Clinical trial NCT05277012: A Study to Evaluate Pharmacokinetics (PK) of Etrumadenant Tablet and Capsule Formulations in Healthy Adult Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Etrumadenant
Healthy participants
Pharmacokinetics
AB928
Tablet
Capsule
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Gilead Sciences
First posted: 2022-03-14
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: The study participants will receive 3 treatments (Treatment A, B and C) sequentially during the Treatment Period 1, 2, and 3.

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.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Etrumadenant
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From 0 to Last Observed Non-zero Concentration [AUC(0-t)] of Etrumadenant
timeFrame: 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
measure: Area Under the Plasma Concentration Time Curve From Time '0' Extrapolated to Infinity [AUC(0-inf)] of Etrumadenant
timeFrame: 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
measure: Time to Cmax (Tmax) of Etrumadenant
timeFrame: 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
measure: Apparent First-order Terminal Elimination Rate Constant (Kel) of Etrumadenant
timeFrame: 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
measure: Percentage of AUC(0-inf) Extrapolation (AUC%extrap) of Etrumadenant
timeFrame: 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
measure: Apparent First Order Terminal Elimination Half-life (t1/2) of Etrumadenant
timeFrame: 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
measure: Apparent Total Plasma Clearance (CL/F) of Etrumadenant
timeFrame: 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
measure: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Etrumadenant
timeFrame: 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
measure: Ratio of Etrumadenant metabolites to Etrumadenant
timeFrame: 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
measure: Ratio of Etrumadenant metabolites to Total Metabolite Concentration
timeFrame: 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 outcomes:
measure: Number of Participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to 4 months
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Investigational Site
state: Nebraska
Study officials:
affiliation: Arcus Biosciences
name: Medical Director
role: STUDY_DIRECTOR
References: