapolation for AUC0-inf (%AUCextrap) of Pirtobrutinib
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Maximum Observed Plasma Concentration (Cmax) of Pirtobrutinib
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 1)
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 2)
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 3)
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib (Cohort 4)
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Apparent Volume of Distribution at Terminal Phase (Vz/F) of Pirtobrutinib
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
measure: PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib
timeFrame: Day 1 (Predose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 7, 9, 12, 24, 48, 72, 96, 120, 144, and 168 hours post-dose)
Other outcomes:
Locations:
city: Daytona Beach
country: United States
facility: Covance Clinical Research Unit
state: Florida
Study officials:
affiliation: Loxo Oncology, Inc.
name: Renee Ward, MD, PhD
role: STUDY_DIRECTOR
References: