A Safety Study of Tucatinib in Healthy and Hepatically-Impaired Subjects

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03722823
• Other study ID #: ONT-380-009
• Status: Completed
• Phase: Phase 1
• Start date: October 10, 2018
• Est. completion date: May 7, 2019

Study information

• Verified date: May 2019
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 37
• Est. completion date: May 7, 2019
• Est. primary completion date: May 7, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatic Impairment

Intervention

Drug:
• Tucatinib
300mg oral single dose

Locations

Country	Name	City	State
United States	NOCCR Knoxville and Volunteer Research Group	Knoxville	Tennessee
United States	Orlando Clinical Research Center	Orlando	Florida
United States	Texas Liver Institute	San Antonio	Texas
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum observed concentration (Cmax)	Pharmacokinetic (PK) endpoint of tucatinib	Up to 48 hours
Primary	Time of maximum observed concentration (Tmax)	PK endpoint of tucatinib	Up to 48 hours
Primary	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
Primary	AUC from time 0 to infinity (AUC[0-inf])	PK endpoint of tucatinib	Up to 48 hours
Primary	Percentage extrapolation for AUC (%AUCextrap)	PK endpoint of tucatinib	48 hours
Primary	Apparent terminal elimination rate constant (?z)	PK endpoint of tucatinib	Up to 48 hours
Primary	Apparent terminal elimination half-life (t½)	PK endpoint of tucatinib	Up to 48 hours
Primary	Apparent total clearance	PK endpoint of tucatinib	Up to 48 hours
Primary	Apparent volume of distribution during the terminal phase	PK endpoint of tucatinib	Up to 48 hours
Primary	Mean residence time (MRT)	PK endpoint of tucatinib	Up to 48 hours
Secondary	Cmax	PK endpoint of ONT-993	Up to 48 hours
Secondary	Tmax	PK endpoint of ONT-993	Up to 48 hours
Secondary	AUC[0-t]	PK endpoint of ONT-993	Up to 48 hours
Secondary	(AUC[0-inf])	PK endpoint of ONT-993	Up to 48 hours
Secondary	%AUCextrap	PK endpoint of ONT-993	Up to 48 hours
Secondary	?z	PK endpoint of ONT-993	Up to 48 hours
Secondary	t½	PK endpoint of ONT-993	Up to 48 hours
Secondary	MRT	PK endpoint of ONT-993	Up to 48 hours
Secondary	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