Effects of Tucatinib on Cardiac Repolarization in Healthy Participants

Seagen

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: tucatinib; Drug: placebo; Drug: moxifloxacin

Study type: Interventional

Funder types: Industry

Identifiers

NCT03777761

ONT-380-011

Details and patient eligibility

About

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.

Full 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.

Enrollment: 55 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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55 participants in 6 patient groups

Treatment Sequence ABC

Experimental group

Description:

tucatinib + placebo + moxifloxacin (administered in sequential treatment periods)

Treatment:

Drug: tucatinib

Drug: placebo

Drug: moxifloxacin

Treatment Sequence CAB

Experimental group

Description:

moxifloxacin + tucatinib + placebo (administered in sequential treatment periods)

Treatment:

Drug: tucatinib

Drug: placebo

Drug: moxifloxacin

Treatment Sequence BCA

Experimental group

Description:

placebo + moxifloxacin + tucatinib (administered in sequential treatment periods)

Treatment:

Drug: tucatinib

Drug: placebo

Drug: moxifloxacin

Treatment Sequence CBA

Experimental group

Description:

moxifloxacin + placebo + tucatinib (administered in sequential treatment periods)

Treatment:

Drug: tucatinib

Drug: placebo

Drug: moxifloxacin

Treatment Sequence ACB

Experimental group

Description:

tucatinib + moxifloxacin + placebo (administered in sequential treatment periods)

Treatment:

Drug: tucatinib

Drug: placebo

Drug: moxifloxacin

Treatment Sequence BAC

Experimental group

Description:

placebo + tucatinib + moxifloxacin (administered in sequential treatment periods)

Treatment:

Drug: tucatinib

Drug: placebo

Drug: moxifloxacin