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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: Etrumadenant


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment sequence ABC<br>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<br>* Etrumadenant capsule and tablet formulations<br>* Other names: AB928;|
| Experimental: Treatment sequence BCA<br>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<br>* Etrumadenant capsule and tablet formulations<br>* Other names: AB928;|
| Experimental: Treatment sequence CAB<br>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<br>* Etrumadenant capsule and tablet formulations<br>* Other names: AB928;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AB928, Etrumadenant, Healthy participants, Pharmacokinetics, Tablet, Capsule