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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: Etrumadenant
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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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.

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
Intervention Model: Sequential Assignment
Interventional Model Description: The study consists of 2 periods with participants sequentially receiving Treatment A (etrumadenant) in Period 1, followed by Treatment B (etrumadenant + itraconazole) in Period 2.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etrumadenant then Etrumadenant + Itraconazole<br>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<br>* Capsule<br>* Other names: AB928;Drug: Itraconazole<br>* Capsule<br>|

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 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Etrumadenant, Itraconazole, Healthy participants, Pharmacokinetics, Drug-Drug Interaction, AB928