Hepatic Impairment, Moderate Hepatic Impairment
Conditions
Keywords
Zanzalintinib, Pharmacokinetics
Brief summary
The primary purpose of this study is to evaluate the plasma PK of zanzalintinib following a single dose in participants with moderate liver dysfunction compared to matched healthy participants with normal liver function.
Interventions
DRUGZanzalintinib
Administered as specified in the treatment arm.
Sponsors
Exelixis
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * All Participants: * No clinically significant medical history (aside from the HI for participants in the HI group only), physical examination findings, or vital signs, as deemed by the investigator. * A continuous non-smoker or moderate smoker who smokes ≤ 10 cigarettes, ≤ 2 cigars, or ≤2 pipes per day and agree to limit smoking during the confinement period to ≤ 4 cigarettes or ≤1 cigar or pipe per day. Participant must agree to maintain the same smoking status (smoker or non-smoker) from screening and until after the last PK sample collection. * Has not donated blood within 30 days of dosing or plasma within 7 days of dosing and must agree to refrain from blood donation until at least 30 days following dosing. * Participants with Moderate HI Only: * Adequate bone marrow function, at the screening and dosing visit. * Is classified as having moderate HI by the Child-Pugh classification system (Class B, score of 7 to 9, inclusive) and has a total bilirubin value within the range of \> 1.5\* upper limit of normal (ULN) and ≤ 3\* ULN at the screening and dosing visit. * Has a diagnosis of chronic (\> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency at the screening visit with features of cirrhosis due to any etiology. * Healthy Control Participants Only: * Age must be within ± 10 years of the mean age of participants with moderate HI. The sex ratio (male/female ratio), and smoking status ratio (smokers/non-smokers ratio) must be the same to the sex and smoking status ratio of participants with moderate HI. Key
Exclusion criteria
* All Participants: * • History of any medical or surgical conditions that would potentially alter absorption, distribution, metabolism, and/or excretion of orally administered drugs. * Has or is at risk for major cardiac events or dysfunction. * Participants with Moderate HI Only: * History of liver or other solid organ transplant. * Fluctuating or rapidly deteriorating hepatic function (the definition of the change of more than 1 Child-Pugh point) within 30 days prior to Day 1, in the opinion of the investigator and Sponsor. * Symptoms or history of Grade 3 or worse degree of encephalopathy within 3 months of dosing. * Clinical evidence of severe ascites at the screening visit or at check in. * Healthy Control Participants Only: * History or presence of alcohol or drug abuse within the past 2 years prior to dosing. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time t Corresponding to the Last Quantifiable Concentration (AUC0-t) of Zanzalintinib | Predose up to 7 days postdose |
| Maximum Observed Plasma Drug Concentration (Cmax) of Zanzalintinib | Predose up to 7 days postdose |
| Time to Cmax (Tmax) of Zanzalintinib | Predose up to 7 days postdose |
Secondary
| Measure | Time frame |
|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Up to 30 days |
Countries
United States
Contacts
Primary ContactExelixis Clinical Trials
Backup ContactBackup or International
Outcome results
None listed