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A Study to Evaluate the Effect of Pirtobrutinib (LOXO-305) on QTc Interval in Healthy Participants

Phase 1
Completed
Conditions
Healthy
Interventions
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
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
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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
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Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo (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.
PirtobrutinibPirtobrutinibPirtobrutinib 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.
MoxifloxacinMoxifloxacinMoxifloxacin 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
NameTimeMethod
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
NameTimeMethod
Change From Baseline in (Δ)QTcF at Day 1, 12 and 231.5 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 231.5 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 Observed1.5 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 231.5 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 231.5 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 Observed1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Changes1.5 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 PirtobrutinibPre dose and up to 96 hours post dose on Day 1, 12 and 23
Apparent Systemic Clearance (CL/F) of PirtobrutinibPre dose and up to 96 hours post dose on Day 1, 12 and 23
Mean Residence Time (MRT) of PirtobrutinibPre 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 PirtobrutinibPre dose and up to 96 hours post dose on Day 1, 12 and 23
Maximum Observed Concentration (Cmax) of PirtobrutinibPre 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 PirtobrutinibPre dose and up to 96 hours post dose on Day 1, 12 and 23
Apparent Terminal Elimination Rate Constant (λZ) of PirtobrutinibPre 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 231.5 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 Observed1.5 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 231.5 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 231.5 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 Observed1.5 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 Observed1.5 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 231.5 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 PirtobrutinibPre dose and up to 96 hours post dose on Day 1, 12 and 23
Apparent Plasma Terminal Elimination Half-life (t½) of PirtobrutinibPre 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 PirtobrutinibPre 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 PirtobrutinibPre 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

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