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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT06215521
• Other study ID #: LOXO-BTK-20011
• Secondary ID: J2N-OX-JZNI
• Status: Completed
• Phase: Phase 1
• Start date: December 15, 2020
• Est. completion date: March 31, 2021

Study information

• Verified date: January 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: March 31, 2021
• Est. primary completion date: March 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• Pirtobrutinib
Administered orally
• Placebo
Administered orally
• Moxifloxacin
Administered orally

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit 1341 Mockingbird Lane	Dallas	Texas
United States	Covance Clinical Research Unit 3402 Kinsman Blvd	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Eli Lilly and Company	Loxo Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cardiodynamics: Placebo-Corrected QT Interval Corrected Using Fridericia's Correction (QTcF) (??QTcF)	Placebo-corrected ??QTcF.	1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Change From Baseline in (?)QTcF at Day 1, 12 and 23		1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Change From Baseline in Heart Rate (?HR) at Day 1, 12 and 23		1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Change From Baseline in Pulse Rate (?PR) at Day 1, 12 and 23		1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Change From Baseline in QRS intervals (? QRS) at Day 1, 12 and 23		1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Change-From-Baseline in Individualized Heart Rate-Corrected QT interval (?QTcS) 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
Secondary	Change-From-Baseline in Optimized Heart Rate-Corrected QT Interval (?QTcI) 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
Secondary	Placebo-Corrected Change From Baseline in Heart Rate (??HR) at Day 1, 12 and 23		1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Placebo-Corrected Change From Baseline in Pulse Rate (?? PR) at Day 1, 12 and 23		1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Placebo-Corrected Change From Baseline in QRS (??QRS) at Day 1, 12 and 23		1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Placebo-Corrected ?QTcF (??QTcF) 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
Secondary	Placebo-Corrected Individualized Heart Rate-Corrected QT interval (??QTcS) 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
Secondary	Placebo-Corrected Optimized Heart Rate-Corrected QT Interval (??QTcI) 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
Secondary	Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Changes	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.	1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Treatment Emergent Changes in T-wave Morphology and U-Wave Presence at Day 1, 12 and 23	For T-wave morphology and U-wave presence treatment-emergent changes will be assessed.	1.5 hours pre dose through 24 hours post dose on Day 1, 12 and 23
Secondary	Percentage of AUC0-inf extrapolated (AUC%extrap) of Pirtobrutinib		Pre dose and up to 96 hours post dose on Day 1, 12 and 23
Secondary	Mean Residence Time (MRT) of Pirtobrutinib		Pre dose and up to 96 hours post dose on Day 1, 12 and 23
Secondary	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
Secondary	Time to Maximum Observed Plasma Concentration (Tmax) of Pirtobrutinib		Pre dose and up to 96 hours post dose on Day 1, 12 and 23
Secondary	Apparent Plasma Terminal Elimination Half-life (t½) of Pirtobrutinib		Pre dose and up to 96 hours post dose on Day 1, 12 and 23
Secondary	Maximum Observed Concentration (Cmax) of Pirtobrutinib		Pre dose and up to 96 hours post dose on Day 1, 12 and 23
Secondary	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
Secondary	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
Secondary	Apparent Systemic Clearance (CL/F) of Pirtobrutinib		Pre dose and up to 96 hours post dose on Day 1, 12 and 23
Secondary	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
Secondary	Apparent Terminal Elimination Rate Constant (?Z) of Pirtobrutinib		Pre dose and up to 96 hours post dose on Day 1, 12 and 23