Effects of Tucatinib on Cardiac Repolarization in Healthy Participants
- Registration Number
- NCT03777761
- Lead Sponsor
- Seagen Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 55
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence ABC placebo tucatinib + placebo + moxifloxacin (administered in sequential treatment periods) Treatment Sequence BAC placebo placebo + tucatinib + moxifloxacin (administered in sequential treatment periods) Treatment Sequence BCA placebo placebo + moxifloxacin + tucatinib (administered in sequential treatment periods) Treatment Sequence ACB placebo tucatinib + moxifloxacin + placebo (administered in sequential treatment periods) Treatment Sequence CAB placebo moxifloxacin + tucatinib + placebo (administered in sequential treatment periods) Treatment Sequence CBA placebo moxifloxacin + placebo + tucatinib (administered in sequential treatment periods) Treatment Sequence CAB tucatinib moxifloxacin + tucatinib + placebo (administered in sequential treatment periods) Treatment Sequence BAC tucatinib placebo + tucatinib + moxifloxacin (administered in sequential treatment periods) Treatment Sequence ABC tucatinib tucatinib + placebo + moxifloxacin (administered in sequential treatment periods) Treatment Sequence ABC moxifloxacin tucatinib + placebo + moxifloxacin (administered in sequential treatment periods) Treatment Sequence CAB moxifloxacin moxifloxacin + tucatinib + placebo (administered in sequential treatment periods) Treatment Sequence BCA tucatinib placebo + moxifloxacin + tucatinib (administered in sequential treatment periods) Treatment Sequence BCA moxifloxacin placebo + moxifloxacin + tucatinib (administered in sequential treatment periods) Treatment Sequence CBA tucatinib moxifloxacin + placebo + tucatinib (administered in sequential treatment periods) Treatment Sequence CBA moxifloxacin moxifloxacin + placebo + tucatinib (administered in sequential treatment periods) Treatment Sequence ACB tucatinib tucatinib + moxifloxacin + placebo (administered in sequential treatment periods) Treatment Sequence ACB moxifloxacin tucatinib + moxifloxacin + placebo (administered in sequential treatment periods) Treatment Sequence BAC moxifloxacin placebo + tucatinib + moxifloxacin (administered in sequential treatment periods)
- Primary Outcome Measures
Name Time Method 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
Name Time Method Apparent total clearance for tucatinib Up to 26 days Metabolic ratio based on AUC for ONT-993 Up to 26 days Percentage of AUC[0-inf] due to extrapolation for tucatinib and ONT-993 Up to 26 days Time of maximum observed concentration for tucatinib and ONT-993 Up to 26 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 Change from baseline in heart rate (HR) 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 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 • 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 AUC from time 0 to the time of the last quantifiable concentration for tucatinib and ONT-993 Up to 26 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 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 volume of distribution during the terminal phase for tucatinib Up to 26 days Incidence of adverse events (AEs) Up to 32 days
Trial Locations
- Locations (1)
Covance Clinical Research Unit - Dallas
🇺🇸Dallas, Texas, United States