Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment

• Status: Terminated
• Trial end date: 2019-04-08
• Target enrollment: 0
• Participant gender: All

Summary

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

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Dabrafenib

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.