Healthy Participants
Conditions
Keywords
Etrumadenant, Itraconazole, Healthy participants, Pharmacokinetics, Drug-Drug Interaction, AB928
Brief summary
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.
Interventions
DRUGEtrumadenant
Capsule
DRUGItraconazole
Capsule
Sponsors
Arcus Biosciences, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
19 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
| 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 | — |
| Number of Participants with Treatment Emergent Adverse Events | Up to 30 days | Safety will be assessed by monitoring adverse events and clinically significant changes in 12 lead Electrocardiogram, vital signs, and clinical laboratory tests results. |
| 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 | — |
| 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 | — |
| 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 | — |
Countries
United States
Outcome results
None listed