A Drug-Drug Interaction Study to Evaluate the Effect of Itraconazole on the Pharmacokinetic Profile of Etrumadenant in Healthy Adult Participants

A Phase 1, Open-Label, 2-period Drug-Drug Interaction Study to Investigate the Effect of Multiple Doses of Itraconazole on the Single-Dose Pharmacokinetic Profile of AB928 in Healthy Adult Participants

This study will evaluate the effect of multiple oral doses of itraconazole, on the pharmacokinetics of etrumadenant when etrumadenant is administered as a single dose in healthy adult participants.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy, adult, male or female (of non-childbearing potential), at the screening visit
• Body mass index between 18 and 32 kilograms/m^2 inclusive, at screening
• Healthy as determined by pre-study medical history, physical examination, vital signs, complete neurological examination and 12-lead ECG
• Clinical laboratory test results clinically acceptable at screening and check-in
• Non-smokers or ex-smokers (must have ceased smoking and stopped using nicotine containing products >3 months prior to the first dosing) based on participant self-reporting

Exclusion Criteria:

• Participants who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, rheumatological, endocrine, connective tissue diseases or disorders
• Have a clinically relevant surgical history in the opinion of the principal investigator or designee
• Have a history of relevant atopy or hypersensitivity to the study drugs or related compounds (e.g., allergy to itraconazole or other azole antifungals
• History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing

Note: This is not an exhaustive list of criterias.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Etrumadenant then Etrumadenant + Itraconazole; Participants will receive the Treatment A (etrumadenant) followed by Treatment B (etrumadenant + itraconazole). A washout period of 5 days will be maintained between the two treatments.	Drug: Etrumadenant; Capsule; Other Names: AB928; Drug: Itraconazole; Capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Etrumadenant Administered With or Without Itraconazole	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Area Under the Plasma Concentration-time Curve From 0 to Last Observed Non-zero Concentration [AUC(0-t)] of Etrumadenant Administered With or Without Itraconazole	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Area Under the Plasma Concentration Time Curve From Time '0' Extrapolated to Infinity [AUC(0-inf)] of Etrumadenant Administered With or Without Itraconazole	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of AUC(0-inf) Extrapolation (AUC%extrap) of Etrumadenant Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Apparent Total Plasma Clearance (CL/F) of Etrumadenant Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Time to Cmax (Tmax) of Etrumadenant Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Apparent First-order Terminal Elimination Rate Constant (Kel) of Etrumadenant Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Apparent First Order Terminal Elimination Half-life (t1/2) of Etrumadenant Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Etrumadenant Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Cmax of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
AUC(0-t) of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
AUC(0-inf) of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
AUC%extrap of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
CL/F of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Tmax of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Kel of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
t1/2 of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Vz/F of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole		Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Period 1; and Days 5, 6, 7, 9, and 11 during Period 2
Number of Participants with Treatment Emergent Adverse Events	Safety will be assessed by monitoring adverse events and clinically significant changes in 12 lead Electrocardiogram, vital signs, and clinical laboratory tests results.	Up to 30 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Actual): December 10, 2021
• Study Completion (Actual): December 10, 2021

Study Registration Dates

• First Submitted: October 16, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 8, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy participants; Itraconazole; Drug-Drug Interaction; Etrumadenant; AB928
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole
• Other Study ID Numbers: ARC-18

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.

For more information, please visit our website.

• 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