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Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT02873650
Collaborator
(none)
5
Enrollment
4
Locations
3
Arms
27.6
Actual Duration (Months)
1.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
5 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
open-label, parallel groupopen-label, parallel group
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
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
Actual Study Start Date :
Dec 20, 2016
Actual Primary Completion Date :
Oct 12, 2018
Actual Study Completion Date :
Apr 8, 2019

Arms and Interventions

Arm Intervention/Treatment
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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Maximum plasma concentration (Cmax) [Predose through 96 hours postdose]

    2. Area under the curve (AUClast) [Predose through 96 hours postdose]

    3. Area under the curve (AUFinf) [Predose through 96 hours postdose]

    4. Systemic drug clearance (CL/F) [Predose through 96 hours postdose]

    5. Time to reach maximum concentration (Tmax) [Predose through 96 hours postdose]

    6. Terminal elimination rate (Lambda_z) [Predose through 96 hours postdose]

    7. Elimination half-life (T1/2) [Predose through 96 hours postdose]

    8. Volume of distribution (Vz/F) [Predose through 96 hours postdose]

    Secondary Outcome Measures

    1. Number of subjects with adverse events [Time of study drug administration through 30 days postdose]

    2. Number of subjects with abnormal lab values related to study drug [Time of study drug administration through 30 days postdose]

    3. Number of subjects with abnormal blood pressure related to study drug [Time of study drug administration through 30 days postdose]

    4. Number of subjects with abnormal pulse rate related to study drug [Time of study drug administration through 30 days postdose]

    5. Number of subjects with abnormal respiratory rate related to study drug [Time of study drug administration through 30 days postdose]

    6. Number of subjects with abnormal body temperature related to study drug [Time of study drug administration through 30 days postdose]

    7. Changes in electrocardiogram (ECG) [Time of study drug administration through 30 days postdose]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes

    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 American Institute of Research Los Angeles California United States 900017
    2 Omega Research Consultants LLC DeBary Florida United States 32713
    3 Hassman Research Institute Berlin New Jersey United States 08009
    4 Wake Research Associates Oncology Raleigh North Carolina United States 27612

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT02873650
    Other Study ID Numbers:
    • CDRB436A2107
    First Posted:
    Aug 19, 2016
    Last Update Posted:
    Dec 8, 2020
    Last Verified:
    Apr 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Hepatic impairment
    Healthy volunteers
    Clinical pharmacology study
    DRB436
    dabrafenib
    normal hepatic function
    impaired hepatic function
    Additional relevant MeSH terms:
    Liver Diseases
    Dabrafenib

    Study Results

    No Results Posted as of Dec 8, 2020