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

May 16, 2019 updated by: Seagen Inc.

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
37

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Tustin, California, United States, 92780
        • Orange County Research Center
    • Florida
      • Orlando, Florida, United States, 32809
        • Orlando Clinical Research Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • NOCCR Knoxville and Volunteer Research Group
    • Texas
      • San Antonio, Texas, United States, 78215
        • Texas Liver Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Group 1: Healthy
Match-controlled healthy subjects with normal hepatic function
Drug: Tucatinib
300mg oral single dose
Experimental: Group 2: Mild Hepatic Impairment
Subjects with Mild hepatic impairment (Child-Pugh Class A, score of 5 or 6)
Drug: Tucatinib
300mg oral single dose
Experimental: Group 3: Moderate Hepatic Impairment
Subjects with Moderate hepatic impairment (Child-Pugh Class B, score of 7 to 9)
Drug: Tucatinib
300mg oral single dose
Experimental: Group 4: Severe Hepatic Impairment
Subjects with Severe hepatic impairment (Child-Pugh Class C, score of 10 to 14)
Drug: Tucatinib
300mg oral single dose

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum observed concentration (Cmax)
Time Frame: Up to 48 hours
Pharmacokinetic (PK) endpoint of tucatinib
Up to 48 hours
Time of maximum observed concentration (Tmax)
Time Frame: Up to 48 hours
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])
Time Frame: Up to 48 hours
PK endpoint of tucatinib
Up to 48 hours
AUC from time 0 to infinity (AUC[0-inf])
Time Frame: Up to 48 hours
PK endpoint of tucatinib
Up to 48 hours
Percentage extrapolation for AUC (%AUCextrap)
Time Frame: 48 hours
PK endpoint of tucatinib
48 hours
Apparent terminal elimination rate constant (λz)
Time Frame: Up to 48 hours
PK endpoint of tucatinib
Up to 48 hours
Apparent terminal elimination half-life (t½)
Time Frame: Up to 48 hours
PK endpoint of tucatinib
Up to 48 hours
Apparent total clearance
Time Frame: Up to 48 hours
PK endpoint of tucatinib
Up to 48 hours
Apparent volume of distribution during the terminal phase
Time Frame: Up to 48 hours
PK endpoint of tucatinib
Up to 48 hours
Mean residence time (MRT)
Time Frame: Up to 48 hours
PK endpoint of tucatinib
Up to 48 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Cmax
Time Frame: Up to 48 hours
PK endpoint of ONT-993
Up to 48 hours
Tmax
Time Frame: Up to 48 hours
PK endpoint of ONT-993
Up to 48 hours
AUC[0-t]
Time Frame: Up to 48 hours
PK endpoint of ONT-993
Up to 48 hours
(AUC[0-inf])
Time Frame: Up to 48 hours
PK endpoint of ONT-993
Up to 48 hours
%AUCextrap
Time Frame: Up to 48 hours
PK endpoint of ONT-993
Up to 48 hours
λz
Time Frame: Up to 48 hours
PK endpoint of ONT-993
Up to 48 hours
t½
Time Frame: Up to 48 hours
PK endpoint of ONT-993
Up to 48 hours
MRT
Time Frame: Up to 48 hours
PK endpoint of ONT-993
Up to 48 hours
Incidence of adverse events (AEs)
Time Frame: Up to 9 days
As determined by assessment of AEs, clinical laboratory tests, physical examinations, vital signs measurements, and 12-lead ECG
Up to 9 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Seagen Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Joseph Woolery, PharmD, BCOP, Seagen Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 10, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 7, 2019

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 7, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 24, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 29, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 20, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 16, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ONT-380-009

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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