Healthy ParticipantsPhase 1ARC-14NCT05117554

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

A Phase 1 study testing casdatifan and Midazolam in people with Healthy Participants, run by Arcus Biosciences, Inc. at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Participants
What is being tested?: casdatifan and Midazolam
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 70 participants
Where: 1 siteNetherlands
Study dates: 9 Nov 2021to 17 Feb 2023
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

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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

Who cannot join

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 locations and contacts

1 site in 1 country.

Netherlands1 site

Investigational Site
Groningen

Other trials in Netherlands

About this study

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

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
Being tested: casdatifan, Placebo, Midazolam
Keywords: AB521, HIF-2α, hypoxia-inducible factor 2 alpha, Single ascending dose (SAD), Multiple ascending dose (MAD), Drug-drug interaction (DDI), casdatifan

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

casdatifanDrug
Also called AB521
Capsule
PlaceboDrug
Capsule
MidazolamDrug
Syrup solution

Study groups in NCT05117554
Study group	Role	What they receive
SAD-casdatifan Dose 1	Experimental	Participants will receive "Dose 1" of casdatifan orally with water under fasting conditions. Receives: Drug: casdatifan
SAD-casdatifan Dose 2	Experimental	Participants will receive "Dose 2" of casdatifan orally with water under fasting conditions. Receives: Drug: casdatifan
SAD-casdatifan Dose 3	Experimental	Participants will receive "Dose 3" of casdatifan orally with water under fasting conditions. Receives: Drug: casdatifan
SAD-casdatifan Dose 4	Experimental	Participants will receive "Dose 4" of casdatifan orally with water under fasting conditions. Receives: Drug: casdatifan
SAD-Placebo	Placebo comparator	Participants will receive matching placebo orally with water under fasting conditions. Receives: Drug: Placebo
MAD-casdatifan Dose 1	Experimental	Participants will receive "Dose 1" of casdatifan orally with water under fasting conditions. Receives: Drug: casdatifan
MAD-casdatifan Dose 2	Experimental	Participants will receive "Dose 2" of casdatifan orally with water under fasting conditions. Receives: Drug: casdatifan
MAD-Placebo	Placebo comparator	Participants will receive matching placebo orally with water under fasting conditions. Receives: 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 Receives: Drug: casdatifan; Drug: Midazolam

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Measured: Up to 21.5 Weeks
Number of Participants With Abnormal Changes From Baseline in Laboratory Parameter Values
Measured: Baseline; Up to 21.5 Weeks
Number of Participants With Abnormal Changes from Baseline in Vital Sign Values
Measured: Baseline; Up to 21.5 Weeks
Maximum Observed Plasma Concentration (Cmax) of casdatifan
Measured: 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
Measured: multiple timepoints up to approximately 21.5 Weeks
Time of Occurrence of Cmax (tmax) of casdatifan
Measured: multiple timepoints up to approximately 21.5 Weeks
Apparent Terminal Elimination Rate Constant (λz) of casdatifan
Measured: multiple timepoints up to approximately 21.5 Weeks
Terminal Half-Life (t1/2) of casdatifan
Measured: multiple timepoints up to approximately 21.5 Weeks
Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUCinf) of casdatifan
Measured: multiple timepoints up to approximately 21.5 Weeks
Apparent Volume of Distribution of casdatifan
Measured: multiple timepoints up to approximately 21.5 Weeks
Apparent Total Body Clearance of casdatifan
Measured: multiple timepoints up to approximately 21.5 Weeks

Secondary outcomes (8)

Maximum Observed Plasma Concentration (Cmax) of midazolam and 1 hydroxymidazolam
Measured: 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
Measured: multiple timepoints up to approximately 21.5 Weeks
Time of Occurrence of Cmax (tmax) of midazolam and 1 hydroxymidazolam
Measured: multiple timepoints up to approximately 21.5 Weeks
Apparent Terminal Elimination Rate Constant (λz) of midazolam and 1 hydroxymidazolam
Measured: multiple timepoints up to approximately 21.5 Weeks
Terminal Half-Life (t1/2) of midazolam and 1 hydroxymidazolam
Measured: 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
Measured: multiple timepoints up to approximately 21.5 Weeks
Apparent Volume of Distribution of midazolam and 1 hydroxymidazolam
Measured: multiple timepoints up to approximately 21.5 Weeks
Apparent Total Body Clearance of midazolam and 1 hydroxymidazolam
Measured: multiple timepoints up to approximately 21.5 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Nov 202117 Feb 2023

First posted11 Nov 2021
Study start9 Nov 2021
Primary completion17 Feb 2023
Study completion17 Feb 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Healthy ParticipantsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 70 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05117554
Sponsor's protocol ID: ARC-14
Other IDs: 2021-003856-17
Acronym: ARC-14
Status last verified: May 2024
First submitted: 2 Nov 2021
Last updated: 17 Oct 2024
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: 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. For more information, please visit our website.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 17 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05117554
Acronym / sponsor ID: ARC-14 / ARC-14
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
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 70 participants (actual)
Lead sponsor: Arcus Biosciences, Inc.Industry (pharma, biotech, devices)
Study start: 9 Nov 2021 (actual)
Primary completion: 17 Feb 2023 (actual)
Study completion: 17 Feb 2023 (actual)
First posted: 11 Nov 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 9

Arm	Type	Receives
SAD-casdatifan Dose 1	Experimental	Drug: casdatifanParticipants will receive "Dose 1" of casdatifan orally with water under fasting conditions.
SAD-casdatifan Dose 2	Experimental	Drug: casdatifanParticipants will receive "Dose 2" of casdatifan orally with water under fasting conditions.
SAD-casdatifan Dose 3	Experimental	Drug: casdatifanParticipants will receive "Dose 3" of casdatifan orally with water under fasting conditions.
SAD-casdatifan Dose 4	Experimental	Drug: casdatifanParticipants will receive "Dose 4" of casdatifan orally with water under fasting conditions.
SAD-Placebo	Placebo comparator	Drug: PlaceboParticipants will receive matching placebo orally with water under fasting conditions.
MAD-casdatifan Dose 1	Experimental	Drug: casdatifanParticipants will receive "Dose 1" of casdatifan orally with water under fasting conditions.
MAD-casdatifan Dose 2	Experimental	Drug: casdatifanParticipants will receive "Dose 2" of casdatifan orally with water under fasting conditions.
MAD-Placebo	Placebo comparator	Drug: PlaceboParticipants will receive matching placebo orally with water under fasting conditions.
DDI-casdatifan Dose + Midazolam	Experimental	Drug: casdatifan, Drug: MidazolamParticipants will receive highest safe dose level of casdatifan from MAD and midazolam orally with water under fasting conditions

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (9 listed)

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:
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)

Key exclusion criteria (6 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
casdatifanAlso: AB521Capsule	Drug	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
PlaceboCapsule	Drug	MAD-Placebo, SAD-Placebo
MidazolamSyrup solution	Drug	DDI-casdatifan Dose + Midazolam

Primary outcome

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to 21.5 Weeks
Number of Participants With Abnormal Changes From Baseline in Laboratory Parameter Values
Time frame: Baseline; Up to 21.5 Weeks
Number of Participants With Abnormal Changes from Baseline in Vital Sign Values
Time frame: Baseline; Up to 21.5 Weeks
Maximum Observed Plasma Concentration (Cmax) of casdatifan
Time frame: 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
Time frame: multiple timepoints up to approximately 21.5 Weeks
Time of Occurrence of Cmax (tmax) of casdatifan
Time frame: multiple timepoints up to approximately 21.5 Weeks
Apparent Terminal Elimination Rate Constant (λz) of casdatifan
Time frame: multiple timepoints up to approximately 21.5 Weeks
Terminal Half-Life (t1/2) of casdatifan
Time frame: multiple timepoints up to approximately 21.5 Weeks
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
Apparent Volume of Distribution of casdatifan
Time frame: multiple timepoints up to approximately 21.5 Weeks
Apparent Total Body Clearance of casdatifan
Time frame: multiple timepoints up to approximately 21.5 Weeks

8 secondary outcomes

Maximum Observed Plasma Concentration (Cmax) of midazolam and 1 hydroxymidazolam
Time frame: 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
Time frame: multiple timepoints up to approximately 21.5 Weeks
Time of Occurrence of Cmax (tmax) of midazolam and 1 hydroxymidazolam
Time frame: multiple timepoints up to approximately 21.5 Weeks
Apparent Terminal Elimination Rate Constant (λz) of midazolam and 1 hydroxymidazolam
Time frame: multiple timepoints up to approximately 21.5 Weeks
Terminal Half-Life (t1/2) of midazolam and 1 hydroxymidazolam
Time frame: 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
Time frame: multiple timepoints up to approximately 21.5 Weeks
Apparent Volume of Distribution of midazolam and 1 hydroxymidazolam
Time frame: multiple timepoints up to approximately 21.5 Weeks
Apparent Total Body Clearance of midazolam and 1 hydroxymidazolam
Time frame: multiple timepoints up to approximately 21.5 Weeks

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2024.
ARC-14 - Public websiteLink provided by the sponsor.
Individual participant dataSharing planned: Yes. 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. For more information, please visit our website.

Related trials for Healthy Participants

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Arcus Biosciences, Inc.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing casdatifan and Midazolam in people with Healthy Participants, run by Arcus Biosciences, Inc. at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: Up to 21.5 Weeks). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05117554.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Oct 2024.