Hepatic Impairment
Conditions
Keywords
Hepatic impairment, Healthy volunteers, Clinical pharmacology study, DRB436, dabrafenib, normal hepatic function, impaired hepatic function
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.
Interventions
DRUGdabrafenib
Single dose of 100 mg dabrafenib on Day 1
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
open-label, parallel group
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Volume of distribution (Vz/F) | Predose through 96 hours postdose |
| Maximum plasma concentration (Cmax) | Predose through 96 hours postdose |
| Area under the curve (AUClast) | Predose through 96 hours postdose |
| Area under the curve (AUFinf) | Predose through 96 hours postdose |
| Systemic drug clearance (CL/F) | Predose through 96 hours postdose |
| Time to reach maximum concentration (Tmax) | Predose through 96 hours postdose |
| Terminal elimination rate (Lambda_z) | Predose through 96 hours postdose |
| Elimination half-life (T1/2) | Predose through 96 hours postdose |
Secondary
| Measure | Time frame |
|---|---|
| Number of subjects with abnormal lab values related to study drug | Time of study drug administration through 30 days postdose |
| Number of subjects with abnormal blood pressure related to study drug | Time of study drug administration through 30 days postdose |
| Number of subjects with abnormal pulse rate related to study drug | Time of study drug administration through 30 days postdose |
| Number of subjects with abnormal respiratory rate related to study drug | Time of study drug administration through 30 days postdose |
| Number of subjects with abnormal body temperature related to study drug | Time of study drug administration through 30 days postdose |
| Changes in electrocardiogram (ECG) | Time of study drug administration through 30 days postdose |
| Number of subjects with adverse events | Time of study drug administration through 30 days postdose |
Countries
United States
Outcome results
None listed