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The investigators are doing this study to find out if tucatinib is safe for patients with liver problems. This study will look at participants with mild, moderate, and severe liver problems. For each participant with liver problems who takes part, a matching healthy participant who is of similar age, similar body mass index (BMI), and of the same sex will also take part. The study will look at how the drug affects healthy participants compared to participants with liver problems.
This study is being conducted to provide information to develop dosing recommendations for tucatinib in subjects with hepatic impairment. The current study will be carried out in subjects with hepatic impairment according to 3 different Child-Pugh (CP) categories (Mild, Moderate, and Severe impairment), and in matched-control healthy subjects. The minimum number of matched-control healthy subjects will be enrolled in order to ensure that each hepatically-impaired subject has a healthy match. Each matched-control healthy subject will be enrolled following the enrollment of a Mild and/or Moderate and/or Severe hepatic impairment subject and will be matched by age (+/- 10 years), by BMI (+/- 20%), and by sex to the enrolled hepatic impairment subject(s). Each healthy subject may be matched with up to 1 subject within each hepatic impairment group. Based on these criteria, with 3 cohorts of 8 hepatically-impaired subjects enrolled in the study, the number of healthy control subjects required to be enrolled will be at least 8 and not more than 24.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: Healthy | Active Comparator | Match-controlled healthy subjects with normal hepatic function |
|
| Group 2: Mild Hepatic Impairment | Experimental | Subjects with Mild hepatic impairment (Child-Pugh Class A, score of 5 or 6) |
|
| Group 3: Moderate Hepatic Impairment | Experimental | Subjects with Moderate hepatic impairment (Child-Pugh Class B, score of 7 to 9) |
|
| Group 4: Severe Hepatic Impairment | Experimental | Subjects with Severe hepatic impairment (Child-Pugh Class C, score of 10 to 14) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tucatinib | Drug | 300mg oral single dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum observed concentration (Cmax) | Pharmacokinetic (PK) endpoint of tucatinib | Up to 48 hours |
| Time of maximum observed concentration (Tmax) | PK endpoint of tucatinib | Up to 48 hours |
| Area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC[0-t]) | PK endpoint of tucatinib | Up to 48 hours |
| AUC from time 0 to infinity (AUC[0-inf]) | PK endpoint of tucatinib | Up to 48 hours |
| Percentage extrapolation for AUC (%AUCextrap) | PK endpoint of tucatinib | 48 hours |
| Apparent terminal elimination rate constant (λz) | PK endpoint of tucatinib | Up to 48 hours |
| Apparent terminal elimination half-life (t½) | PK endpoint of tucatinib | Up to 48 hours |
| Apparent total clearance | PK endpoint of tucatinib | Up to 48 hours |
| Apparent volume of distribution during the terminal phase |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | PK endpoint of ONT-993 | Up to 48 hours |
| Tmax | PK endpoint of ONT-993 | Up to 48 hours |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joseph Woolery, PharmD, BCOP | Seagen Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Orange County Research Center | Tustin | California | 92780 | United States | ||
| Orlando Clinical Research Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36471222 | Derived | Topletz-Erickson AR, Lee AJ, Mayor JG, Sun H, Abdulrasool LI, Rustia EL, Walker LN, Endres CJ. The Pharmacokinetics and Safety of Tucatinib in Volunteers with Hepatic Impairment. Clin Pharmacokinet. 2022 Dec;61(12):1761-1770. doi: 10.1007/s40262-022-01183-6. Epub 2022 Dec 5. |
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| ID | Term |
|---|---|
| C000705452 | tucatinib |
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PK endpoint of tucatinib |
| Up to 48 hours |
| Mean residence time (MRT) | PK endpoint of tucatinib | Up to 48 hours |
| AUC[0-t] | PK endpoint of ONT-993 | Up to 48 hours |
| (AUC[0-inf]) | PK endpoint of ONT-993 | Up to 48 hours |
| %AUCextrap | PK endpoint of ONT-993 | Up to 48 hours |
| λz | PK endpoint of ONT-993 | Up to 48 hours |
| t½ | PK endpoint of ONT-993 | Up to 48 hours |
| MRT | PK endpoint of ONT-993 | Up to 48 hours |
| Incidence of adverse events (AEs) | As determined by assessment of AEs, clinical laboratory tests, physical examinations, vital signs measurements, and 12-lead ECG | Up to 9 days |
| Orlando |
| Florida |
| 32809 |
| United States |
| NOCCR Knoxville and Volunteer Research Group | Knoxville | Tennessee | 37920 | United States |
| Texas Liver Institute | San Antonio | Texas | 78215 | United States |