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Completed

NCT Number: NCT05117554

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

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

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Key information

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Investigational Site

Groningen, Netherlands

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

casdatifan

Drug

Capsule

Other names: AB521

Placebo

Drug

Capsule

midazolam

Drug

Syrup solution

Primary outcomes

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

    Time frame: Up to 21.5 Weeks

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

    Time frame: Baseline; Up to 21.5 Weeks

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

    Time frame: Baseline; Up to 21.5 Weeks

  4. Maximum Observed Plasma Concentration (Cmax) of casdatifan

    Time frame: multiple timepoints up to approximately 21.5 Weeks

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

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  6. Time of Occurrence of Cmax (tmax) of casdatifan

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  7. Apparent Terminal Elimination Rate Constant (λz) of casdatifan

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  8. Terminal Half-Life (t1/2) of casdatifan

    Time frame: multiple timepoints up to approximately 21.5 Weeks

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

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  10. Apparent Volume of Distribution of casdatifan

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  11. Apparent Total Body Clearance of casdatifan

    Time frame: multiple timepoints up to approximately 21.5 Weeks

Secondary outcomes

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

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  2. Area Under the Plasma Concentration Time Curve From Hour 0 to the Last Sample With Measurable Plasma Concentrations (AUClast) of midazolam and 1 hydroxymidazolam

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  3. Time of Occurrence of Cmax (tmax) of midazolam and 1 hydroxymidazolam

    Time frame: multiple timepoints up to approximately 21.5 Weeks

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

    Time frame: multiple timepoints up to approximately 21.5 Weeks

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

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  6. Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUCinf) of midazolam and 1 hydroxymidazolam

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  7. Apparent Volume of Distribution of midazolam and 1 hydroxymidazolam

    Time frame: multiple timepoints up to approximately 21.5 Weeks

  8. Apparent Total Body Clearance of midazolam and 1 hydroxymidazolam

    Time frame: multiple timepoints up to approximately 21.5 Weeks

Sponsors and collaborators

Lead sponsor

Arcus Biosciences, Inc.

Industry

Registry information

Official study 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

Acronym: ARC-14

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Nov 11, 2021
Registry last updated
Oct 17, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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