Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment

NCT ID: NCT02873650

Last Updated: 2020-12-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

5 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-20

Study Completion Date

2019-04-08

Brief Summary

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

Detailed Description

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Conditions

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Hepatic Impairment

Keywords

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Hepatic impairment Healthy volunteers Clinical pharmacology study DRB436 dabrafenib normal hepatic function impaired hepatic function

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

open-label, parallel group
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Group 1 - Control group

Group Type EXPERIMENTAL

dabrafenib

Intervention Type DRUG

Single dose of 100 mg dabrafenib on Day 1

Group 2-Moderate hepatic impairment

Group Type EXPERIMENTAL

dabrafenib

Intervention Type DRUG

Single dose of 100 mg dabrafenib on Day 1

Group 3-Severe hepatic impairment

Group Type EXPERIMENTAL

dabrafenib

Intervention Type DRUG

Single dose of 100 mg dabrafenib on Day 1

Interventions

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dabrafenib

Single dose of 100 mg dabrafenib on Day 1

Intervention Type DRUG

Other Intervention Names

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DRB436

Eligibility Criteria

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Inclusion Criteria

* 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


* 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


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

Exclusion Criteria

* 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.


* 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


* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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American Institute of Research

Los Angeles, California, United States

Site Status

Omega Research Consultants LLC

DeBary, Florida, United States

Site Status

Hassman Research Institute

Berlin, New Jersey, United States

Site Status

Wake Research Associates Oncology

Raleigh, North Carolina, United States

Site Status

Countries

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United States

Related Links

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Other Identifiers

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CDRB436A2107

Identifier Type: -

Identifier Source: org_study_id