A Study of the Absorption, Metabolism, and Excretion of Tucatinib in Healthy Participants

Study Overview
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Brief Summary
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This study will look at how a drug (tucatinib) leaves the body and what happens to tucatinib while it is still in the body. Healthy participants will get one dose of tucatinib by mouth. Patients will be monitored for 8-14 days after they take the dose of tucatinib.

Detailed Description
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This study will examine the absorption, metabolism, and excretion of tucatinib in healthy individuals. Participants will receive one oral dose of tucatinib and will be followed for 8-14 days after the dose is received.

Official Title
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A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [¹⁴C]-Tucatinib Following a Single Oral Dose in Healthy Male and Female Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: tucatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, or lab evaluations Body mass index (BMI) between 18 and 32 kg/m² Weight between 50 and 100 kg Females must be of non-childbearing potential Males must agree to use contraception Exclusion Criteria: 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 History of alcoholism or drug/chemical abuse within 2 years Use of prescription products within 28 days prior to check in Use of tobacco- or nicotine-containing products within 3 months prior to check in

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tucatinib<br> | Drug: tucatinib<br>* Single dose of 300 mg of [¹⁴C]-tucatinib containing approximately 150 μCi of [¹⁴C] radioactivity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve (AUC) from time 0 to infinity (AUC[0-inf]) | PK outcome parameter for tucatinib, ONT-993, and total radioactivity derived from the whole blood and plasma concentration-time profiles | Up to 14 days | 
| AUC from time 0 to last quantifiable concentration | PK outcome parameter for tucatinib, ONT-993, and total radioactivity derived from the whole blood and plasma concentration-time profiles | Up to 14 days | 
| Maximum observed concentration | PK outcome parameter for tucatinib, ONT-993, and total radioactivity derived from the whole blood and plasma concentration-time profiles | Up to 14 days | 
| Time of maximum observed concentration | PK outcome parameter for tucatinib, ONT-993, and total radioactivity derived from the whole blood and plasma concentration-time profiles | Up to 14 days | 
| Apparent terminal elimination half-life | PK outcome parameter for tucatinib, ONT-993, and total radioactivity derived from the whole blood and plasma concentration-time profiles | Up to 14 days | 
| Apparent total clearance | PK outcome parameter for tucatinib derived from the whole blood and plasma concentration-time profiles | Up to 14 days | 
| Apparent volume of distribution | PK outcome parameter for tucatinib derived from the whole blood and plasma concentration-time profiles | Up to 14 days | 
| AUC[0-inf] plasma tucatinib/total radioactivity ratio | AUC[0-inf] of plasma tucatinib relative to AUC[0-inf] of plasma total radioactivity | Up to 14 days | 
| AUC[0-inf] blood/plasma ratio | AUC[0-inf] of whole blood total radioactivity to AUC[0-inf] of plasma total radioactivity | Up to 14 days | 
| Amount excreted in urine (Aeu) | PK outcome endpoint of tucatinib, ONT-993, and total radioactivity derived from urine collections | Up to 14 days | 
| Cumulative Aeu | PK outcome endpoint of tucatinib, ONT-993, and total radioactivity derived from urine collections | Up to 14 days | 
| Percentage excreted in urine (Feu) | PK outcome endpoint of tucatinib and total radioactivity derived from urine collections | Up to 14 days | 
| Cumulative Feu | PK outcome endpoint of tucatinib and total radioactivity derived from urine collections | Up 14 days | 
| Renal clearance | PK outcome endpoint of tucatinib derived from urine collections | Up to 14 days | 
| Amount excreted in feces [Aef] | PK outcome endpoint of total radioactivity derived from feces collection | Up to 14 days | 
| Cumulative Aef | PK outcome endpoint of total radioactivity derived from feces collection | Up to 14 days | 
| Percentage excreted in feces [Fef] | PK outcome endpoint of total radioactivity derived from feces collection | Up to 14 days | 
| Cumulative Fef | PK outcome endpoint of total radioactivity derived from feces collection | Up to 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative abundance of tucatinib and its metabolites eliminated in urine and feces |  | Up to 14 days | 
| Relative abundance of tucatinib and its metabolites in plasma |  | Up to 14 days | 
| Incidence of adverse events (AEs) |  | Up to 14 days |