Phase 1
Completed N=31
A Study to Evaluate the Effect of Pirtobrutinib (LOXO-305) on QTc Interval in Healthy Participants
Healthy
Source: ClinicalTrials.gov NCT06215521 ↗
Enrolled (actual)
31
Serious AEs
0.0%
Results posted
Feb 2025
Primary outcomePrimary: Placebo-corrected Change From Baseline in QT Interval Corrected Using Fridericia's Correction (QTcF) (ΔΔQTcF) — 0.73 milliseconds (msec)
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Placebo-corrected Change From Baseline in QT Interval Corrected Using Fridericia's Correction (QTcF) (ΔΔQTcF) |
0.73 | — |
| SECONDARY Change From Baseline in (Δ) QTcF |
-0.4; 0.0; -0.1; -4.5; -2.8; 4.2 | — |
| SECONDARY Change From Baseline in Heart Rate (ΔHR) |
0.1; -0.9; -0.5; -1.2; 0.0; -0.4 | — |
| SECONDARY Change From Baseline in Pulse Rate (ΔPR) |
-2.6; -0.8; 0.3; 1.5; 0.3; 1.0 | — |
| SECONDARY Change From Baseline in QRS Intervals (Δ QRS) |
0.0; 0.0; 0.2; -0.1; 0.2; 0.0 | — |
| SECONDARY Change From Baseline in Individualized Heart Rate-Corrected QT Interval (ΔQTcS), If a Substantial Heart Rate Effect Was Observed |
NA; NA | — |
| SECONDARY Change From Baseline in Optimized Heart Rate-Corrected QT Interval (ΔQTcI), If a Substantial Heart Rate Effect Was Observed |
NA; NA | — |
| SECONDARY Placebo-corrected Change From Baseline in Heart Rate (ΔΔHR) |
0.9; 0.1; 0.6; 3.0; 0.4; 3.8 | — |
| SECONDARY Placebo-corrected Change From Baseline in Pulse Rate (ΔΔ PR) |
-1.9; -1.2; -1.2; -2.1; -0.7; -2.5 | — |
| SECONDARY Placebo-Corrected Change From Baseline in QRS (ΔΔQRS) |
0.0; -0.3; 0.3; 0.1; 0.2; 0.3 | — |
| SECONDARY Placebo-corrected Change From Baseline in ΔQTcF (ΔΔQTcF), If a Substantial Heart Rate Effect Was Observed |
NA; NA | — |
| SECONDARY Placebo-corrected Change From Baseline in Individualized Heart Rate-Corrected QT Interval (ΔΔQTcS), If a Substantial Heart Rate Effect Was Observed |
NA; NA | — |
| SECONDARY Placebo-corrected Change From Baseline in Optimized Heart Rate-Corrected QT Interval (ΔΔQTcI), If a Substantial Heart Rate Effect Was Observed |
NA; NA | — |
| SECONDARY Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Changes |
0; 0 | — |
| SECONDARY Number of Participants With Treatment Emergent Changes in T-wave Morphology and U-wave Presence |
0; 0; 0; 0 | — |
| SECONDARY Pharmacokinetic (PK): Percentage of AUC0-inf Extrapolated (AUC%Extrap) of Pirtobrutinib |
5.41 | — |
| SECONDARY PK: Mean Residence Time (MRT) of Pirtobrutinib |
33.6 | — |
| SECONDARY PK: Apparent Volume of Distribution at the Terminal Phase (Vz/F) of Pirtobrutinib |
62.1 | — |
| SECONDARY PK: Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib |
4.01 | — |
| SECONDARY PK: Apparent Plasma Terminal Elimination Half-life (t1/2) of Pirtobrutinib |
23.0 | — |
| SECONDARY PK: Maximum Observed Concentration (Cmax) of Pirtobrutinib |
14300 | — |
| SECONDARY PK: Area Under the Concentration-time Curve, From Time 0 to 24 Hours Post-dose (AUC0-24) of Pirtobrutinib |
229000 | — |
| SECONDARY PK: Area Under the Concentration-time Curve, From Time 0 to the Last Measurable Concentration (AUC0-t) of Pirtobrutinib |
452000 | — |
| SECONDARY PK: Apparent Systemic Clearance (CL/F) of Pirtobrutinib |
1.88 | — |
| SECONDARY PK: Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf) of Pirtobrutinib |
480000 | — |
| SECONDARY PK: Apparent Terminal Elimination Rate Constant (λZ) of Pirtobrutinib |
0.0320; 0.0270; 0.0356; 0.0259; 0.0270; 0.0330 | — |
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
Data sourced from ClinicalTrials.gov (NCT06215521). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.