Clinical trial NCT06962332: Pharmacokinetics (PK) and Safety of Zanzalintinib in Participants With Moderate Hepatic Impairment (HI)
Official title: A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Zanzalintinib in Participants With Moderate Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Hepatic Impairment
Moderate Hepatic Impairment
Keywords: Zanzalintinib
Pharmacokinetics
Lead sponsor: Exelixis
Sponsor class: INDUSTRY
First posted: 2025-05-08
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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/Exclusion criteria may apply.

Primary outcomes:
measure: Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Time t Corresponding to the Last Quantifiable Concentration (AUC0-t) of Zanzalintinib
timeFrame: Predose up to 7 days postdose
measure: Maximum Observed Plasma Drug Concentration (Cmax) of Zanzalintinib
timeFrame: Predose up to 7 days postdose
measure: Time to Cmax (Tmax) of Zanzalintinib
timeFrame: Predose up to 7 days postdose
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 30 days
Other outcomes:
Locations:
Study officials:
affiliation: Exelixis
name: Medical Director
role: STUDY_DIRECTOR
References: