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

NCT06215521 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: LOXO-BTK-20011J2N-OX-JZNI
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Placebo-corrected Change From Baseline in QT Interval Corrected Using Fridericia's Correction (QTcF) (ΔΔQTcF)

  The cardiodynamic assessment was performed through 12-lead electrocardiogram (ECG) extracted from continuous recordings at pre-specified time points. Participants rested in supine position for at least 10 minutes prior to and 5 minutes after each time point for ECG extractions. The QT interval is the time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole. QT interval was corrected for heart rate using QTcF. Placebo-corrected change from baseline in QTcF (ΔΔQTcF) was calculated based on model-predicted effect.

  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 (25)

• Change From Baseline in (Δ) QTcF

  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

• Change From Baseline in Heart Rate (ΔHR)

  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

• Change From Baseline in Pulse Rate (ΔPR)

  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

• Change From Baseline in QRS Intervals (Δ QRS)

  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

• Change From Baseline in Individualized Heart Rate-Corrected QT Interval (ΔQTcS), If a Substantial Heart Rate Effect Was Observed

  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

Study Arms (3)

Pirtobrutinib

EXPERIMENTAL

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.

Drug: Pirtobrutinib

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Moxifloxacin

ACTIVE COMPARATOR

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.

Drug: Moxifloxacin

Interventions

Pirtobrutinib DRUG

Administered orally

Also known as: LOXO-305, LY3527727

Pirtobrutinib

Placebo DRUG

Administered orally

Placebo

Moxifloxacin DRUG

Administered orally

Moxifloxacin

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead
• Loxo Oncology, Inc.: collaborator

Study Sites (2)

Covance Clinical Research Unit 1341 Mockingbird Lane

Dallas, Texas, 75247, United States

Location

Covance Clinical Research Unit 3402 Kinsman Blvd

Madison, Wisconsin, 53704, United States

Location

MeSH Terms

Interventions

pirtobrutinib; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

08005455979

Study Officials

• Renee Ward, MD, PhD

  Loxo Oncology, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This is a partially double-blind study (for LOXO-305 only, not moxifloxacin).
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2023
• First Posted: January 22, 2024
• Study Start: December 15, 2020
• Primary Completion: March 31, 2021
• Study Completion: March 31, 2021
• Last Updated: February 24, 2025
• Results First Posted: February 24, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)