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Hepatic ImpairmentPhase 1NCT03722823

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

A Phase 1 study testing Tucatinib in people with Hepatic Impairment, run by Seagen Inc. at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for
Hepatic Impairment
What is being tested?
Tucatinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
4 sitesUnited States
Study dates
10 Oct 2018to 7 May 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • NOCCR Knoxville and Volunteer Research Group

    Knoxville, Tennessee, 37920

  • Orlando Clinical Research Center

    Orlando, Florida, 32809

  • Texas Liver Institute

    San Antonio, Texas, 78215

  • Orange County Research Center

    Tustin, California, 92780

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Tucatinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TucatinibDrug

    300mg oral single dose

Study groups in NCT03722823
Study groupRoleWhat they receive
Group 1: HealthyActive comparatorMatch-controlled healthy subjects with normal hepatic function
Receives: Drug: Tucatinib
Group 2: Mild Hepatic ImpairmentExperimentalSubjects with Mild hepatic impairment (Child-Pugh Class A, score of 5 or 6)
Receives: Drug: Tucatinib
Group 3: Moderate Hepatic ImpairmentExperimentalSubjects with Moderate hepatic impairment (Child-Pugh Class B, score of 7 to 9)
Receives: Drug: Tucatinib
Group 4: Severe Hepatic ImpairmentExperimentalSubjects with Severe hepatic impairment (Child-Pugh Class C, score of 10 to 14)
Receives: Drug: Tucatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Maximum observed concentration (Cmax)

    Pharmacokinetic (PK) endpoint of tucatinib

    Measured: Up to 48 hours

  2. Time of maximum observed concentration (Tmax)

    PK endpoint of tucatinib

    Measured: Up to 48 hours

  3. Area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC[0-t])

    PK endpoint of tucatinib

    Measured: Up to 48 hours

  4. AUC from time 0 to infinity (AUC[0-inf])

    PK endpoint of tucatinib

    Measured: Up to 48 hours

  5. Percentage extrapolation for AUC (%AUCextrap)

    PK endpoint of tucatinib

    Measured: 48 hours

  6. Apparent terminal elimination rate constant (λz)

    PK endpoint of tucatinib

    Measured: Up to 48 hours

  7. Apparent terminal elimination half-life (t½)

    PK endpoint of tucatinib

    Measured: Up to 48 hours

  8. Apparent total clearance

    PK endpoint of tucatinib

    Measured: Up to 48 hours

  9. Apparent volume of distribution during the terminal phase

    PK endpoint of tucatinib

    Measured: Up to 48 hours

  10. Mean residence time (MRT)

    PK endpoint of tucatinib

    Measured: Up to 48 hours

Secondary outcomes (9)

  1. Cmax

    PK endpoint of ONT-993

    Measured: Up to 48 hours

  2. Tmax

    PK endpoint of ONT-993

    Measured: Up to 48 hours

  3. AUC[0-t]

    PK endpoint of ONT-993

    Measured: Up to 48 hours

  4. (AUC[0-inf])

    PK endpoint of ONT-993

    Measured: Up to 48 hours

  5. %AUCextrap

    PK endpoint of ONT-993

    Measured: Up to 48 hours

  6. λz

    PK endpoint of ONT-993

    Measured: Up to 48 hours

  7. t½

    PK endpoint of ONT-993

    Measured: Up to 48 hours

  8. MRT

    PK endpoint of ONT-993

    Measured: Up to 48 hours

  9. Incidence of adverse events (AEs)

    As determined by assessment of AEs, clinical laboratory tests, physical examinations, vital signs measurements, and 12-lead ECG

    Measured: Up to 9 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Oct 2018
  2. Study start10 Oct 2018
  3. Primary completion7 May 2019
  4. Study completion7 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03722823
Sponsor's protocol ID
ONT-380-009
Status last verified
May 2019
First submitted
24 Oct 2018
Last updated
20 May 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 36471222

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Tucatinib in people with Hepatic Impairment, run by Seagen Inc. at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 May 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum observed concentration (Cmax) (time frame: Up to 48 hours). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03722823, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2019.

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