Effects of Tucatinib on Cardiac Repolarization in Healthy Participants

Sponsor

Seagen Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03777761

Collaborator

(none)

Enrollment

Location

Arms

3.1

Actual Duration (Months)

17.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: tucatinib Drug: placebo Drug: moxifloxacin	Phase 1

Detailed 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

The study will be double-blind in regard to tucatinib and placebo study treatments and open-label for the positive control, moxifloxacin.

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 6, 2018

Actual Primary Completion Date :

Mar 11, 2019

Actual Study Completion Date :

Mar 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Sequence ABC tucatinib + placebo + moxifloxacin (administered in sequential treatment periods)	Drug: tucatinib 300mg oral dose Drug: placebo Matching placebo for tucatinib Drug: moxifloxacin 400mg single oral dose
Experimental: Treatment Sequence CAB moxifloxacin + tucatinib + placebo (administered in sequential treatment periods)	Drug: tucatinib 300mg oral dose Drug: placebo Matching placebo for tucatinib Drug: moxifloxacin 400mg single oral dose
Experimental: Treatment Sequence BCA placebo + moxifloxacin + tucatinib (administered in sequential treatment periods)	Drug: tucatinib 300mg oral dose Drug: placebo Matching placebo for tucatinib Drug: moxifloxacin 400mg single oral dose
Experimental: Treatment Sequence CBA moxifloxacin + placebo + tucatinib (administered in sequential treatment periods)	Drug: tucatinib 300mg oral dose Drug: placebo Matching placebo for tucatinib Drug: moxifloxacin 400mg single oral dose
Experimental: Treatment Sequence ACB tucatinib + moxifloxacin + placebo (administered in sequential treatment periods)	Drug: tucatinib 300mg oral dose Drug: placebo Matching placebo for tucatinib Drug: moxifloxacin 400mg single oral dose
Experimental: Treatment Sequence BAC placebo + tucatinib + moxifloxacin (administered in sequential treatment periods)	Drug: tucatinib 300mg oral dose Drug: placebo Matching placebo for tucatinib Drug: moxifloxacin 400mg single oral dose

Outcome Measures

Primary Outcome Measures

Placebo-corrected change-from-baseline in QTcF [Up to 32 days]
QTcF is the QT interval corrected for heart rate using Fridericia's method.

Secondary Outcome Measures

Change from baseline in heart rate (HR) [Up to 32 days]
Change from baseline in QTcF [Up to 32 days]
Change from baseline in PR interval [Up to 32 days]
Change from baseline in QRS interval [Up to 32 days]
Placebo-corrected change from baseline in HR [Up to 32 days]
Placebo-corrected change from baseline in PR interval [Up to 32 days]
Placebo-corrected change from baseline in QRS interval [Up to 32 days]
• Number of participants who experience increases in absolute QTcF interval values >450 msec [Up to 32 days]
• Number of participants who experience QTcF interval changes from predose baseline of >30msec [Up to 32 days]
• Number of participants who experience an increase in PR interval from predose baseline of >25% to a PR >200 msec [Up to 32 days]
• Number of participants who experience an increase in QRS interval from predose baseline >25% to a QRS >120 msec [Up to 32 days]
• Number of participants who experience a decrease in heart rate >25% from baseline to a heart rate <50 [Up to 32 days]
• Number of participants who experience an increase in heart rate >25% from baseline to a heart rate >100 [Up to 32 days]
Frequency of treatment-emergent changes of T-wave morphology and U-wave presence [Up to 32 days]
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]
AUC from time 0 to the time of the last quantifiable concentration for tucatinib and ONT-993 [Up to 26 days]
Percentage of AUC[0-inf] due to extrapolation for tucatinib and ONT-993 [Up to 26 days]
Maximum observed concentration for tucatinib and ONT-993 [Up to 26 days]
Time of maximum observed concentration for tucatinib and ONT-993 [Up to 26 days]
Apparent terminal elimination half-life for tucatinib and ONT-993 [Up to 26 days]
Apparent total clearance for tucatinib [Up to 26 days]
Apparent volume of distribution during the terminal phase for tucatinib [Up to 26 days]
Metabolic ratio based on AUC for ONT-993 [Up to 26 days]
Incidence of adverse events (AEs) [Up to 32 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Clinical Research Unit - Dallas	Dallas	Texas	United States	75247

Sponsors and Collaborators

Seagen Inc.

Investigators

Study Director: Joseph Woolery, PharmD, BCOP, Seagen Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Seagen Inc.

ClinicalTrials.gov Identifier:

NCT03777761

Other Study ID Numbers:

ONT-380-011

First Posted:

Dec 17, 2018

Last Update Posted:

Apr 12, 2019

Last Verified:

Apr 1, 2019

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Moxifloxacin

Tucatinib

Study Results

No Results Posted as of Apr 12, 2019