| Eligibility |
Inclusion Criteria:
1. Sex : male or female; females must be of non-childbearing potential, or
postmenopausal.
2. Age : 18 to 55 years, inclusive, at screening.
3. Body mass index (BMI) : 18.0 to 32.0 kg/m^2, inclusive, at screening.
4. Weight : =50 kg, inclusive, at screening.
5. Status : healthy participants. Healthy status as defined by the absence of evidence of
any clinically significant, in the opinion of the investigator, active, or chronic
disease.
6. Male participants and female participants of childbearing potential must agree to use
protocol specified methods of contraception and comply with pregnancy precautions as
described in the protocol.
7. All prescribed medication must have been stopped at least 14 days prior to admission
to the clinical site.
8. All over-the-counter medication, vitamin preparations and other food supplements, or
herbal medications (e.g., St. John's wort) must have been stopped at least 7 days (or
5 half-lives for certain medications, whichever is longer) prior to admission to the
clinical site. Occasional use of acetaminophen/paracetamol (e.g., up to 2 grams per
day) is permitted during this period and throughout the study.
9. Ability and willingness to abstain from alcohol-, caffeine-, and
methylxanthine-containing beverages or food (e.g., coffee, tea, cola, chocolate,
energy drinks) from 48 hours (2 days) prior to admission to the clinical site and
during confinement at the clinical site.
10. Willingness to abstain from any strenuous physical exercise from 96 hours (4 days)
prior to admission and during confinement at the clinical site.
11. Good physical and mental health on the basis of medical history, physical examination,
clinical laboratory assessments, 12-lead electrocardiogram (ECG), Columbia-Suicide
Severity Rating Scale (C-SSRS) (Cohort 2 only) and vital signs, as judged by the
Investigator.
12. Willing and able to sign the informed consent form (ICF).
Exclusion Criteria:
1. Employee of ICON or the Sponsor.
2. History of relevant drug and/or food allergies, in the opinion of the Investigator.
3. Females who are currently breastfeeding.
4. Smoking more than 5 cigarettes, 1 cigar, or 1 pipe daily within 3 months prior to
screening.
5. Unwilling or unable to abstain from tobacco products within the 48 hours (2 days)
prior to admission and during confinement at the clinical site.
6. History of alcohol abuse or drug addiction (including soft drugs like cannabis
products) within 1 year prior to screening.
7. Positive drug and/or alcohol screen (opiates, methadone, cocaine, amphetamines
[including ecstasy], cannabinoids, barbiturates, benzodiazepines, tricyclic
antidepressants, and alcohol) at screening or admission to the clinical site.
8. History within the previous 12 months of alcohol consumption exceeding 2 standard
drinks per day on average. Alcohol consumption will be prohibited 48 hours prior to
admission to the clinical facility and until discharge in the study period.
9. Positive screen for hepatitis B surface antigen, hepatitis C virus (HCV) antibodies,
or human immunodeficiency virus (HIV) 1 and 2 antibodies.
10. Consumption of any nutrients known to modulate cytochrome P450 (CYP450) enzymes
activity (e.g., grapefruit or grapefruit juice, pomelo juice, star fruit, or Seville
[blood] orange products) within 14 days prior to the first administration of study
drug and during the study (including washout period/clinic furlough until after
discharge in the last study period).
11. Participation in a drug study within 30 days prior to study drug administration in the
current study. Participation in 4 or more other drug studies in the 12 months prior to
study drug administration in the current study.
12. History of donation of more than 450 mL of blood within 60 days prior to dosing in the
clinical site or planned donation before 30 days has elapsed since intake of study
drug.
13. Plasma or platelet donation within 7 days of dosing and through follow-up.
14. Significant and/or acute illness within 5 days prior to study drug administration that
may impact safety assessments, in the opinion of the Investigator.
15. Unsuitable veins for infusion or blood sampling as determined by the Investigator or
study staff.
16. Any other condition or prior therapy that, in the Investigator's opinion, would
confound or interfere with the evaluation of safety, tolerability, or pharmacokinetics
(PK) of the study drug, interfere with study compliance, or preclude informed consent.
Cohort 2 Only:
17. Individuals who have Asian ancestry (including those who have one or more Asian
grandparents).
18. Presence of active suicidal ideation or positive suicide behavior using the
"Baseline/Screening" version of the C-SSRS and with either of the following criteria:
- History of a suicide attempt within the 5 years prior to the Screening Visit.
Participants with a history of a suicide attempt more than 5 years ago should be
evaluated by a mental healthcare professional (e.g., locally licensed
psychiatrist, psychologist, or master's level therapist) before enrolling into
the study.
- Suicidal ideation in the past month prior to the Screening Visit as indicated by
a positive response ("Yes") to either Question 4 or 5 of the "Baseline/Screening"
version of the C-SSRS.
19. History of epilepsy.
20. Leukopenia (white blood cell count <lower limit of normal [LLN]), neutropenia
(neutrophil count <LLN), or thrombocytopenia (platelet count <LLN), at screening or
admission (Day -1).
|
