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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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | 50 mg twice daily on Days 1-13 and once daily on Day 14 |
|
| Cohort 2 | Experimental | 150 mg twice daily on Days 1-13 and once daily on Day 14 |
|
| Cohort 3 | Experimental | 300 mg twice daily on Days 1-13 and once daily on Day 14 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tucatinib | Drug | Administered via oral tablet |
|
| Measure | Description | 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 | |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events (AEs) | 17 days |
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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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joseph Woolery, PharmD, BCOP | Seagen Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| PAREXEL International, Early Phase Clinical Unit - Los Angeles | Glendale | California | 91206 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39368039 | Derived | Zhang D, Taylor A, Zhao JJ, Endres CJ, Topletz-Erickson A. Population Pharmacokinetic Analysis of Tucatinib in Healthy Participants and Patients with Breast Cancer or Colorectal Cancer. Clin Pharmacokinet. 2024 Oct;63(10):1477-1487. doi: 10.1007/s40262-024-01412-0. Epub 2024 Oct 5. |
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| ID | Term |
|---|---|
| C000705452 | tucatinib |
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| %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 |