A Study to Evaluate Pharmacokinetics (PK) of Etrumadenant Tablet and Capsule Formulations in Healthy Adult Participants

A Phase 1, Open-label, Randomized, Single-dose, Three-treatment, Three-way Crossover Pharmacokinetic Study to Evaluate the Relative Bioavailability of Etrumadenant (AB928) Tablet and Capsule Formulations and Food Effect on the Pharmacokinetics of the Tablet Formulation in Healthy Adult Participants

This study will compare the pharmacokinetics (PK) effect of single-dose etrumadenant tablet and capsule formulations in fasted conditions. The effect of food on single-dose PK of tablet formulation will also be assessed.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Investigational Site

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 (non-childbearing potential), 19-55 years of age, inclusive, at the screening visit.
• Body mass index (BMI) between 18.0 and 32.0 kilograms/m^2 inclusive, at screening.
• Healthy as determined by medical history, physical examination, vital signs, and ECG assessed at the screening visit.
• 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 greater than (>) 3 months prior to the first dosing] based on participant self-reporting.
• Able to swallow multiple capsules or tablets.

Exclusion Criteria:

• Participants who have a clinically relevant history or presence of respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, rheumatological, dermatological, endocrine, connective tissue diseases or disorders, in the opinion of the PI or designee.
• Have a clinically relevant surgical history, in the opinion of the PI or designee.
• History of relevant atopy or hypersensitivity to etrumadenant or related compounds.
• History or presence of alcohol or drug abuse within the past 2 years prior to the first dosing.
• History (within 3 months of screening visit) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 g of alcohol [equivalent to approximately 8 oz of beer (5.5% alcohol); 1 oz of 45% alcohol; or 3.5 oz of wine (12% alcohol)] based on self-reporting.
• Have a significant infection or known inflammatory process upon screening or check in, in the opinion of the PI or designee.
• Have acute gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea, heartburn) at the time of screening or check in.
• Female participants of childbearing potential.
• Positive results for hepatitis B, C, HIV-1 or HIV-2.
• Clinically significant hypokalemia in the opinion of the PI or designee.
• Have been on a diet incompatible with the on study diet, in the opinion of the PI or designee, within the 30 days prior to the first dosing.
• Donation of blood or significant blood loss within 56 days prior to the first dosing.
• Plasma donation within 7 days prior to the first dosing.
• Participation in another clinical study within 30 days prior to the first dosing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment sequence ABC; Participants will be sequentially administered with Treatment A, B then C (Treatment A: etrumadenant capsule in fasted state; Treatment B: etrumadenant tablet in fasted state; Treatment C: etrumadenant tablet in fed state). Each treatment will be separated by a washout period of 7 days.	Drug: Etrumadenant; Etrumadenant capsule and tablet formulations; Other Names: AB928
Experimental: Treatment sequence BCA; Participants will be sequentially administered with Treatment B, C then A. Each treatment will be separated by a washout period of 7 days.	Drug: Etrumadenant; Etrumadenant capsule and tablet formulations; Other Names: AB928
Experimental: Treatment sequence CAB; Participants will be sequentially administered with Treatment C, A then B. Each treatment will be separated by a washout period of 7 days.	Drug: Etrumadenant; Etrumadenant capsule and tablet formulations; Other Names: AB928

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Area Under the Plasma Concentration-time Curve From 0 to Last Observed Non-zero Concentration [AUC(0-t)] of Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Area Under the Plasma Concentration Time Curve From Time '0' Extrapolated to Infinity [AUC(0-inf)] of Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Time to Cmax (Tmax) of Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Apparent First-order Terminal Elimination Rate Constant (Kel) of Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Percentage of AUC(0-inf) Extrapolation (AUC%extrap) of Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Apparent First Order Terminal Elimination Half-life (t1/2) of Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Apparent Total Plasma Clearance (CL/F) of Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Ratio of Etrumadenant metabolites to Etrumadenant	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3
Ratio of Etrumadenant metabolites to Total Metabolite Concentration	Multiple timepoint evaluations from pre-dose to 24 hours post-dose at Days 1, 2, 3, 4, 5, and 6 during Treatment Period 1, 2 and 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment Emergent Adverse Events (TEAEs)	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 4 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2022
• Primary Completion (Actual): March 31, 2022
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: January 31, 2022
• First Submitted That Met QC Criteria: March 11, 2022
• First Posted (Actual): March 14, 2022

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; Capsule; Tablet; Etrumadenant; AB928
• Other Study ID Numbers: ARC-23

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