Clinical trial NCT06215521: A Study to Evaluate the Effect of Pirtobrutinib (LOXO-305) on QTc Interval in Healthy Participants
Official title: A Phase I, Single-Dose, Randomized, Partially Double-Blind, Placebo- and Positive-Controlled, 3-Way Crossover Study to Evaluate the Effect of LOXO-305 on QTc Interval in Healthy 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: 2024-01-22
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The main purpose of this study is to assess the effect of Pirtobrutinib (LOXO-305) on the heart rate-corrected QT (QTc) interval and to conduct blood tests to measure how much pirtobrutinib (LOXO-305) is in the bloodstream and how the body handles and eliminates pirtobrutinib. The study will also evaluate the safety and tolerability of pirtobrutinib. The study will last up to 71 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 at Screening
* 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 15-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
* 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 received pirtobrutinib (LOXO-305) in any other study investigating pirtobrutinib (LOXO-305), within 30 days prior to Day 1

Primary outcomes:
measure: Placebo-corrected Change From Baseline in QT Interval Corrected Using Fridericia's Correction (QTcF) (ΔΔQTcF)
timeFrame: Baseline (Predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
Secondary outcomes:
measure: Change From Baseline in (Δ) QTcF
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Change From Baseline in Heart Rate (ΔHR)
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Change From Baseline in Pulse Rate (ΔPR)
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Change From Baseline in QRS Intervals (Δ QRS)
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Change From Baseline in Individualized Heart Rate-Corrected QT Interval (ΔQTcS), If a Substantial Heart Rate Effect Was Observed
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Change From Baseline in Optimized Heart Rate-Corrected QT Interval (ΔQTcI), If a Substantial Heart Rate Effect Was Observed
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR)
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR)
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Placebo-Corrected Change From Baseline in QRS (ΔΔQRS)
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Placebo-corrected Change From Baseline in ΔQTcF (ΔΔQTcF), If a Substantial Heart Rate Effect Was Observed
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Placebo-corrected Change From Baseline in Individualized Heart Rate-Corrected QT Interval (ΔΔQTcS), If a Substantial Heart Rate Effect Was Observed
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Placebo-corrected Change From Baseline in Optimized Heart Rate-Corrected QT Interval (ΔΔQTcI), If a Substantial Heart Rate Effect Was Observed
timeFrame: Baseline (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12 and 24 hours post-dose
measure: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Changes
timeFrame: Baseline up to Day 33
measure: Number of Participants With Treatment Emergent Changes in T-wave Morphology and U-wave Presence
timeFrame: Baseline up to Day 33
measure: Pharmacokinetic (PK): Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
measure: PK: Mean Residence Time (MRT) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
measure: PK: Apparent Volume of Distribution at the Terminal Phase (Vz/F) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
measure: PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
measure: PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
measure: PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
measure: PK: Area Under the Concentration-time Curve, From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24 hours post-dose
measure: PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
measure: PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
measure: PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
measure: PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib
timeFrame: Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8.5, 12, 24, 48, 72, and 96 hours post-dose
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance Clinical Research Unit 1341 Mockingbird Lane
state: Texas
city: Madison
country: United States
facility: Covance Clinical Research Unit 3402 Kinsman Blvd
state: Wisconsin
Study officials:
affiliation: Loxo Oncology, Inc.
name: Renee Ward, MD, PhD
role: STUDY_DIRECTOR
References: