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Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment

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Novartis

Status and phase

Terminated
Phase 1

Conditions

Hepatic Impairment

Treatments

Drug: dabrafenib

Study type

Interventional

Funder types

Industry

Identifiers

NCT02873650
CDRB436A2107

Details and patient eligibility

About

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

Enrollment

5 patients

Sex

All

Ages

18 to 75 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose

Basic Science

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

5 participants in 3 patient groups

Group 1 - Control group
Experimental group
Treatment:
Drug: dabrafenib
Group 2-Moderate hepatic impairment
Experimental group
Treatment:
Drug: dabrafenib
Group 3-Severe hepatic impairment
Experimental group
Treatment:
Drug: dabrafenib

Trial contacts and locations

4

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Data sourced from clinicaltrials.gov

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