Clinical trial NCT03914755: A Safety, Tolerability, and Pharmacokinetic Study of Tucatinib in Healthy Japanese and Caucasian Subjects
Official title: A Phase 1, Open Label, Safety, Tolerability, and Pharmacokinetic Study of Tucatinib (ONT-380) in Healthy Japanese and Caucasian Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2019-04-16
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Maximum observed concentration (Cmax) of tucatinib
timeFrame: 14 days
measure: Cmax of ONT-993
timeFrame: 14 days
measure: Time of the maximum observed concentration (tmax) of tucatinib
timeFrame: 14 days
measure: Tmax of ONT-993
timeFrame: 14 days
measure: AUC from time 0 to the time of last quantifiable concentration (AUClast) of tucatinib
timeFrame: 14 days
measure: AUClast of ONT-993
timeFrame: 14 days
measure: AUC from time 0 to 12 hours postdose (AUC0-12hr) of tucatinib
timeFrame: 14 days
measure: AUC0-12hr of ONT-993
timeFrame: 14 days
measure: AUC from time 0 extrapolated to infinity (AUC0-inf) of tucatinib
timeFrame: 1 day
measure: AUC from time 0 extrapolated to infinity (AUC0-inf) of ONT-993
timeFrame: 1 day
measure: Percentage of AUC0-inf due to extrapolation (%AUCextrap) of tucatinib
timeFrame: 1 day
measure: %AUCextrap of ONT-993
timeFrame: 1 day
measure: Apparent total clearance (CL/F) of tucatinib
timeFrame: 14 days
measure: Apparent volume of distribution during the terminal phase (Vz/F) of tucatinib
timeFrame: 14 days
measure: Metabolite-to-parent molar ratio based on AUC (MRAUC) of ONT-993
timeFrame: 14 days
Secondary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: 17 days
Other outcomes:
Locations:
city: Glendale
country: United States
facility: PAREXEL International, Early Phase Clinical Unit - Los Angeles
state: California
Study officials:
affiliation: Seagen Inc.
name: Joseph Woolery, PharmD, BCOP
role: STUDY_DIRECTOR
References: