| Eligibility |
Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study:
1. Subject must understand and voluntarily sign an informed consent form (ICF) prior to
any study-related assessments/procedures being conducted.
2. Subject must be willing and able to communicate with the Investigator and adhere to
the study visit schedule and other protocol requirements.
3. Subject is male or female of any race = 18 to = 65 years of age at the time of signing
the ICF.
4. Female subjects NOT of childbearing potential must:
a. Have been surgically sterilized (hysterectomy or bilateral oophorectomy; proper
documentation required) at least 6 months before Screening, or postmenopausal (defined
as 24 consecutive months without menses before Screening, with a follicle-stimulating
hormone [FSH] level in the post-menopausal range according to the laboratory used at
Screening).
5. Females of childbearing potential (FCBP1) must:
1. Have a negative pregnancy test as verified by the investigator at Screening and
Baseline (prior to starting study treatment). She must agree to ongoing pregnancy
testing during the course of the study and after end of study treatment. This
applies even if the subject practices true abstinence2 from heterosexual contact.
2. Either commit to true abstinence from heterosexual contact (which must be
reviewed on a monthly basis, as applicable, and source documented) or agree to
use, and be able to comply with, any one of the following highly effective
contraception methods without interruption, beginning at least 14 days prior to
starting investigational product (IP), during the study treatment, and for at
least 30 days after the last dose of IP.
- Intrauterine device (IUD; non-hormonal only); tubal ligation; or a partner
with a vasectomy. The chosen form of birth control must be effective by the
time the subject receives the first dose of IP.
6. Male subjects must:
a. Practice true abstinence from heterosexual contact (which must be reviewed on a
monthly basis, as applicable, and source documented) or agree to use a barrier method
of birth control (condoms not made from natural [animal] membrane [latex condoms are
recommended]) during sexual contact with a pregnant female or FCBP while receiving
study treatment, and for at least 30 days after the last dose of IP, even if he has
undergone a successful vasectomy.
7. Must have a body mass index (BMI) = 18 and = 33 kg/m2 at screening.
8. Must be healthy, as determined by the Investigator on the basis of medical history,
physical examination (PE), clinical laboratory test results, vital signs, and 12-lead
electrocardiogram (ECG) at screening and check-in (Day -1), as applicable:
Aspartate aminotransferase (AST), ALT, and total bilirubin must be at or below the
upper limit of the reference range on or before check-in (Day -1). Other clinical
laboratory results must be either within normal range or deemed not clinically
significant by the Investigator. Any out of range lab tests may be repeated up to 1
time during Screening and up to 1 time at check-in per Investigator discretion to
confirm eligibility.
9. Must be afebrile (febrile is defined as = 38°C or 100.3°F).
10. Supine systolic blood pressure (BP) must be in the range of 90 to 150 mmHg
(inclusive), supine diastolic BP must be in the range of 50 to 90 mmHg (inclusive),
and pulse rate must be in the range of 45 to 90 bpm (inclusive) at Screening. Any out
of range vital sign measurements may be repeated up to 1 time during Screening and up
to 1 time at check-in per Investigator discretion to confirm eligibility.
11. Subject has a normal or clinically acceptable 12-lead ECG at screening; male subjects
must have a corrected QT interval using Fridericia's formula (QTcF) value = 430 msec
and females must have a QTcF value = 450 msec. An ECG may be repeated up to 2 times,
and the average of the QTcF values will be used to determine subject eligibility.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
1. History (within 3 years prior to Screening) of any clinically significant
neurological, GI, hepatic, renal, respiratory, cardiovascular, metabolic, endocrine,
hematological, dermatological, psychological, or other major disorders as determined
by the Investigator.
2. Any condition, including the presence of laboratory abnormalities, that places the
subject at unacceptable risk if he or she were to participate in the study or
confounds the ability to interpret data from the study (congenital nonhemolytic
hyperbilirubinemia [eg, Gilbert's syndrome] is not acceptable).
3. Subject has prior history of Wernicke's Encephalopathy (WE).
4. Subject has signs or symptoms of WE (eg, ataxia, ocular paralysis, or cerebellar
signs) without documented exclusion of WE by thiamine level and brain magnetic
resonance imaging (MRI).
5. Subject has thiamine deficiency, defined as thiamine levels in whole blood below
normal range according to institutional standard.
6. Use of any prescribed systemic or topical medication, including vaccines, within 30
days of the first dose administration (with the exception of ondansetron administered
for purposes of this study).
7. Use of any nonprescribed systemic or topical medication (including vitamin/mineral
supplements and herbal medicines) within 14 days of the first dose administration
(with the exception of acetaminophen up to 2 grams/day for no more than 3 consecutive
days to treat minor illness or headache [per Investigator judgment]).
8. Use of any metabolic enzyme or relevant transporter inhibitors or inducers that would
affect the relevant drugs within 30 days of the first dose administration unless
determined by the Investigator that there will be no impact on the study integrity or
subject safety.
The Indiana University "P450 Drug Interaction Table" should be used to determine
inhibitors and/or inducers of metabolic enzymes
(http://medicine.iupui.edu/clinpharm/ddis/table/aspx). The Sponsor should be contacted
for questions about potential drug-drug interactions and exclusions/prohibitions when
necessary.
9. Exposure to an investigational drug (new chemical entity) within 30 days preceding the
first dose administration or 5 half-lives of that investigational drug, if known
(whichever is longer).
10. Presence of any surgical or medical conditions possibly affecting drug absorption,
distribution, metabolism, and excretion (eg, bariatric procedure, cholecystectomy).
Appendectomy is acceptable.
11. Donated blood or plasma within 8 weeks before the first dose administration.
12. History of drug abuse (as defined by the current version of the Diagnostic and
Statistical Manual [DSM]) within 2 years before dosing or positive drug screening test
reflecting consumption of illicit drugs.
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