| Eligibility |
Inclusion Criteria:
- Healthy as determined by the Investigator, based on a medical evaluation including
medical history physical examination, neurological examination, laboratory tests and
cardiac monitoring. A subject with a clinical abnormality or laboratory parameters
outside the reference range for the population being studied may be included only if,
in the opinion of the Investigator, the finding is (a) unlikely to introduce
additional risk to the subject, (b) will not interfere with study procedures or
confound study results, and (c) is not otherwise exclusionary
- Men or women aged 25-55 years, inclusive (age range was selected on grounds of
radiation burden).
- Women of child-bearing potential (WOCBP) with partners of child-bearing potential must
agree to use highly effective contraception from at least 28 days before first tracer
dosing through 30 days after last dose of study medication. All WOCBP must have a
negative pregnancy test result before administration of test article. Vasectomized
partner is also an accepted a highly effective birth control method provided that
partner is the sole sexual partner of the WOCBP trial participant and that the
vasectomized partner has received medical assessment of the surgical success.
- WOCBP must be postmenopausal (the last menstrual period was at least 12 months ago,
and follicle-stimulating hormone at screening confirms postmenopausal status, or have
no uterus, ovaries, or fallopian tubes). Women who are surgically sterile must provide
documentation of the procedure by an operative report or by ultrasound.
- Non-sterilized male subjects who are not abstinent and intend to be sexually active
with a female partner of childbearing potential must use a male condom plus spermicide
from 1 day prior to the first tracer administration throughout the total duration of
the treatment period and 90 days after the last dose of study drug. Periodic
abstinence, the rhythm method, and the withdrawal method are not acceptable methods of
contraception. Male subjects should refrain from sperm donation throughout this
period.
- Body weight > 50.0 kg for men and > 45.0 kg for women and Body Mass Index within the
range 18.5-30.0 kg/m2 (inclusive).
- Subjects must understand the nature of the study and must provide signed and dated
written informed consent in accordance with local regulations before the conduct of
any study-related procedures.
- Subjects must be, in the opinion of the Investigator, able to participate in all
scheduled evaluations, likely to complete all required tests, and likely to be
compliant.
- Subjects must be fluent in the local language.
- Subjects must agree not to post any personal medical data related to the study or
information related to the study on any website or social media site (e.g., Facebook,
Twitter, etc.) until the trial has completed.
Exclusion Criteria:
- A positive urine drug screen/alcohol test at Screening or Day -1.
- Any history of psychiatric disorders, including substance use disorders, according to
the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5)
criteria.
- A diagnosis of intellectual disability (intellectual developmental disorder) or mental
retardation.
- Significant suicide risk as assessed by the Columbia Suicide severity Rating Scale
(C-SSRS)
- A positive Hepatitis B surface antigen or positive Hepatitis C antibody result at
Screening.
- A positive test for human immunodeficiency virus (HIV) antibody at Screening.
- Alanine aminotransferase or aspartate aminotransferase levels greater than 1.5 times
the upper limit of normal (ULN) at Screening or between Screening and first dose of
tracer.
- Frequently used any tobacco-containing (e.g., cigar, cigarette, or snuff) or
nicotine-containing product (e.g., nicotine chewing gum, nicotine plasters, or other
product used for smoking cessation) within 3 months prior to first dose of tracer.
Frequent use is defined as 3 or more days per week. Use of any tobacco- or
nicotine-containing product is prohibited within 1 week of first dose of tracer.
- History of regular alcohol consumption within 12 months of the study defined as an
average weekly intake of >21 alcoholic units/week for men or >14 alcoholic units/week
for women.
- Regularly consumed (e.g., more days than not) excessive quantities of
xanthine-containing beverages (e.g., more than five cups of coffee or the equivalent
per day) within 30 days prior to Screening or between Screening and first dose of
tracer.
- Received or used an investigational product (including placebo) or device within the
following time period prior to the first tracer dosing day in the current study: 90
days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).
- Use of prescription or non-prescription drugs, vitamins, herbal, and dietary
supplements (including St John's Wort) within 7 days (or 28 days if the drug is a
potential hepatic enzyme inducer) or 5 half-lives (whichever is longer) prior to the
first dose of study tracer medication, unless in the opinion of the Investigator and
Medical Monitor, the medication will not interfere with the study procedures or
compromise subject safety.
- History of clinically significant sensitivity to any of the study medications, or
components thereof or a history of drug or other allergy that, in the opinion of the
Investigator or Medical Monitor, contraindicates their participation.
- Loss of more than 400 mL of blood within 3 months prior to first dose of tracer, i.e.,
blood donor.
- A positive serum pregnancy test or lactation.
- A history or presence of any disease, condition, or surgery likely to affect drug
absorption, distribution, metabolism, or excretion. Subjects with a history of
cholecystectomy should be excluded.
- A history or presence of a clinically significant hepatic, renal, gastrointestinal,
cardiovascular, endocrine, pulmonary, ophthalmologic, immunologic, hematologic,
dermatologic, or neurologic abnormality.
- A clinically significant abnormality on physical examination, neurological
examination, electrocardiogram (ECG), or laboratory evaluations at screen or between
screen and first tracer dose administration.
- A corrected QT(total time from ventricular depolarization to complete repolarization)
interval measurement corrected according to the Fridericia rule (QTcF) > 450 msec for
males and 470 msec for females during controlled rest at screen or between screen and
first tracer dose administration, or family history of long QT syndrome.
- Any clinically significant abnormalities in rhythm, conduction, or morphology of the
resting ECG and any abnormalities in the 12-lead ECG that, in the judgement of the
Investigator or Medical Monitor, may interfere with the interpretation of QTc interval
changes, including abnormal ST-T-wave morphology or left ventricular hypertrophy.
- PR (PQ) interval shortening < 120 msec (PR < 120 msec but > 110 msec is acceptable if
there is no evidence of ventricular pre-excitation).
- PR (PQ) interval prolongation (>220 msec), intermittent second- (Wenckebach block
while asleep or in deep rest is not exclusionary) or third-degree AV block.
- Persistent or intermittent complete bundle branch block (BBB), incomplete bundle
branch block (IBBB), or intraventricular conduction delay (IVCD) with QRS > 120 msec.
- A clinically significant vital signs abnormality at screening This includes, but is
not limited to, 3 measurements (each 5 minutes apart) in the seated position: (a)
systolic blood pressure < 90 or >140 mmHg, (b) diastolic blood pressure <50 or > 95
mmHg, or (c) heart rate < 45 or >100 beats per minute. The average of the 3
measurements should be used to assess eligibility at screening.
- Significant (> 10%) weight loss or gain within 30 days prior to Screening and first
tracer dose administration.
- A history of seizure. History of a single benign febrile convulsion of childhood is
permitted.
- A history of head trauma, including closed head injury with loss of consciousness.
- A history of symptomatic orthostatic hypotension (i.e., postural syncope).
- A history of neuroleptic malignant syndrome.
- A history of chronic urinary tract infections.
- The subject is, in the opinion of the Investigator or Medical Monitor, unlikely to
comply with the protocol or is unsuitable for any reason.
- Currently employed by Asceneuron SA or by a clinical trial site participating in this
study, or a first-degree relative of an Asceneuron SA employee or of an employee at a
participating clinical trial site.
- Unsatisfactory venous access
- Significant exposure to ionizing radiation as part of research within the previous 12
months prior to first tracer dose administration.
- Unsuitable or unwilling to undergo the imaging procedures, as determined by an
magnetic resonance imaging (MRI) safety questionnaire. Reasons for exclusion include
but are not limited to presence of a cardiac pacemaker or other implanted electronic
device; ferromagnetic metal foreign bodies, intracranial aneurysm clips or other
metallic objects; non-MRI compatible heart valves; inner ear implants; or a history of
claustrophobia.
- Significant structural brain abnormality, as determined by MRI.
- Contraindication for arterial cannulation: Allen's test indicating potential risk in
placement of the arterial cannula.
- Subjects with a COVID-19 vaccination within two weeks of screening or due to receive
second dose of COVID-19 vaccine while participating in the study.
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