Comparative PK Assessment Study of Casdatifan in Moderate Hepatically Impaired Participants Versus Matched Participants With Normal Hepatic Function

Official title

A Phase 1, Open-Label, Single-Dose, Parallel-Group Study to Evaluate the Pharmacokinetics of Casdatifan (AB521) in Participants With Moderate Hepatic Impairment Compared to Healthy Matched Participants

Overview

The purpose of the study is to compare the single dose PK of casdatifan between participants with moderate hepatic impairment (HI) and healthy matched control participants with normal hepatic function.

Interventions

• Drug Casdatifan
  Participants will receive a 100 mg single oral dose of casdatifan.

Primary outcome measures

• Area under the concentration time curve, from time 0 to the last observed non-zero concentration, of casdatifan in plasma (AUC0-t) [Time frame: Up to 10 days post-dose]
• Area under the concentration time curve from time 0 extrapolated to infinity of casdatifan in plasma (AUC0-inf) [Time frame: Up to 10 days post-dose]
• Maximum observed concentration of casdatifan in plasma (Cmax) [Time frame: Up to 10 days post-dose]

Secondary outcome measures (8)

• Time to reach Cmax of casdatifan in plasma (Tmax) [Time frame: Up to 10 days post-dose]
• Apparent first order terminal elimination rate constant calculated from a semi log plot of the plasma concentration versus time curve (Kel) [Time frame: Up to 10 days post-dose]
• Percent of AUC0-inf extrapolated (AUC%extrap) [Time frame: Up to 10 days post-dose]
• Apparent first order terminal elimination half life (t½) [Time frame: Up to 10 days post-dose]
• Apparent total clearance (CL/F) [Time frame: Up to 10 days post-dose]
• Apparent total clearance (Vz/F) [Time frame: Up to 10 days post-dose]
• Unbound fraction (fu) of casdatifan [Time frame: Up to 10 days post-dose]
• Number of participants experiencing Adverse Events (AEs) [Time frame: Up to 23 days post-dose]

Eligibility criteria

Inclusion criteria

All Participants:

• Male participants must be vasectomized
• BMI ≥ 18.0 and ≤ 42.0 kg/m2 and body weight ≥ 45 kg at screening.

Participants with Moderate HI (Group 1)

• Is classified as having moderate HI by the Child-Pugh classification system (Class B, score of 7 to 9, inclusive) at screening.
• 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 screening

Healthy Participants:

• Healthy with no clinically significant medical history, physical examination, clinical laboratory profiles, vital signs, and ECGs, as deemed by the PI or designee

Exclusion criteria

All Participants:

• Participants with Gilbert's syndrome.

Participants with Moderate HI (Group 1):

• Positive for HBsAg or HCV Ab, and detectable viral load at screening.
• Severe complications of liver disease within the preceding 3 months of screening.
• Fluctuating or rapidly deteriorating hepatic function from screening until prior to dosing, in the opinion of the PI or designee.

Healthy Control Participants:

• History or presence of clinically significant medical or psychiatric condition or disease, or presence of any illness that, in the opinion of the PI or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07751250 · ARC-521-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗