Study to Investigate the Safety, Tolerability, and Pharmacokinetic Profile With Oral AB521 in Healthy Volunteers

Healthy Participants Clinical Trial

— ARC-14  

Official title:

A First-in-human, Participant and Investigator-blinded, Randomized, Placebo-controlled, Single-and Multiple-Ascending Dose Study With Drug-Drug Interaction, to Investigate the Safety, Tolerability, and Pharmacokinetic Profile of AB521, in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05117554
• Other study ID #: ARC-14
• Secondary ID: 2021-003856-17
• Status: Completed
• Phase: Phase 1
• Start date: November 9, 2021
• Est. completion date: February 17, 2023

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 safety and tolerability, pharmacokinetic, and pharmacodynamic profile, and drug-drug interaction (DDI) of AB521 in healthy participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: February 17, 2023
• Est. primary completion date: February 17, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Participants who are healthy volunteers (in the opinion of the investigator) as determined by pre-study medical history, physical examination, vital signs, and 12-lead electrocardiogram (ECG)

• All clinical laboratory tests of blood and urine must be within the normal range or show no clinically relevant excursions from the normal range as judged by Principal Investigator at screening and admission.

• Screening and randomization hemoglobin =for males and females is as follows:

• SAD: male and female hemoglobin level = 12.5 grams/ deciliters (g/dL) (7.7 millimoles/liters [mmol/L])

• MAD and DDI: male hemoglobin level = 14.2 g/dL (8.8 mmol/L) and female hemoglobin level = 12.5 g/dL (7.7 mmol/L).

• Participants should have adequate peripheral venous access.

• Body weight of 45 kilograms (kg) or greater and body mass index within the range of 18 to 32 kg/meters squared (m^2) (inclusive)

• Male participants must be vasectomized and have been vasectomized for at least 3 months prior to screening visit with confirmed history of azoospermia subsequent to the vasectomy procedure

• Contraceptive use should be consistent with local regulations

Exclusion Criteria:

• Has any (acute or chronic [including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection]) medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the study participant's ability to participate in this study

• Has history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, cerebrovascular, neurological, or other major disorders capable of significantly altering the absorption, metabolism, or elimination of investigational drug; constituting a risk when taking the study intervention; or interfering with the interpretation of data in the opinion of the investigator

• Abnormal blood pressure (BP) or pulse measurements at the Screening Visit or Day -2/-1 (Admission) in a supine position after 5 minutes of rest as follows: mean systolic BP =139 millimeters of mercury (mm Hg) or mean diastolic BP =89 mm Hg; mean pulse < 40 beats per minute (bpm) or > 100 bpm.

• Liver enzyme test results: Alanine aminotransferase, aspartate aminotransferase, bilirubin, or alkaline phosphatase >1.0x the upper limit of normal

• Current or chronic history of liver disease or known hepatic or biliary abnormalities

• Has 12-lead electrocardiogram with changes considered to be clinically significant at the Screening Visit or day of admission

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• AB521
Capsule
• Placebo
Capsule
• Midazolam
Syrup solution

Locations

Country	Name	City	State
Netherlands	Investigational Site	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
Arcus Biosciences, Inc.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)		Up to 21.5 Weeks
Primary	Number of Participants With Abnormal Changes From Baseline in Laboratory Parameter Values		Baseline; Up to 21.5 Weeks
Primary	Number of Participants With Abnormal Changes from Baseline in Vital Sign Values		Baseline; Up to 21.5 Weeks
Primary	Maximum Observed Plasma Concentration (Cmax) of AB521		multiple timepoints up to approximately 21.5 Weeks
Primary	Area Under the Plasma Concentration Time Curve From Hour 0 to the Last Sample With Measurable Plasma Concentrations (AUClast) of AB521		multiple timepoints up to approximately 21.5 Weeks
Primary	Time of Occurrence of Cmax (tmax) of AB521		multiple timepoints up to approximately 21.5 Weeks
Primary	Apparent Terminal Elimination Rate Constant (?z) of AB521		multiple timepoints up to approximately 21.5 Weeks
Primary	Terminal Half-Life (t1/2) of AB521		multiple timepoints up to approximately 21.5 Weeks
Primary	Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUCinf) of AB521		multiple timepoints up to approximately 21.5 Weeks
Primary	Apparent Volume of Distribution of AB521		multiple timepoints up to approximately 21.5 Weeks
Primary	Apparent Total Body Clearance of AB521		multiple timepoints up to approximately 21.5 Weeks
Secondary	Maximum Observed Plasma Concentration (Cmax) of midazolam and 1 hydroxymidazolam		multiple timepoints up to approximately 21.5 Weeks
Secondary	Area Under the Plasma Concentration Time Curve From Hour 0 to the Last Sample With Measurable Plasma Concentrations (AUClast) of midazolam and 1 hydroxymidazolam		multiple timepoints up to approximately 21.5 Weeks
Secondary	Time of Occurrence of Cmax (tmax) of midazolam and 1 hydroxymidazolam		multiple timepoints up to approximately 21.5 Weeks
Secondary	Apparent Terminal Elimination Rate Constant (?z) of midazolam and 1 hydroxymidazolam		multiple timepoints up to approximately 21.5 Weeks
Secondary	Terminal Half-Life (t1/2) of midazolam and 1 hydroxymidazolam		multiple timepoints up to approximately 21.5 Weeks
Secondary	Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUCinf) of midazolam and 1 hydroxymidazolam		multiple timepoints up to approximately 21.5 Weeks
Secondary	Apparent Volume of Distribution of midazolam and 1 hydroxymidazolam		multiple timepoints up to approximately 21.5 Weeks
Secondary	Apparent Total Body Clearance of midazolam and 1 hydroxymidazolam		multiple timepoints up to approximately 21.5 Weeks