Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment

December 6, 2020 updated by: Novartis Pharmaceuticals

A Phase I, Open Label, Multicenter, Single Dose Study to Evaluate the Pharmacokinetics of Dabrafenib in Healthy Subjects With Normal Hepatic Function and Subjects With Impaired Hepatic Function

To characterize the pharmacokinetics and safety of dabrafenib following a single 100 mg oral dose in subjects with moderate and severe hepatic impairment.

Study Overview

Status

Status

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

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.

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.
5

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
      • Los Angeles, California, United States, 900017
        • American Institute of Research
    • Florida
      • DeBary, Florida, United States, 32713
        • Omega Research Consultants LLC
    • New Jersey
      • Berlin, New Jersey, United States, 08009
        • Hassman Research Institute
    • North Carolina
      • Raleigh, North Carolina, United States, 27612
        • Wake Research Associates Oncology

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 (for all subjects)

  • Male and/or female subjects 18-75 years of age
  • Females must be of non-childbearing potential . All non-postmenopausal females must have a confirmed negative serum pregnancy
  • Subjects in good health condition as determined by no clinically significant findings from medical history and physical examination.
  • Body mass index (BMI) between ≥18.0 and ≤38.0 kg/m2, with body weight ≥ 50 kg and no more than 140 kg
  • Laboratory values must be within normal limits (correction allowed) or considered clinically insignificant
  • Do not participate in any other clinical trials with a BRAF or other RAF inhibitors

Additional inclusion criteria for patients with normal hepatic function (Control group):

  • Absence of clinically significant deviation from normal in medical history, physical examination, vital signs, electrocardiograms and clinical laboratory determinations.
  • Must match to at least one hepatic impairment subject by age, gender and bodyweight

Additional inclusion criteria for hepatic impaired subjects:

  • Confirmed hepatic disease
  • Stable Child-Pugh status within 28 days prior to dosing.

Exclusion criteria for all subjects

  • Participation in any clinical investigation within 4 weeks prior to dosing
  • Significant acute illness within the two weeks prior to dosing
  • History of immunodeficiency diseases, including a positive HIV
  • History of malignancy of any organ system, treated or untreated, within 5 years
  • Any prior history of keratoacanthoma and/or cutaneous squamous cell carcinoma
  • A known diagnosis of any of the RASopathies, such as NF-1, Noonan syndrome, or related conditions.
  • History of drug or alcohol abuse within the 6 months prior to dosing
  • Smoking: urine cotinine levels below 500 ng/mL on Day -1.
  • Use of drugs known to affect CYP3A4 and/or CYP2C8 including both (strong or moderate) inhibitors and inducers, within 7 days prior to dosing
  • Administration of medications that prolong the QT interval within 4 weeks prior to dosing and until EOT.
  • History or current diagnosis of cardiac disease indicating significant risk of safety
  • Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of drugs.

Additional exclusion criteria for healthy subjects (control group):

  • Clinical evidence of liver disease or liver injury
  • History or presence of renal impairment as indicated by abnormal creatinine or BUN values
  • A positive Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody

Additional exclusion criteria for subjects with hepatic impairment:

  • Alcohol or drug abuse within one month prior to dosing or evidence of such
  • History of liver transplantation at any time in the past and is on immunosuppressant therapy.
  • Encephalopathy Grade 3 or worse within 28 days of dosing.
  • History of surgical portosystemic shunt.
  • Life expectancy ≤3 months

Other protocol-defined inclusion/exclusion may apply.

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: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

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.
EXPERIMENTAL: Group 1 - Control group
Drug: dabrafenib
Single dose of 100 mg dabrafenib on Day 1
Other Names:
  • DRB436
EXPERIMENTAL: Group 2-Moderate hepatic impairment
Drug: dabrafenib
Single dose of 100 mg dabrafenib on Day 1
Other Names:
  • DRB436
EXPERIMENTAL: Group 3-Severe hepatic impairment
Drug: dabrafenib
Single dose of 100 mg dabrafenib on Day 1
Other Names:
  • DRB436

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
Time Frame
Maximum plasma concentration (Cmax)
Time Frame: Predose through 96 hours postdose
Predose through 96 hours postdose
Area under the curve (AUClast)
Time Frame: Predose through 96 hours postdose
Predose through 96 hours postdose
Area under the curve (AUFinf)
Time Frame: Predose through 96 hours postdose
Predose through 96 hours postdose
Systemic drug clearance (CL/F)
Time Frame: Predose through 96 hours postdose
Predose through 96 hours postdose
Time to reach maximum concentration (Tmax)
Time Frame: Predose through 96 hours postdose
Predose through 96 hours postdose
Terminal elimination rate (Lambda_z)
Time Frame: Predose through 96 hours postdose
Predose through 96 hours postdose
Elimination half-life (T1/2)
Time Frame: Predose through 96 hours postdose
Predose through 96 hours postdose
Volume of distribution (Vz/F)
Time Frame: Predose through 96 hours postdose
Predose through 96 hours postdose

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
Time Frame
Number of subjects with adverse events
Time Frame: Time of study drug administration through 30 days postdose
Time of study drug administration through 30 days postdose
Number of subjects with abnormal lab values related to study drug
Time Frame: Time of study drug administration through 30 days postdose
Time of study drug administration through 30 days postdose
Number of subjects with abnormal blood pressure related to study drug
Time Frame: Time of study drug administration through 30 days postdose
Time of study drug administration through 30 days postdose
Number of subjects with abnormal pulse rate related to study drug
Time Frame: Time of study drug administration through 30 days postdose
Time of study drug administration through 30 days postdose
Number of subjects with abnormal respiratory rate related to study drug
Time Frame: Time of study drug administration through 30 days postdose
Time of study drug administration through 30 days postdose
Number of subjects with abnormal body temperature related to study drug
Time Frame: Time of study drug administration through 30 days postdose
Time of study drug administration through 30 days postdose
Changes in electrocardiogram (ECG)
Time Frame: Time of study drug administration through 30 days postdose
Time of study drug administration through 30 days postdose

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.
Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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.
December 20, 2016

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.
October 12, 2018

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.
April 8, 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).
August 16, 2016

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.
August 16, 2016

First Posted (ESTIMATE)

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.
August 19, 2016

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.
December 8, 2020

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.
December 6, 2020

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.
April 1, 2020

More Information

Terms related to this study

Keywords

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.
  • CDRB436A2107

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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