A Safety, Tolerability, and Pharmacokinetic Study of Tucatinib in Healthy Japanese and Caucasian Subjects

A Phase 1, Open Label, Safety, Tolerability, and Pharmacokinetic Study of Tucatinib (ONT-380) in Healthy Japanese and Caucasian Subjects

This study is being done to compare the pharmacokinetics (PK) and safety/tolerability of tucatinib in healthy Japanese and Caucasian participants.

Three cohorts of healthy Japanese and Caucasian men and women will be admitted to the Clinical Research Unit (CRU) and receive multiple oral doses of tucatinib over 14 days with and without food.

Subjects will be in the study for up to 45 days, including the screening period.

Due to practical considerations, each cohort will be dosed sequentially (this is not a dose escalation study).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • PAREXEL International, Early Phase Clinical Unit - Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index between 18 and 32 kg/m^2 and a total body weight between 50 and 100 kg
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiograms, vital signs measurements, or clinical laboratory evaluations
• Female subjects participating in the study will be of non-childbearing potential. Male subjects will be surgically sterile for at least 90 days or will agree to use contraception during the study and for 90 days after last dose of study drug.

• Japanese subjects:

  1. Must have been born in Japan
  2. Must have 2 biological Japanese parents and 4 biological Japanese grandparents as confirmed by interview
  3. Must have spent less than 10 years outside of Japan, and has no significant changes in lifestyle, including diet, since leaving Japan

Exclusion Criteria:

• Significant history of metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder
• Current condition possibly affecting drug absorption
• History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
• History of stomach or intestinal surgery or resection that would potentially alter absorption or excretion of orally administered drugs
• History of alcoholism or drug/chemical abuse within 2 years of check-in
• History of regular alcohol consumption exceeding 7 drinks/week for female subjects or 14 drinks/week for male subjects
• Positive hepatitis panel and/or positive human immunodeficiency (HIV) test
• Liver function tests, serum creatinine, hemoglobin, or hematocrit values outside of the normal reference range
• Single 12-lead ECG demonstrating QTcF>450 msec for males or >470 msec for females
• Participation in a clinical study involving administration of an investigational drug in the past 30 days from last dose or 5 half-lives (whichever is longer)
• Use of any products known to alter drug absorption, metabolism or elimination processes, including St. John's wort and known strong inhibitors or inducers of CYP3A4 or CYP2C8, within 30 days
• Use of or intention to use any prescription or nonprescription products, including vitamins, minerals and herbal preparations within 14 days
• Use of tobacco- or nicotine-containing products within 3 months
• Receipt of blood products within 2 months
• Donation of blood from 56 days before the Screening Visit, plasma from 2 weeks before the Screening Visit or platelets from 6 weeks before the Screening Visit
• Poor peripheral venous access
• Have previously completed or withdrawn from this study or any other study investigating tucatinib and have previously received the study drug

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 50 mg twice daily on Days 1-13 and once daily on Day 14	Drug: Tucatinib; Administered via oral tablet
Experimental: Cohort 2; 150 mg twice daily on Days 1-13 and once daily on Day 14	Drug: Tucatinib; Administered via oral tablet
Experimental: Cohort 3; 300 mg twice daily on Days 1-13 and once daily on Day 14	Drug: Tucatinib; Administered via oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed concentration (Cmax) of tucatinib	14 days
Cmax of ONT-993	14 days
Time of the maximum observed concentration (tmax) of tucatinib	14 days
Tmax of ONT-993	14 days
AUC from time 0 to the time of last quantifiable concentration (AUClast) of tucatinib	14 days
AUClast of ONT-993	14 days
AUC from time 0 to 12 hours postdose (AUC0-12hr) of tucatinib	14 days
AUC0-12hr of ONT-993	14 days
AUC from time 0 extrapolated to infinity (AUC0-inf) of tucatinib	1 day
AUC from time 0 extrapolated to infinity (AUC0-inf) of ONT-993	1 day
Percentage of AUC0-inf due to extrapolation (%AUCextrap) of tucatinib	1 day
%AUCextrap of ONT-993	1 day
Apparent total clearance (CL/F) of tucatinib	14 days
Apparent volume of distribution during the terminal phase (Vz/F) of tucatinib	14 days
Metabolite-to-parent molar ratio based on AUC (MRAUC) of ONT-993	14 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of adverse events (AEs)	17 days

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Director: Joseph Woolery, PharmD, BCOP, Seagen Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 8, 2019
• Primary Completion (Actual): August 4, 2019
• Study Completion (Actual): August 4, 2019

Study Registration Dates

• First Submitted: April 10, 2019
• First Submitted That Met QC Criteria: April 11, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 6, 2019
• Last Update Submitted That Met QC Criteria: September 3, 2019
• Last Verified: September 1, 2019

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: SGNTUC-015

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