Pharmacokinetics of Dabrafenib in Subjects With Hepatic Impairment

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.