Pharmacokinetics (PK) and Safety of Zanzalintinib in Participants With Moderate Hepatic Impairment (HI)

Phase 1

Not yet recruiting

• Conditions: Hepatic Impairment; Moderate Hepatic Impairment
• Interventions: Drug: Zanzalintinib

• Registration Number: NCT06962332
• Lead Sponsor: Exelixis

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-30
• Study First Submitted QC: 2025-04-30
• Last Update Submitted: 2025-04-30
• Study Start: 2025-05
• Study First Posted: 2025-05-08
• Last Update Posted: 2025-05-08
• Primary Completion: 2025-12
• Study Completion: 2026-04

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Moderate HI	Zanzalintinib	Participants with moderate HI will receive a single oral dose of zanzalintinib tablet on Day 1.
Matched Healthy Control	Zanzalintinib	Matched healthy control participants will receive a single oral dose of zanzalintinib tablet on Day 1.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Up to 30 days