| Eligibility |
TARGET POPULATION:
INCLUSION:
Subjects must meet all the following inclusion criteria to be eligible:
1. Male or female between 18 and 45 years of age, inclusive, at time of informed consent.
1. Female subjects of childbearing potential must be non-lactating, not pregnant as
confirmed by a negative urine pregnancy test at Screening and admission to
Clinical Research Unit, and using, and agree to continue using, an effective
method of contraception for at least 4 weeks prior to first study drug
administration until 30 days after the last dose of study drug.
2. Female subjects of non-childbearing potential must be surgically sterile (e.g.,
hysterectomy, bilateral tubal ligation, oophorectomy) or post-menopausal (no
menses for >1 year with follicle stimulating hormone >40 U/L at Screening)
3. Female subjects of childbearing potential must not donate ova during the study
and for at least 30 days after the last dose of study drug.
4. Male subjects who have not had a vasectomy and/or Subjects who have had a
vasectomy but have not had 2 post surgery negative tests for sperm must agree to
use an acceptable method of contraception from time of first dose of study drug
until 30 days after the last dose of the study drug, and to not donate sperm
during the study and for at least 30 days after the last dose of study drug.
2. Healthy per investigator judgment as documented by medical history, physical
examination, vital sign assessments, 12-lead ECG, clinical laboratory assessments, and
general observations.
1. At Screening, abnormalities or deviations outside the normal ranges for any
clinical assessments that are considered clinically significant by the
Investigator (laboratory tests, ECG, vital signs) may be repeated once at the
discretion of the Investigator(s), and results that continue to be outside the
normal ranges must be judged by the investigator to be not clinically significant
and acceptable for study participation.
2. On admission to Clinical Research Unit, alanine aminotransferase (ALT), aspartate
aminotransferase (AST), total bilirubin, and thyroid values must be within the
upper limits of the normal range. Subjects with isolated elevation of bilirubin
and presumptive Gilbert's syndrome are permissible. All other laboratory test
results that are outside the reference range on admission to CRU and judged by
the investigator to be not clinically significant may optionally be repeated.
Results that continue to be outside the reference range must be judged by the
investigator to be not clinically significant and acceptable for study
participation.
3. Subject must demonstrate clinical euthyroidism as assessed by a thyroid profile
utilizing TSH and Free T4 testing at screening.
3. Body mass index between 18.0 and 30.0 kg/m2, with a minimum body weight of 45 kg for
females and 50 kg for males, inclusive. Additional inclusion criteria for the high BMI
single dose cohort:
a. Body mass index > 30.0 kg/m2, waist circumference > 41"
4. Understands the procedures and requirements of the study and provides written informed
consent and authorization for protected health information disclosure.
5. Willing and able to comply with the requirements of the study protocol.
EXCLUSION:
Subjects presenting with any of the following will not qualify for entry into the study:
1. Current or past clinically significant history of cardiovascular, cerebrovascular,
pulmonary, gastrointestinal, hematologic, renal, hepatic, immunologic, metabolic,
urologic, neurologic, dermatologic, psychiatric, or other major disease, as determined
by the investigator. History of cancer (except treated non-melanoma skin cancer) or
history of chemotherapy use within 5 years prior to Screening.
2. Any surgical or medical condition or history that, in the opinion of the investigator,
may potentially alter the absorption, metabolism, or excretion of study treatment,
such as, but not limited to gastric bypass surgery or small bowel resections.
3. Contraindication to study drug or its excipients and/or history of allergic or
anaphylactic reactions.
4. Resting heart rate <45 or >100 bpm; blood pressure < 90 or >140 systolic, or <50 or
>100 diastolic.
5. On screening ECG and by history:
1. A marked baseline prolongation of QT/QTcF interval (e.g., repeated demonstration
of a QTc interval > 450 msec for males and >470 msec for females).
2. A history of additional risk factors for Torsades de Pointes (TdP) (e.g., heart
failure, hypokalemia, family history of Long QT Syndrome).
6. Taking any of the following prohibited medications:
For non-obese cohorts:
a. Any prescription medication (with the exception of all hormonal contraceptives and
hormone replacement therapies (oral, injectable, transdermal or implanted)) or over
the counter multi-vitamin supplement, including products with CBD or any
non-prescription products (including herbal-containing preparations but excluding
acetaminophen) within 14 days prior to admission to CRU.
For obese cohort:
a. Limited background prescription medications are permitted to manage complications
of obesity, but any drug known to inhibit or induce cytochrome P450 (CYP) enzymes
and/or P-glycoprotein including St. John's wort (Hypericum perforatum) within 14 days
or 5 half-lives (whichever is longer) prior to admission to CRU, is prohibited. Also
prohibited is the use of concomitant medications that prolong the QT/QTc interval
identified in the https://crediblemeds.org/ website list category of 'Known Risk'.
7. History of significant drug abuse within one year prior to Screening or use of soft
drugs (such as marijuana) within 3 months prior to the Screening visit or hard drugs
(such as cocaine, phencyclidine [PCP], opioid derivatives including heroin, and
amphetamine derivatives) within 1 year prior to screening.
8. 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 of Screening.
9. Positive urine drug or urine alcohol test at Screening or on admission to CRU.
10. Current nicotine use or vaping regularly more than 5 cigarettes or the equivalent per
week.
11. Consumed any food or drink/beverage containing grapefruit or grapefruit juice, apple
or orange juice, pomelo juice, star fruit, Seville or Moro (blood) orange products
within 6 days before admission to CRU. Vegetables from the mustard green family (e.g.,
kale, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, mustard), food
containing poppy seeds (e.g., muffins, bagels, and cakes) must not be consumed within
24 hours before admission to CRU.
12. Positive test results of hepatitis B surface antigen (HBsAg), hepatitis C virus
antibody (HCV Ab), or human immunodeficiency virus (HIV1/2) antibody.
13. Diabetes reflected by a fasting plasma glucose level of =126 mg/dL and a reflex HbA1c
of =6.5%.
14. Participation in another clinical trial at the time of screening or exposure to any
investigational agent within 30 days or 5 half-lives prior to admission to CRU,
whichever is longer.
15. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding
volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than
499 mL within 56 days prior to the first dosing.
16. Received a tattoo or body piercing (including ear piercings) within 2 months prior to
Day 1, and/or significant open wound that may result in risk of infection.
17. Having a condition that the investigator believes would interfere with his/her ability
to provide written informed consent, comply with study instructions, or which might
confound the interpretation of the study results or put the subject at undue risk.
Subjects with a history of hypo- or hyperthyroidism, peripheral neuropathy, malignant
hyperthermia or chronic recurrent rash that is considered clinically significant by
the investigator are excluded.
18. Must not be claustrophobic or have a history of claustrophobia, or intolerance of
closed or small spaces.
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