Clinical trial NCT03722823: A Safety Study of Tucatinib in Healthy and Hepatically-Impaired Subjects
Official title: An Open-label, Non-randomized, Single-dose, Parallel-group, Safety, Tolerability, and Pharmacokinetic Study of Tucatinib Administered at 300 mg in Fasted, Hepatically-impaired Male and Female Subjects and Fasted Matched-control Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2018-10-29
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* In good general health, except for additional inclusion criteria related to subjects with hepatic impairment
* Within body mass index (BMI) range of 18 to 37 kg/m\^2 (inclusive)
* Males capable of fathering a child must agree to use contraception from check in through 90 days after dose administration
* Females must be of nonchildbearing potential
* Able to understand and provide written informed consent
* Able to comply with all study procedures, including the 3-night stay at the clinical site and follow-up phone call
* Healthy subjects only: matched to subjects with Mild and/or Moderate and/or Severe hepatic impairment in sex, age (+/- 10 years), and BMI (+/- 20%).
* Hepatic impairment subjects only: considered to have Mild, Moderate, or Severe hepatic impairment that has been clinically stable for at least 1 month
* Hepatic impairment patients only: currently on stable medication regimen

Exclusion Criteria:

* Subjects with at-rest vital signs outside of the following ranges: heart rate (40 to 120 bpm), systolic blood pressure (90 to 150 mmHg), diastolic blood pressure (40 to 95 mmHg)
* Clinically significant abnormal laboratory values or physical examination findings
* Evidence/history of long QT syndrome
* Use of drugs/substances known to be inhibitors or inducers of CYP3A4 or CYP2C8 enzyme within 30 days
* Consumption of foods or beverages containing poppy seeds, grapefruit, or Seville oranges within 7 days of check-in
* Consumption of alcohol-, citric acid-, caffeine-, or xanthine-containing foods or beverages within 48 hours prior to check in
* Subjects with known alcohol and/or drug abuse within 1 month prior to check in
* History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
* History of congenital nonhemolytic hyperbilirubinemia
* History of stomach or intestinal surgery that would potentially alter absorption and/or excretion of orally administered drugs
* Prior doses of tucatinib
* Prior dose of any investigational drug within the past 30 days or 5 half-lives

Primary outcomes:
measure: Maximum observed concentration (Cmax)
timeFrame: Up to 48 hours
measure: Time of maximum observed concentration (Tmax)
timeFrame: Up to 48 hours
measure: Area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC[0-t])
timeFrame: Up to 48 hours
measure: AUC from time 0 to infinity (AUC[0-inf])
timeFrame: Up to 48 hours
measure: Percentage extrapolation for AUC (%AUCextrap)
timeFrame: 48 hours
measure: Apparent terminal elimination rate constant (λz)
timeFrame: Up to 48 hours
measure: Apparent terminal elimination half-life (t½)
timeFrame: Up to 48 hours
measure: Apparent total clearance
timeFrame: Up to 48 hours
measure: Apparent volume of distribution during the terminal phase
timeFrame: Up to 48 hours
measure: Mean residence time (MRT)
timeFrame: Up to 48 hours
Secondary outcomes:
measure: Cmax
timeFrame: Up to 48 hours
measure: Tmax
timeFrame: Up to 48 hours
measure: AUC[0-t]
timeFrame: Up to 48 hours
measure: (AUC[0-inf])
timeFrame: Up to 48 hours
measure: %AUCextrap
timeFrame: Up to 48 hours
measure: λz
timeFrame: Up to 48 hours
measure: t½
timeFrame: Up to 48 hours
measure: MRT
timeFrame: Up to 48 hours
measure: Incidence of adverse events (AEs)
timeFrame: Up to 9 days
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Knoxville
country: United States
facility: NOCCR Knoxville and Volunteer Research Group
state: Tennessee
city: San Antonio
country: United States
facility: Texas Liver Institute
state: Texas
Study officials:
affiliation: Seagen Inc.
name: Joseph Woolery, PharmD, BCOP
role: STUDY_DIRECTOR
References: