Eligibility Details:
Inclusion Criteria:
1. Males or females, of any ethnic origin, between 18 and 45 years of age, inclusive, at
Screening.
2. Body mass index between 18.0 and 32.0 kg/m2, inclusive, at Screening.
3. In good health, determined by no clinically significant findings from medical history,
physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory
evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspected Gilbert's
syndrome, as determined by total bilirubin and indirect bilirubin] is acceptable) at
Screening and/or Check-in, as assessed by the Investigator.
4. Male subjects must be surgically sterile for at least 90 days or, for males capable of
fathering children who are sexually active with female partners of childbearing
potential, will use the required contraception methods, and will refrain from donating
sperm from the time of the first dose until 90 days after the final dosing occasion.
5. Female subjects must be:
- postmenopausal, defined as at least 12 months post cessation of menses (without
an alternative medical cause) with a screening serum follicle-stimulating hormone
(FSH) level > 40 mIU/mL, or
- permanently sterile following hysterectomy, Essure procedure, bilateral
salpingectomy, bilateral oophorectomy, or confirmed tubal occlusion (not tubal
ligation).
6. Venous access sufficient for IV infusions.
7. Able to comprehend and willing to sign an Informed Consent Form (ICF) and to abide by
the study restrictions.
Exclusion Criteria:
1. Female subjects who are pregnant or lactating.
2. Have any clinically significant abnormal physical examination finding at Check-in.
3. Have any clinically significant medical history, as determined by the Investigator.
4. History of seizure disorder, even if currently not receiving anticonvulsant
medications.
5. Part B only: Have acute suicidality, as evidenced by answering "yes" for Question 4 or
Question 5 on the C-SSRS, indicating active suicidal ideation with any intent to act
at Screening and Check-in.
6. Part B only: Have a history of suicidal behavior such that a determination of "yes" is
made on the Suicidal Behavior section of the C-SSRS for "Actual Attempt," "Interrupted
Attempt," "Aborted Attempt," or "Preparatory Acts or Behavior" at Screening and
Check-in.
7. History or clinical manifestations of clinically significant metabolic (including
diabetes mellitus, hypercholesterolemia, or dyslipidemia), hematologic, pulmonary,
cardiovascular, gastrointestinal (cholecystectomy and appendectomy are acceptable),
neurologic, hepatic, renal, urologic, immunologic, or psychiatric disorders (a history
of mild depression, currently not receiving therapy, is acceptable), as determined by
the Investigator.
8. Have any clinically significant allergic condition (excluding non-active hay fever),
as determined by the Investigator.
9. Have a significant history of drug allergy, as determined by the Investigator.
10. Have a clinically significant abnormality in oral temperature, respiratory rate, or
supine pulse rate or blood pressure at Screening and prior to first dose that, in the
opinion of the Investigator, increases the risk of participating in the study.
11. Electrocardiogram findings that meet any of the following criteria at Screening or
Day-1 (if out of range, ECG may be repeated twice, and the triplicate average will be
used):
- QTcF >450 msec confirmed by repeat measurement,
- QRS duration > 120 msec,
- PR interval >220 msec,
- findings which would make QTc measurements difficult or QTc data uninterpretable.
12. History of additional risk factors for torsades de pointe (eg, heart failure,
hypokalemia, family history of long QT syndrome).
13. Have clinically significant arrhythmias or sinus pauses identified in the continuous
12-lead ECG monitoring on Day -1, as determined by the Investigator.
14. Have any clinically significant abnormal laboratory safety findings at Screening and
Check-in, as determined by the Investigator or designee (one repeat assessment is
acceptable). Note: Liver function tests (eg, AST, ALT, total bilirubin, GGT) and
inflammatory response markers (eg, white blood cell and absolute neutrophil and
monocyte counts) must be within the normal range at Screening (one repeat assessment
is acceptable) (after Screening this will be as determined by the Investigator).
15. A positive hepatitis virus test (hepatitis B surface antigen or hepatitis C virus
antibody) or a positive human immunodeficiency virus antibody test (or p24 antigen) at
Screening.
16. Have had a clinically significant illness within 4 weeks of first dose, as determined
by the Investigator (or designee).
17. Alcohol consumption of > 21 units per week for males and > 14 units per week for
females. Note: One unit of alcohol equals 12 oz (360 mL) beer, 1.5 oz (45 mL) liquor,
or 5 oz (150 mL) wine.
18. Significant history of alcoholism or drug/chemical abuse, as determined by the
Investigator.
19. An active smoker or user of other forms of tobacco. Former smokers or tobacco users
must have refrained from smoking or using other forms of tobacco for at least 6 months
prior to dosing on Day 1 until the Follow-up visit.
20. Have donated blood from 90 days prior to Screening, platelets from 42 days prior to
Screening, or plasma from 7 days prior to Screening until 56 days after the Follow-up
visit.
21. Have received another investigational drug within 30 days prior to randomization.
22. Have received known inhibitors or inducers of CYP1A2 or any medications or herbal
remedies, including St. John's Wort, known to chronically alter drug absorption or
elimination processes within 30 days prior to first dose administration, until the
Follow-up visit, unless in the opinion of the Investigator (or designee), Medical
Monitor, and/or Aeromics, the medication will not interfere with the study procedures
or compromise safety.
23. Use of any prescription medications/products within 14 days prior to randomization, or
use of nonprescription, over-the-counter medication/products, including vitamins,
minerals, and phytotherapeutic/herbal/plant-derived preparations, within 7daysprior to
randomization until the Follow-up visit. Exceptions may be made by the Medical
Monitor, Investigator (or designee), and/or Aeromics on a case-by-case basis.
Intermittent use of acetaminophen at moderate daily doses (eg, ≤ 1g per day for ≤2
consecutive days) may be allowed at the discretion of the Investigator.
24. Positive urine drug screen at Screening (not including cotinine or alcohol) or
Check-in (including cotinine and alcohol), confirmed by repeat.
25. Consumption of foods and beverages containing poppy seeds, grapefruit, or Seville
oranges within 7 days prior to Check-in until the Follow-up visit.
26. Subjects unwilling to refrain from strenuous exercise from 7 days before Check- in
until the Follow-up visit.
27. Consumption of alcohol-containing foods and beverages within 72 hours prior to
Check-in until the Follow-up visit.
28. Consumption of caffeine-containing foods and beverages within 72 hours prior to
Check-in until discharge on Day 3 for Part A or on Day 12 for Part B.
29. Have previously taken part in or withdrawn from this study.
30. Subjects who, in the opinion of the Investigator, should not participate in this
study.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
