| Eligibility |
Inclusion Criteria:
- Males of any race, between 18 and 55 years of age, inclusive.
- The subject has a body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive, and a
total body weight between 50 and 110 kg, inclusive.
- In good health, determined by no clinically significant findings from medical history,
physical examination (at both screening and check-in), vital sign measurements,
12-lead electrocardiogram (ECG), and clinical laboratory evaluations (at both
screening and check-in) as assessed by the Investigator (or designee).
- The subject is able to speak, read, and understand English and is willing to provide
written informed consent.
- The subject is a non-smoker for the past 6 months.
- Must agree to use contraception History of a minimum of 1 bowel movement per day.
- The subject is willing and able to comply with all testing and requirements defined in
the protocol.
- The subject must have completed a coronavirus disease (COVID-19) vaccine primary
series ("fully vaccinate") at least 4 weeks prior to inpatient treatment day 1 of the
study OR have COVID-19 virus serology consistent with prior vaccination or exposure.
Exclusion Criteria:
- The subject has had a clinically significant illness within 30 days prior to the
Screening Visit.
- The subject has a significant history or clinical manifestation of any allergic,
cardiovascular, dermatological, endocrine, gastrointestinal, hepatic, metabolic,
neurological, psychiatric, pulmonary, renal, respiratory, or psychiatric disorder, as
determined by the Investigator (or designee).
- The subject has a history of significant hypersensitivity, intolerance, or allergy to
any drug compound, food, or other substance, unless approved by the Investigator (or
designee).
- History of stomach or intestinal surgery or resection that would potentially alter
absorption and/or excretion of orally administered drugs (uncomplicated appendectomy
and hernia repair will be allowed). A history of a cholecystectomy is exclusionary.
- Confirmed (e.g., 2 consecutive measurements) systolic blood pressure > 140 or < 90
mmHg, diastolic blood pressure > 90 or < 50 mmHg, and pulse rate > 100 or < 40 beats
per minute. Minor deviations from the normal range may be allowed if deemed by the
Investigator (or designee) to have no clinical significance.
- The subject has a clinically significant electrocardiogram (ECG) abnormality as
evaluated by the Investigator (or designee).
- The subject has a clinically significant medical or laboratory abnormality or disease
that, in the opinion of the investigator, should exclude the subject from the study,
including:
- a. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST), or alkaline
phosphatase (ALP) outside of the normal range at screening.
- Evidence of renal impairment (GFR < 90 mL/min/1.73m2 using the National Kidney
Foundation CKD-EPI 2021 Creatinine Equation [9].
- Presence of congenital nonhemolytic hyperbilirubinemia (i.e., Gilbert's syndrome based
on an assessment of total and direct bilirubin).
- The subject has a positive serum hepatitis B surface antigen test at the Screening
Visit.
- The subject has or has had hepatitis C, as confirmed by a positive hepatitis C virus
(HCV) antibody test at the Screening Visit.
- The subject has a positive human immunodeficiency virus (HIV) test at the Screening
Visit
- The subject has been administered any vaccine in the 14-day period prior to dosing.
- The subject has used or intends to use any medications/products known to alter drug
absorption, metabolism, or elimination processes, including St. John's wort, within 28
days prior to dosing, unless deemed acceptable by the Investigator (or designee) and
Medical Monitor, in consultation with the Sponsor.
- The subject has used or intends to use any prescription medication within 14 days of
dosing or over the counter (OTC) medications/products including vitamins, minerals,
and phytotherapeutic/herbal/plant-derived preparations within 48 hours of dosing and
during the study unless deemed acceptable by both the Investigator (or designee) and
Medical Monitor, in consultation with the Sponsor.
- The subject has used or intends to use slow-release medications/products considered to
still be active within 14 days prior to check-in, unless deemed acceptable by the
Investigator (or designee).
- The subject has received an investigational drug within 30 days prior to the Screening
Visit.
- The subject has previously received simufilam.
- The subject has participated in = 3 radiolabeled drug studies in the last 12 months
(with most recent study to be at least 4 months prior to check-in to the study site
where exposures are known to the investigator or 6 months prior to check-in to the
study site for a radiolabeled drug study where exposures are not known to the
investigator). The total 12-month exposure from this study and a maximum of 2 other
previous radiolabeled studies within 4 to 12 months prior to this study will be within
the Code of Federal Regulations (CFR) recommended levels considered safe, per United
States (US) Title 21 CFR 361.1.
- The subject has a history of substance abuse within 12 months of the Screening Visit
or a current positive alcohol urine test or urine drug screen at the Screening Visit
or at check-in.
- The subject has a history of regular alcohol consumption defined as greater than 14
drinks per week within six months prior to the Screening Visit. One drink is
equivalent to 12 g alcohol = 5 oz (150 mL) of wine or 12 oz (360 mL) of beer or 1.5 oz
(45 mL) of 80 proof distilled spirits.
- The subject has used tobacco- or nicotine-containing products within 6 months prior to
dosing or has a positive cotinine test at the Screening Visit or at check-in.
- The subject has consumed alcohol, caffeine, grapefruit, grapefruit juice, or
xanthine-containing products within 72 hours before dosing or intends to use any of
these products during the study.
- The subject has received blood products within 2 months prior to check-in.
- The subject has donated or lost a significant volume of blood (>500 mL) within a 90-
day period prior to the Screening Visit or has donated plasma less than 2 weeks or
platelets less than 6 weeks prior to the Screening Visit.
- The subject is unwilling to reside in the study unit for the duration of the study or
unwilling to cooperate fully with the Investigator or site personnel.
- Subjects with poor peripheral venous access.
- Subjects with exposure to significant diagnostic or therapeutic radiation (e.g.,
serial x-ray, computed tomography scan, barium meal) or current employment in a job
requiring radiation exposure monitoring within 12 months prior to check-in.
- Subjects who, in the opinion of the Investigator (or designee), should not participate
in this study.
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