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

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ClinicalTrials.gov Identifier: NCT05117554
Recruitment Status : Recruiting
First Posted : November 11, 2021
Last Update Posted : November 10, 2022
Sponsor:
Information provided by (Responsible Party):
Arcus Biosciences, Inc.

Brief Summary:
This study will evaluate the safety and tolerability, pharmacokinetic, and pharmacodynamic profile, and drug-drug interaction (DDI) of AB521 in healthy participants.

Condition or disease Intervention/treatment Phase
Healthy Participants Drug: AB521 Drug: Placebo Drug: Midazolam Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : November 1, 2021
Estimated Primary Completion Date : December 5, 2022
Estimated Study Completion Date : December 5, 2022

Arm Intervention/treatment
Experimental: SAD-AB521 Dose 1
Participants will receive "Dose 1" of AB521 orally with water under fasting conditions.
Drug: AB521
Capsule

Experimental: SAD-AB521 Dose 2
Participants will receive "Dose 2" of AB521 orally with water under fasting conditions.
Drug: AB521
Capsule

Experimental: SAD-AB521 Dose 3
Participants will receive "Dose 3" of AB521 orally with water under fasting conditions.
Drug: AB521
Capsule

Experimental: SAD-AB521 Dose 4
Participants will receive "Dose 4" of AB521 orally with water under fasting conditions.
Drug: AB521
Capsule

Placebo Comparator: SAD-Placebo
Participants will receive matching placebo orally with water under fasting conditions.
Drug: Placebo
Capsule

Experimental: MAD-AB521 Dose 1
Participants will receive "Dose 1" of AB521 orally with water under fasting conditions.
Drug: AB521
Capsule

Experimental: MAD-AB521 Dose 2
Participants will receive "Dose 2" of AB521 orally with water under fasting conditions.
Drug: AB521
Capsule

Placebo Comparator: MAD-Placebo
Participants will receive matching placebo orally with water under fasting conditions.
Drug: Placebo
Capsule

Experimental: DDI-AB521 Dose + Midazolam
Participants will receive highest safe dose level of AB521 from MAD and midazolam orally with water under fasting conditions
Drug: AB521
Capsule

Drug: Midazolam
Syrup solution




Primary Outcome Measures :
  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 AB521 [ 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 AB521 [ Time Frame: multiple timepoints up to approximately 21.5 Weeks ]
  6. Time of Occurrence of Cmax (tmax) of AB521 [ Time Frame: multiple timepoints up to approximately 21.5 Weeks ]
  7. Apparent Terminal Elimination Rate Constant (λz) of AB521 [ Time Frame: multiple timepoints up to approximately 21.5 Weeks ]
  8. Terminal Half-Life (t1/2) of AB521 [ 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 AB521 [ Time Frame: multiple timepoints up to approximately 21.5 Weeks ]
  10. Apparent Volume of Distribution of AB521 [ Time Frame: multiple timepoints up to approximately 21.5 Weeks ]
  11. Apparent Total Body Clearance of AB521 [ Time Frame: multiple timepoints up to approximately 21.5 Weeks ]

Secondary Outcome Measures :
  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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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:

    1. SAD: male and female hemoglobin level ≥ 12.5 grams/ deciliters (g/dL) (7.7 millimoles/liters [mmol/L])
    2. 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05117554


Contacts
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Contact: Medical Director +1-510-462-3330 ClinicalTrialInquiry@arcusbio.com

Locations
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Netherlands
Investigational Site Recruiting
Groningen, Netherlands
Sponsors and Collaborators
Arcus Biosciences, Inc.
Investigators
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Study Director: Medical Director Arcus Biosciences, Inc.
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Responsible Party: Arcus Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT05117554    
Other Study ID Numbers: ARC-14
2021-003856-17 ( EudraCT Number )
First Posted: November 11, 2021    Key Record Dates
Last Update Posted: November 10, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Arcus will provide access to individual de-identified participant data and related study documents (e.g., protocol, Statistical Analysis Plan [SAP], Clinical Study Report [CSR]) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Arcus Biosciences, Inc.:
AB521
HIF-2α
hypoxia-inducible factor 2 alpha
Single ascending dose (SAD)
Multiple ascending dose (MAD)
Drug-drug interaction (DDI)
Additional relevant MeSH terms:
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Midazolam
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action