Clinical trial NCT05117554: Study to Investigate the Safety, Tolerability, and Pharmacokinetic Profile With Oral AB521 in Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
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
Lead sponsor: Arcus Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2021-11-11
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility 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:

  * 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to 21.5 Weeks
measure: Number of Participants With Abnormal Changes From Baseline in Laboratory Parameter Values
timeFrame: Baseline; Up to 21.5 Weeks
measure: Number of Participants With Abnormal Changes from Baseline in Vital Sign Values
timeFrame: Baseline; Up to 21.5 Weeks
measure: Maximum Observed Plasma Concentration (Cmax) of casdatifan
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Area Under the Plasma Concentration Time Curve From Hour 0 to the Last Sample With Measurable Plasma Concentrations (AUClast) of casdatifan
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Time of Occurrence of Cmax (tmax) of casdatifan
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Apparent Terminal Elimination Rate Constant (λz) of casdatifan
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Terminal Half-Life (t1/2) of casdatifan
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUCinf) of casdatifan
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Apparent Volume of Distribution of casdatifan
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Apparent Total Body Clearance of casdatifan
timeFrame: multiple timepoints up to approximately 21.5 Weeks
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of midazolam and 1 hydroxymidazolam
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Area Under the Plasma Concentration Time Curve From Hour 0 to the Last Sample With Measurable Plasma Concentrations (AUClast) of midazolam and 1 hydroxymidazolam
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Time of Occurrence of Cmax (tmax) of midazolam and 1 hydroxymidazolam
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Apparent Terminal Elimination Rate Constant (λz) of midazolam and 1 hydroxymidazolam
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Terminal Half-Life (t1/2) of midazolam and 1 hydroxymidazolam
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Area Under the Plasma Concentration Time Curve From Hour 0 to Infinity (AUCinf) of midazolam and 1 hydroxymidazolam
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Apparent Volume of Distribution of midazolam and 1 hydroxymidazolam
timeFrame: multiple timepoints up to approximately 21.5 Weeks
measure: Apparent Total Body Clearance of midazolam and 1 hydroxymidazolam
timeFrame: multiple timepoints up to approximately 21.5 Weeks
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: Investigational Site
Study officials:
affiliation: Arcus Biosciences, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: