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

Healthy Participants Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05154136
• Other study ID #: ARC-18
• Status: Completed
• Phase: Phase 1
• Start date: October 20, 2021
• Est. completion date: December 10, 2021

Study information

• Verified date: May 2024
• Source: Arcus Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 10, 2021
• Est. primary completion date: December 10, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 19 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• Etrumadenant
Capsule
• Itraconazole
Capsule

Locations

Country	Name	City	State
United States	Celerion	Lincoln	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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