Study to Investigate the Safety, Tolerability, and Pharmacokinetic Profile With Oral AB521 in Healthy Volunteers (ARC-14)

Arcus Biosciences

Status and phase: Completed; Phase 1

Conditions: Healthy Participants

Treatments: Drug: Placebo; Drug: casdatifan; Drug: Midazolam

Study type: Interventional

Funder types: Industry

Identifiers

NCT05117554

2021-003856-17 (EudraCT Number)

ARC-14

Details and patient eligibility

About

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

Enrollment: 70 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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70 participants in 9 patient groups, including a placebo group

SAD-casdatifan Dose 1

Experimental group

Description:

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

Treatment:

Drug: casdatifan

SAD-casdatifan Dose 2

Experimental group

Description:

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

Treatment:

Drug: casdatifan

SAD-casdatifan Dose 3

Experimental group

Description:

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

Treatment:

Drug: casdatifan

SAD-casdatifan Dose 4

Experimental group

Description:

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

Treatment:

Drug: casdatifan

SAD-Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

MAD-casdatifan Dose 1

Experimental group

Description:

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

Treatment:

Drug: casdatifan

MAD-casdatifan Dose 2

Experimental group

Description:

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

Treatment:

Drug: casdatifan

MAD-Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

DDI-casdatifan Dose + Midazolam

Experimental group

Description:

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

Treatment:

Drug: Midazolam

Drug: casdatifan