| Eligibility |
Inclusion Criteria:
1. Male subjects, ages 18 to 55 years, inclusive, at the time of signing the informed
consent form (ICF).
2. Body mass index (BMI) of 18.0 to 32.0 kg/m2 and a total body weight > 50 kg (110 lbs).
3. In good health, determined by no clinically significant findings from medical history,
physical examination, 12-lead electrocardiogram (ECG), vital signs measurements, and
clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg,
Gilbert's syndrome] is not acceptable) at Screening or Check-in as assessed by the
investigator (or designee).
4. Male subjects with a pregnant or a nonpregnant partner of childbearing potential must
agree to use an acceptable or a highly effective method of contraception from signing
of informed consent during the trial, and for 7 days following the last dose of study
drug.
5. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the ICF and in the protocol.
6. Ability, in the opinion of the investigator, to understand the nature of the trial and
comply with protocol requirements, including the prescribed dosage regimens, scheduled
visits, laboratory tests, and other trial procedures.
7. Capable of consuming the standard diet.
8. History of a minimum of 1 bowel movement per day.
Exclusion Criteria:
- Medical History and Concurrent Diseases
1. Has a history of psychotic symptoms requiring treatment with an antipsychotic
medication within the 12 months prior to signing ICF.
2. Subjects with epilepsy, or history of epilepsy, or conditions that lower seizure
threshold, seizures of any etiology (including substance or drug withdrawal), or who
have increased risk of seizures as evidenced by history of electroencephalogram with
epileptiform activity. Subjects with a history of febrile seizures and/or history of
head trauma with loss of consciousness requiring hospitalization overnight will be
excluded as well.
3. Subjects with a current history of significant cardiovascular, pulmonary,
gastrointestinal, renal, hepatic, metabolic, hematological, immunological, or
neurological disease that, in the opinion of the investigator or medical monitor,
could compromise either subject safety or the results of the trial.
Medical conditions that are minor or well controlled may be considered acceptable if
the condition does not expose the subject to an undue risk of a significant AE or
interfere with the assessments of safety during the course of the trial. The medical
monitor should be contacted in any instance where the investigator is uncertain
regarding the stability of a subject's medical conditions(s) and the potential impact
of the condition(s) on trial participation.
4. Any condition possibly affecting drug absorption including 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; cholecystectomy and bariatric weight loss surgeries will not be
allowed).
5. History of substance or alcohol-use disorder (excluding nicotine; Diagnostic and
Statistical Manual of Mental Disorders, 5th edition criteria) within 2 years prior to
signing the ICF.
6. History of regular alcohol consumption exceeding 14 drinks/week [1 drink = 5 ounces
(150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor]
within 6 months prior to signing ICF.
7. Use of tobacco- or nicotine-containing products within 3 months prior to Check-in.
8. Subjects who answer "yes" on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Suicidal Ideation Item 4 or Item 5 (Active Suicidal Ideation with Some Intent to Act,
Without Specific Plan, or Active Suicidal Ideation with Specific Plan and Intent) and
whose most recent episode meeting the criteria for C-SSRS Item 4 or Item 5 occurred
within the last 6 months, OR
Subjects who answer "yes" on any of the 5 C-SSRS Suicidal Behavior Items (actual
attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and
whose most recent episode meeting the criteria for any of these 5 C-SSRS Suicidal
Behavior Items occurred within the last 2 years, OR
Subjects who, in the opinion of the investigator, present a serious risk of suicide.
9. Subjects who have attempted suicide in the past.
- Physical Examination and Clinical Laboratory Results
10. Positive hepatitis panel (hepatitis B surface antigen and hepatitis C virus antibody)
and/or positive human immunodeficiency virus test (HIV-1 and HIV-2 antibody) at
Screening.
11. Positive urine drug screen (with cotinine) or positive alcohol breathalyzer at
Screening and Check-in. Subjects with a positive drug screen for illicit drugs or
cotinine are excluded and may not be retested or rescreened. Subjects with a positive
urine drug screen resulting from use of marijuana (any cannabinoids), prescription
medications, over-the-counter medications, or products that, in the investigator's
documented opinion, do not signal a clinical condition that would impact the safety of
the subject or interpretation of the trial results may continue evaluation for the
trial following consultation and explicit approval by the medical monitor.
12. Subjects with a 12-lead ECG demonstrating the following:
• QT interval corrected for heart rate using Fridericia's formula >450 msec (average
of 3 ECGs obtained at the Screening Visit).
13. Subjects with any of the following abnormalities in clinical laboratory tests at the
Screening Visit, confirmed by a single repeat measurement, if deemed necessary, and at
the discretion of the investigator:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =2 × upper
limit of normal (ULN)
- Total bilirubin =1.5 × ULN.
14. Subjects with other abnormal laboratory test results, vital sign results, or ECG
findings unless, based on the investigator's judgment, the findings are not medically
significant and would not impact the safety of the subjects or the interpretation of
the trial results. The medical monitor should be contacted to discuss individual
cases, as needed.
Tests with exclusionary results should be repeated to ensure reproducibility of the
abnormality before excluding a subject based on criteria provided in the protocol. For
ECGs, 3 consecutive recordings are required and if 2 of the 3 remain exclusionary,
then the subject is not eligible for the trial.
- Disallowed Prior and Concomitant Medications
15. Subjects taking other prohibited medication or who would be likely to require
prohibited concomitant therapy during the trial.
- Other
16. Subjects with difficulty swallowing.
17. Subjects who are known to be allergic or hypersensitive to the IMP or any of its
components.
18. Subjects who are known to be allergic or hypersensitive to contents of the standard
diet.
19. Subjects who have participated in any clinical trial involving administration of an
investigational drug (new chemical entity) in the past 30 days or 5 half-lives (if
known) prior to dosing.
20. Receipt of blood products within 2 months prior to Check-in.
21. Donation of blood from 56 days prior to Screening, plasma from 2 weeks prior to
Screening, or platelets from 6 weeks prior to Screening.
22. Poor peripheral venous access.
23. Subjects with exposure to significant diagnostic or therapeutic radiation (eg, 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.
24. Subjects who have participated in a radiolabeled drug trial where exposures are known
to the investigator within the previous 4 months prior to admission to the clinic for
this trial or participated in a radiolabeled drug trial where exposures are not known
to the investigator within the previous 6 months prior to admission to the clinic for
this trial. The total 12-month exposure from this trial and a maximum of 2 other
previous radiolabeled trials within 4 to 12 months prior to this trial will be within
the CFR recommended levels considered safe, per US Title 21 CFR 361.1: less than 5,000
mrem whole body annual exposure with consideration given to the half-lives of the
previous radiolabeled trial drugs received.
25. Any subject who, in the opinion of the sponsor, investigator, or medical monitor,
should not participate in the trial.
26. Subjects who are investigational site staff members directly involved in the conduct
of the trial and their family members, site staff members otherwise supervised by the
investigator.
27. Unwilling or unable to comply with the lifestyle modifications described in this
protocol.
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