Drug-Drug Interaction Study of Casdatifan in Healthy Adult Participants (ARC-29)

A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study of Casdatifan With Itraconazole (Strong CYP3A4 Inhibitor) and Phenytoin (Strong CYP3A4 Inducer) in Healthy Adult Participants

The purpose of the study is to assess the effects of multiple doses of itraconazole (a strong CYP3A4 inhibitor) on single dose PK of casdatifan in healthy adults and to assess the effects of multiple doses of phenytoin (a strong CYP3A4 inducer) on single dose PK of casdatifan in healthy adults.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Casdatifan; Drug: Itraconazole; Drug: Phenytoin

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy, adult, male or female 18-55 years of age, inclusive, at the screening visit.
• Male participants must be vasectomized
• Continuous non-smoker who has not used nicotine- and tobacco-containing products for at least 3 months prior to the first dosing based on participant self-reporting.
• BMI ≥ 18.0 and ≤ 32.0 kg/m2 and body weight ≥ 45 kg, at the screening visit
• Able to swallow multiple tablets and/or capsules.

Exclusion Criteria:

• Is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee.
• History 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.
• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.
• History of asthma or chronic obstructive pulmonary disease (including childhood), clinically significant food allergies or anaphylaxis, as deemed by PI or designee.

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Casdatifan-Itraconazole-Phenytoin; Participants will receive casdatifan, itraconazole, and phenytoin.	Drug: Casdatifan; Administered as a single dose in treatment Periods 1, 2, and 3; Drug: Itraconazole; Administered as multiple doses in treatment Period 2; Drug: Phenytoin; Administered as multiple doses in treatment Period 3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Plasma Drug Concentration-Time Curve (AUC) for casdatifan	Up to 168 hours post dose for Period 1; up to 216 hours post dose for Period 2; and up to 120 hours post dose for Period 3
Maximum Concentration (Cmax) in Plasma for casdatifan	Up to 168 hours post dose for Period 1; up to 216 hours post dose for Period 2; and up to 120 hours post dose for Period 3
Time to Maximum Concentration (Tmax) in Plasma for casdatifan	Up to 168 hours post dose for Period 1; up to 216 hours post dose for Period 2; and up to 120 hours post dose for Period 3

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentration observed at the end of the dosing interval (Ctrough) for itraconazole (Period 2) and phenytoin (Period 3)	Up to 18 days
Number of Participants with Treatment Emergent Adverse Events (TEAEs)	Up to 26.2 weeks

Collaborators and Investigators

• Sponsor: Arcus Biosciences, Inc.
• Investigators: Study Director: Medical Director, Arcus Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2025
• Primary Completion (Actual): October 18, 2025
• Study Completion (Actual): October 18, 2025

Study Registration Dates

• First Submitted: March 27, 2025
• First Submitted That Met QC Criteria: April 2, 2025
• First Posted (Actual): April 9, 2025

Study Record Updates

• Last Update Posted (Estimated): November 13, 2025
• Last Update Submitted That Met QC Criteria: November 12, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: AB521; HIF-2α; hypoxia-inducible factor 2 alpha; Casdatifan
• Additional Relevant MeSH Terms: Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Imidazoles; Triazoles; Piperazines; Hydantoins; Imidazolidines; Itraconazole; Phenytoin
• Other Study ID Numbers: ARC-29

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No