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

Phase 1

Completed

• Conditions: Healthy Participants
• Interventions: Drug: casdatifan; Drug: Placebo; Drug: Midazolam

• Registration Number: NCT05117554
• Lead Sponsor: Arcus Biosciences, Inc.

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-11-02
• Study First Submitted QC: 2021-11-02
• Study Start: 2021-11-09
• Study First Posted: 2021-11-11
• Primary Completion: 2023-02-17
• Study Completion: 2023-02-17
• Status Verified: 2024-05
• Last Update Submitted: 2024-10-16
• Last Update Posted: 2024-10-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SAD-casdatifan Dose 1	casdatifan	Participants will receive "Dose 1" of casdatifan orally with water under fasting conditions.
SAD-casdatifan Dose 2	casdatifan	Participants will receive "Dose 2" of casdatifan orally with water under fasting conditions.
SAD-casdatifan Dose 3	casdatifan	Participants will receive "Dose 3" of casdatifan orally with water under fasting conditions.
SAD-casdatifan Dose 4	casdatifan	Participants will receive "Dose 4" of casdatifan orally with water under fasting conditions.
SAD-Placebo	Placebo	Participants will receive matching placebo orally with water under fasting conditions.
MAD-casdatifan Dose 1	casdatifan	Participants will receive "Dose 1" of casdatifan orally with water under fasting conditions.
MAD-casdatifan Dose 2	casdatifan	Participants will receive "Dose 2" of casdatifan orally with water under fasting conditions.
MAD-Placebo	Placebo	Participants will receive matching placebo orally with water under fasting conditions.
DDI-casdatifan Dose + Midazolam	casdatifan	Participants will receive highest safe dose level of casdatifan from MAD and midazolam orally with water under fasting conditions
DDI-casdatifan Dose + Midazolam	Midazolam	Participants will receive highest safe dose level of casdatifan from MAD and midazolam orally with water under fasting conditions

Primary Outcome Measures

Name	Time	Method
Apparent Total Body Clearance 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
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

Secondary Outcome Measures

Name	Time	Method
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
Terminal Half-Life (t1/2) 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
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
Apparent Volume of Distribution of midazolam and 1 hydroxymidazolam	multiple timepoints up to approximately 21.5 Weeks
Apparent Total Body Clearance of midazolam and 1 hydroxymidazolam	multiple timepoints up to approximately 21.5 Weeks

Trial Locations

Locations (1)

Investigational Site; 🇳🇱 Groningen, Netherlands