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

NCT05117554 | Completed Phase 1

• 2 other identifiers: ARC-142021-003856-17
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and tolerability, pharmacokinetic, and pharmacodynamic profile, and drug-drug interaction (DDI) of casdatifan in healthy participants.

Conditions

Healthy Participants

Keywords

AB521; HIF-2α; hypoxia-inducible factor 2 alpha; Single ascending dose (SAD); Multiple ascending dose (MAD); Drug-drug interaction (DDI); casdatifan

Outcome Measures

Primary Outcomes (11)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Up to 21.5 Weeks

• Number of Participants With Abnormal Changes From Baseline in Laboratory Parameter Values

  Baseline; Up to 21.5 Weeks

• Number of Participants With Abnormal Changes from Baseline in Vital Sign Values

  Baseline; Up to 21.5 Weeks

• Maximum Observed Plasma Concentration (Cmax) of casdatifan

  multiple timepoints up to approximately 21.5 Weeks

• Area Under the Plasma Concentration Time Curve From Hour 0 to the Last Sample With Measurable Plasma Concentrations (AUClast) of casdatifan

  multiple timepoints up to approximately 21.5 Weeks

• Time of Occurrence of Cmax (tmax) of casdatifan

  multiple timepoints up to approximately 21.5 Weeks

• Apparent Terminal Elimination Rate Constant (λz) of casdatifan

  multiple timepoints up to approximately 21.5 Weeks

• Terminal Half-Life (t1/2) of casdatifan

  multiple timepoints up to approximately 21.5 Weeks

• Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUCinf) of casdatifan

  multiple timepoints up to approximately 21.5 Weeks

• Apparent Volume of Distribution of casdatifan

  multiple timepoints up to approximately 21.5 Weeks

• Apparent Total Body Clearance of casdatifan

  multiple timepoints up to approximately 21.5 Weeks

Secondary Outcomes (8)

• Maximum Observed Plasma Concentration (Cmax) of midazolam and 1 hydroxymidazolam

  multiple timepoints up to approximately 21.5 Weeks

• 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

• Time of Occurrence of Cmax (tmax) of midazolam and 1 hydroxymidazolam

  multiple timepoints up to approximately 21.5 Weeks

• Apparent Terminal Elimination Rate Constant (λz) of midazolam and 1 hydroxymidazolam

  multiple timepoints up to approximately 21.5 Weeks

• Terminal Half-Life (t1/2) of midazolam and 1 hydroxymidazolam

  multiple timepoints up to approximately 21.5 Weeks

Study Arms (9)

SAD-casdatifan Dose 1

EXPERIMENTAL

Participants will receive "Dose 1" of casdatifan orally with water under fasting conditions.

Drug: casdatifan

SAD-casdatifan Dose 2

EXPERIMENTAL

Participants will receive "Dose 2" of casdatifan orally with water under fasting conditions.

Drug: casdatifan

SAD-casdatifan Dose 3

EXPERIMENTAL

Participants will receive "Dose 3" of casdatifan orally with water under fasting conditions.

Drug: casdatifan

SAD-casdatifan Dose 4

EXPERIMENTAL

Participants will receive "Dose 4" of casdatifan orally with water under fasting conditions.

Drug: casdatifan

SAD-Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo orally with water under fasting conditions.

Drug: Placebo

MAD-casdatifan Dose 1

EXPERIMENTAL

Participants will receive "Dose 1" of casdatifan orally with water under fasting conditions.

Drug: casdatifan

MAD-casdatifan Dose 2

EXPERIMENTAL

Participants will receive "Dose 2" of casdatifan orally with water under fasting conditions.

Drug: casdatifan

MAD-Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo orally with water under fasting conditions.

Drug: Placebo

DDI-casdatifan Dose + Midazolam

EXPERIMENTAL

Participants will receive highest safe dose level of casdatifan from MAD and midazolam orally with water under fasting conditions

Drug: casdatifan; Drug: Midazolam

Interventions

casdatifan DRUG

Capsule

Also known as: AB521

DDI-casdatifan Dose + Midazolam; MAD-casdatifan Dose 1; MAD-casdatifan Dose 2; SAD-casdatifan Dose 1; SAD-casdatifan Dose 2; SAD-casdatifan Dose 3; SAD-casdatifan Dose 4

Placebo DRUG

Capsule

MAD-Placebo; SAD-Placebo

Midazolam DRUG

Syrup solution

DDI-casdatifan Dose + Midazolam

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Arcus Biosciences, Inc.: lead

Study Sites (1)

Investigational Site

Groningen, Netherlands

Location

Related Links

• ARC-14 - Public website

MeSH Terms

Interventions

Midazolam

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Arcus Biosciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 11, 2021
• Study Start: November 9, 2021
• Primary Completion: February 17, 2023
• Study Completion: February 17, 2023
• Last Updated: October 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR

Locations

NL (1)