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

Sponsor

Arcus Biosciences, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT05154136

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Days)

22.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Participants	Drug: Etrumadenant Drug: Itraconazole	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

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.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)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Oct 27, 2021

Actual Primary Completion Date :

Nov 10, 2021

Actual Study Completion Date :

Nov 23, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Etrumadenant then Etrumadenant + Itraconazole 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 Capsule Other Names: AB928 Drug: Itraconazole Capsule

Arm

Intervention/Treatment

Experimental: Etrumadenant then Etrumadenant + Itraconazole

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

Capsule

Other Names:

AB928

Drug: Itraconazole

Capsule

Outcome Measures

Primary Outcome Measures

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

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 [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 55 Years

Sexes Eligible for Study:

All

Accepts 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.