Clinical trial NCT03777761: Effects of Tucatinib on Cardiac Repolarization in Healthy Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2018-12-17
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Placebo-corrected change-from-baseline in QTcF
timeFrame: Up to 32 days
Secondary outcomes:
measure: Change from baseline in heart rate (HR)
timeFrame: Up to 32 days
measure: Change from baseline in QTcF
timeFrame: Up to 32 days
measure: Change from baseline in PR interval
timeFrame: Up to 32 days
measure: Change from baseline in QRS interval
timeFrame: Up to 32 days
measure: Placebo-corrected change from baseline in HR
timeFrame: Up to 32 days
measure: Placebo-corrected change from baseline in PR interval
timeFrame: Up to 32 days
measure: Placebo-corrected change from baseline in QRS interval
timeFrame: Up to 32 days
measure: • Number of participants who experience increases in absolute QTcF interval values >450 msec
timeFrame: Up to 32 days
measure: • Number of participants who experience QTcF interval changes from predose baseline of >30msec
timeFrame: Up to 32 days
measure: • Number of participants who experience an increase in PR interval from predose baseline of >25% to a PR >200 msec
timeFrame: Up to 32 days
measure: • Number of participants who experience an increase in QRS interval from predose baseline >25% to a QRS >120 msec
timeFrame: Up to 32 days
measure: • Number of participants who experience a decrease in heart rate >25% from baseline to a heart rate <50
timeFrame: Up to 32 days
measure: • Number of participants who experience an increase in heart rate >25% from baseline to a heart rate >100
timeFrame: Up to 32 days
measure: Frequency of treatment-emergent changes of T-wave morphology and U-wave presence
timeFrame: Up to 32 days
measure: Area under the concentration-time curve (AUC) from time 0 extrapolated to infinity (AUC[0-inf]) for tucatinib and ONT-993
timeFrame: Up to 26 days
measure: AUC from time 0 to the time of the last quantifiable concentration for tucatinib and ONT-993
timeFrame: Up to 26 days
measure: Percentage of AUC[0-inf] due to extrapolation for tucatinib and ONT-993
timeFrame: Up to 26 days
measure: Maximum observed concentration for tucatinib and ONT-993
timeFrame: Up to 26 days
measure: Time of maximum observed concentration for tucatinib and ONT-993
timeFrame: Up to 26 days
measure: Apparent terminal elimination half-life for tucatinib and ONT-993
timeFrame: Up to 26 days
measure: Apparent total clearance for tucatinib
timeFrame: Up to 26 days
measure: Apparent volume of distribution during the terminal phase for tucatinib
timeFrame: Up to 26 days
measure: Metabolic ratio based on AUC for ONT-993
timeFrame: Up to 26 days
measure: Incidence of adverse events (AEs)
timeFrame: Up to 32 days
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Covance Clinical Research Unit - Dallas
state: Texas
Study officials:
affiliation: Seagen Inc.
name: Joseph Woolery, PharmD, BCOP
role: STUDY_DIRECTOR
References: