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

NCT ID: NCT03722823

Last Updated: 2019-05-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-10
• Study Completion Date: 2019-05-07

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.

Conditions

Hepatic Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1: Healthy

Match-controlled healthy subjects with normal hepatic function

Group Type: ACTIVE_COMPARATOR

Tucatinib

Intervention Type: DRUG

300mg oral single dose

Group 2: Mild Hepatic Impairment

Subjects with Mild hepatic impairment (Child-Pugh Class A, score of 5 or 6)

Group Type: EXPERIMENTAL

Tucatinib

Intervention Type: DRUG

300mg oral single dose

Group 3: Moderate Hepatic Impairment

Subjects with Moderate hepatic impairment (Child-Pugh Class B, score of 7 to 9)

Group Type: EXPERIMENTAL

Tucatinib

Intervention Type: DRUG

300mg oral single dose

Group 4: Severe Hepatic Impairment

Subjects with Severe hepatic impairment (Child-Pugh Class C, score of 10 to 14)

Group Type: EXPERIMENTAL

Tucatinib

Intervention Type: DRUG

300mg oral single dose

Interventions

Tucatinib

300mg oral single dose

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Seagen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Woolery, PharmD, BCOP

Role: STUDY_DIRECTOR

Seagen Inc.

Locations

Orange County Research Center

Tustin, California, United States

Orlando Clinical Research Center

Orlando, Florida, United States

NOCCR Knoxville and Volunteer Research Group

Knoxville, Tennessee, United States

Texas Liver Institute

San Antonio, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 36471222 (View on PubMed)

Other Identifiers

ONT-380-009

Identifier Type: -

Identifier Source: org_study_id