A Study to Evaluate the Effect of Pirtobrutinib (LOXO-305) on QTc Interval in Healthy Participants
- Registration Number
- NCT06215521
- Lead Sponsor
- Eli Lilly and Company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 31
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo (matched to Pirtobrutinib) a single oral dose on Day 1, 12 and 23 following a fast of at least 8 hours prior to and 6 hours after dosing. Pirtobrutinib Pirtobrutinib Pirtobrutinib a single oral dose on Day 1, 12 and 23 following a fast of at least 8 hours prior to and 6 hours after dosing. Moxifloxacin Moxifloxacin Moxifloxacin a single oral dose on Day 1, 12 and 23 following a fast of at least 8 hours prior to and 6 hours after dosing.
- Primary Outcome Measures
Name Time Method Cardiodynamics: Placebo-Corrected QT Interval Corrected Using Fridericia's Correction (QTcF) (ΔΔQTcF) 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Placebo-corrected ΔΔQTcF.
- Secondary Outcome Measures
Name Time Method Change From Baseline in (Δ)QTcF at Day 1, 12 and 23 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Change From Baseline in Heart Rate (ΔHR) at Day 1, 12 and 23 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Change-From-Baseline in Optimized Heart Rate-Corrected QT Interval (ΔQTcI) at Day 1, 12 and 23, If a Substantial Heart Rate Effect is Observed 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Change From Baseline in QRS intervals (Δ QRS) at Day 1, 12 and 23 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Placebo-Corrected Change From Baseline in Heart Rate (ΔΔHR) at Day 1, 12 and 23 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Placebo-Corrected ΔQTcF (ΔΔQTcF) at Day 1, 12 and 23, If a Substantial Heart Rate Effect is Observed 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Changes 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Number of participants who have increases(\>) in absolute treatment-emergent QTc (QTcF, and QTcS and QTcI) values \> 450 and ≤ 480 msec, \> 480 and ≤ 500 msec, or \> 500 msec, and changes from predose baseline of \> 30 and ≤ 60 msec, or \> 60 msec; increase in PR from predose baseline \> 25% to a PR\> 200 msec; increase in QRS from predose baseline \> 25% to a QRS \> 120 msec; decrease in HR from predose baseline \> 25% to a HR \< 50 bpm; and increase in HR from predose baseline \> 25% to a HR \> 100 bpm will be determined.
Percentage of AUC0-inf extrapolated (AUC%extrap) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Apparent Systemic Clearance (CL/F) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Mean Residence Time (MRT) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Apparent Volume of Distribution at the Terminal Phase (Vz/F) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Maximum Observed Concentration (Cmax) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Area Under the Concentration-time Curve, From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Change From Baseline in Pulse Rate (ΔPR) at Day 1, 12 and 23 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Change-From-Baseline in Individualized Heart Rate-Corrected QT interval (ΔQTcS) at Day 1, 12 and 23, If a Substantial Heart Rate Effect is Observed 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Placebo-Corrected Change From Baseline in Pulse Rate (ΔΔ PR) at Day 1, 12 and 23 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Placebo-Corrected Change From Baseline in QRS (ΔΔQRS) at Day 1, 12 and 23 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Placebo-Corrected Individualized Heart Rate-Corrected QT interval (ΔΔQTcS) at Day 1, 12 and 23, If a Substantial Heart Rate Effect is Observed 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Placebo-Corrected Optimized Heart Rate-Corrected QT Interval (ΔΔQTcI) at Day 1, 12 and 23, If a Substantial Heart Rate Effect is Observed 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 Treatment Emergent Changes in T-wave Morphology and U-Wave Presence at Day 1, 12 and 23 1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23 For T-wave morphology and U-wave presence treatment-emergent changes will be assessed.
Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Apparent Plasma Terminal Elimination Half-life (t½) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Area Under the Concentration-time Curve from Time 0 Extrapolated to Infinity (AUC0-inf) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23 Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib Pre dose and up to 96 hours post dose on Day 1, 12 and 23
Trial Locations
- Locations (2)
Covance Clinical Research Unit 1341 Mockingbird Lane
🇺🇸Dallas, Texas, United States
Covance Clinical Research Unit 3402 Kinsman Blvd
🇺🇸Madison, Wisconsin, United States