Effects of Tucatinib on Cardiac Repolarization in Healthy Participants

Healthy Clinical Trial

Official title:

A Phase 1, Randomized, Partially Double-Blind, Placebo- and Positive-controlled Study to Evaluate the Effect of Tucatinib on Cardiac Repolarization in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03777761
• Other study ID #: ONT-380-011
• Status: Completed
• Phase: Phase 1
• Start date: December 6, 2018
• Est. completion date: March 11, 2019

Study information

• Verified date: April 2019
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is looking at how the study drug, tucatinib, affects the heart. Tucatinib is being studied as a possible treatment for breast cancer. This study will recruit healthy volunteers. There are 3 parts in the study. Each volunteer will be in all 3 parts. One part will be to take the study drug, the second part will be to take a placebo (pill with no medicine), and the third part will be to take moxifloxacin. The volunteers will only know what part of the study they are in when they take moxifloxacin. For the study drug and placebo parts, volunteers will take 2 pills by mouth for 5 days. For the moxifloxacin part, volunteers will take 1 pill by mouth for 1 day.

Description:

This study will evaluate the effects of a steady state therapeutic dose of tucatinib on QTcF (QT interval corrected for heart rate using Fridericia's method) in healthy individuals. In this design, study treatment will be dosed in 3 sequential treatment periods:

Treatment A: Oral doses of 300mg tucatinib for 5 days

Treatment B: Oral doses of matching placebo for tucatinib for 5 days

Treatment C: A single oral dose of 400 mg of moxifloxacin

Patients will be randomized based on 2-Williams-square design to 1 of 6 treatment sequences to maintain the study blind for tucatinib and placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: March 11, 2019
• Est. primary completion date: March 11, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Good health, determined by medical history, physical examination, 12-lead ECG, vital signs measurements, or clinical laboratory evaluations

• Body mass index (BMI) between 18 and 32 kg/m^2

• Body weight between 50 and 100 kg

• Female subjects must be of non-childbearing potential

• Male subjects must agree to use contraception or be surgically sterile for at least 90 days

Exclusion Criteria:

• Significant history of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder

• Any condition affecting drug absorption

• History of hypersensitivity or allergy to any drug compound, food, or other substance

• Single 12-lead ECG demonstrating QTcF >450 msec for males or >470 msec for females, or history/evidence of long QT syndrome

• History of alcoholism or drug/chemical abuse within 2 years

• Use of prescription products within 30 days prior to check in

• Use of nonprescription products within 14 days prior to check in, including vitamins, minerals, and herbal supplements

• Use of tobacco- or nicotine-containing products within 3 months prior to check in

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• tucatinib
300mg oral dose
• placebo
Matching placebo for tucatinib
• moxifloxacin
400mg single oral dose

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit - Dallas	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Placebo-corrected change-from-baseline in QTcF	QTcF is the QT interval corrected for heart rate using Fridericia's method.	Up to 32 days
Secondary	Change from baseline in heart rate (HR)		Up to 32 days
Secondary	Change from baseline in QTcF		Up to 32 days
Secondary	Change from baseline in PR interval		Up to 32 days
Secondary	Change from baseline in QRS interval		Up to 32 days
Secondary	Placebo-corrected change from baseline in HR		Up to 32 days
Secondary	Placebo-corrected change from baseline in PR interval		Up to 32 days
Secondary	Placebo-corrected change from baseline in QRS interval		Up to 32 days
Secondary	• Number of participants who experience increases in absolute QTcF interval values >450 msec		Up to 32 days
Secondary	• Number of participants who experience QTcF interval changes from predose baseline of >30msec		Up to 32 days
Secondary	• Number of participants who experience an increase in PR interval from predose baseline of >25% to a PR >200 msec		Up to 32 days
Secondary	• Number of participants who experience an increase in QRS interval from predose baseline >25% to a QRS >120 msec		Up to 32 days
Secondary	• Number of participants who experience a decrease in heart rate >25% from baseline to a heart rate <50		Up to 32 days
Secondary	• Number of participants who experience an increase in heart rate >25% from baseline to a heart rate >100		Up to 32 days
Secondary	Frequency of treatment-emergent changes of T-wave morphology and U-wave presence		Up to 32 days
Secondary	Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUC[0-inf]) for tucatinib and ONT-993		Up to 26 days
Secondary	AUC from time 0 to the time of the last quantifiable concentration for tucatinib and ONT-993		Up to 26 days
Secondary	Percentage of AUC[0-inf] due to extrapolation for tucatinib and ONT-993		Up to 26 days
Secondary	Maximum observed concentration for tucatinib and ONT-993		Up to 26 days
Secondary	Time of maximum observed concentration for tucatinib and ONT-993		Up to 26 days
Secondary	Apparent terminal elimination half-life for tucatinib and ONT-993		Up to 26 days
Secondary	Apparent total clearance for tucatinib		Up to 26 days
Secondary	Apparent volume of distribution during the terminal phase for tucatinib		Up to 26 days
Secondary	Metabolic ratio based on AUC for ONT-993		Up to 26 days
Secondary	Incidence of adverse events (AEs)		Up to 32 days