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.
- Conditions
- Renal cell carcinomacancer
- Registration Number
- NL-OMON51736
- Lead Sponsor
- Arcus Biosciences, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 68
1. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in
this protocol.
2. Participant must be at least 18 to 55 years of age inclusive, at the time of
signing the informed consent.
3. 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 ECG.
4. Participants must have clinical laboratory tests within the reference range
for age and gender at screening and baseline.
5. Screening and randomization hemoglobin for males and females is as follows:
a) SAD: male and female hemoglobin level >= 12.5 g/dL (7.7 mmol/L)
b) 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).
Further criteria apply
1. Has any (acute or chronic [including 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.
2. 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 IMP; constituting a risk when taking
the study intervention; or interfering with the interpretation of data in the
opinion of the investigator.
3. 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 mm Hg or mean diastolic BP >= 89 mm Hg; mean pulse < 40
bpm or > 100 bpm. Study participants with a BP within normal range but who, in
the opinion of the investigator, have a high risk for cardiovascular accident
based on, eg, family history, smoking, BMI, or lipid spectrum can be excluded.
Results that are outside the specified ranges and are deemed clinically
non-significant will be allowed at the discretion of the investigator, after
discussion with the Sponsor Medical Monitor (or designee). If a study
participant has a test result outside the normal range that is deemed
potentially clinically significant, repeat of the investigation may be allowed
once at the discretion of the investigator, after discussion with the Sponsor
Medical Monitor (or designee).
4. The following liver enzyme test results:
a) Alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin,
or alkaline phosphatase (ALP) >1.0× upper limit of normal (ULN).
• Tests that result in ALT, AST, bilirubin, or ALP up to 25% above the
exclusion limit may be repeated once for confirmation.
b) Current or chronic history of liver disease or known hepatic or biliary
abnormalities (with the exception of asymptomatic gallstones).
5. Has 12-lead ECG with changes considered to be clinically significant (eg,
QTcF > 450 msec for males and > 470 msec for females, left bundle branch block,
or evidence of myocardial ischemia) at the Screening Visit or Day -2/-1
(Admission).
Further criteria apply
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- To assess the safety and tolerability of AB521 after single- and multiple<br /><br>oral doses.<br /><br><br /><br>- To characterize the PK profile of AB521 after single- and multiple oral<br /><br>doses.</p><br>
- Secondary Outcome Measures
Name Time Method <p>- To evaluate the effect of multiple oral doses of AB521 on the PK of midazolam<br /><br>when midazolam is administered as a single dose<br /><br><br /><br>Exploratory:<br /><br>- To assess the potential PD effects of AB521<br /><br>- To characterize AB521 excretion in urine<br /><br>- To characterize potential metabolite(s) of AB521 in plasma and urine</p><br>