Clinical trial NCT05154136: A Drug-Drug Interaction Study to Evaluate the Effect of Itraconazole on the Pharmacokinetic Profile of Etrumadenant in Healthy Adult Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Participants
Keywords: Etrumadenant
Itraconazole
Healthy participants
Pharmacokinetics
Drug-Drug Interaction
AB928
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-10
Enrollment: 20
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
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.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Etrumadenant Administered With or Without Itraconazole
timeFrame: 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
measure: 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
timeFrame: 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
measure: Area Under the Plasma Concentration Time Curve From Time '0' Extrapolated to Infinity [AUC(0-inf)] of Etrumadenant Administered With or Without Itraconazole
timeFrame: 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 outcomes:
measure: Percentage of AUC(0-inf) Extrapolation (AUC%extrap) of Etrumadenant Administered With or Without Itraconazole
timeFrame: 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
measure: Apparent Total Plasma Clearance (CL/F) of Etrumadenant Administered With or Without Itraconazole
timeFrame: 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
measure: Time to Cmax (Tmax) of Etrumadenant Administered With or Without Itraconazole
timeFrame: 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
measure: Apparent First-order Terminal Elimination Rate Constant (Kel) of Etrumadenant Administered With or Without Itraconazole
timeFrame: 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
measure: Apparent First Order Terminal Elimination Half-life (t1/2) of Etrumadenant Administered With or Without Itraconazole
timeFrame: 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
measure: Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Etrumadenant Administered With or Without Itraconazole
timeFrame: 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
measure: Cmax of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole
timeFrame: 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
measure: AUC(0-t) of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole
timeFrame: 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
measure: AUC(0-inf) of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole
timeFrame: 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
measure: AUC%extrap of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole
timeFrame: 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
measure: CL/F of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole
timeFrame: 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
measure: Tmax of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole
timeFrame: 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
measure: Kel of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole
timeFrame: 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
measure: t1/2 of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole
timeFrame: 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
measure: Vz/F of Etrumadenant Metabolites When Etrumadenant is Administered With or Without Itraconazole
timeFrame: 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
measure: Number of Participants with Treatment Emergent Adverse Events
timeFrame: Up to 30 days
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Arcus Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: