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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: tucatinib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • Covance Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Cascadian Therapeutics Inc.
• Investigators: Study Director: Alex Vo, PhD, Cascadian Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 30, 2017
• Primary Completion (Actual): January 30, 2018
• Study Completion (Actual): January 30, 2018

Study Registration Dates

• First Submitted: November 13, 2018
• First Submitted That Met QC Criteria: November 28, 2018
• First Posted (Actual): November 29, 2018

Study Record Updates

• Last Update Posted (Actual): November 29, 2018
• Last Update Submitted That Met QC Criteria: November 28, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tucatinib
• Other Study ID Numbers: ONT-380-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No