Eligibility Details:
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 to adhere to
the study visit schedule and other protocol requirements.
3. Subject must be a male or female of any race from ≥ 18 and ≤ 65 years of age at the
time of signing the informed Consent Form (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 (FCBP) 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, as applicable, and after end of study
treatment. This applies even if the subject practices true abstinence 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, during any dose interruptions, 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
ECG at screening and check-in (Day -1), as applicable:
Aspartate aminotransferase (AST), alanine aminotransferase (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 one time during the screening period and up to one 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 140 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 40 to 100 bpm (inclusive) at screening. Repeat
vital signs may be measured at investigator discretion.
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 two 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 (ie, within 3 years) 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, severe ataxia, ocular paralysis, or
cerebellar signs) without documented exclusion of WE by thiamine level and brain MRI.
5. Subject has thiamine deficiency, defined as thiamine levels in whole blood below
normal range according to institutional standard.
6. Subject has active tuberculosis or another disease caused by mycobacteria.
7. Use of any prescribed systemic or topical medication, including vaccines, within 30
days of the first dose administration (with the exception of any odansetron
administered for purposes of this study).
8. 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]).
9. Use of any metabolic enzyme 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. The sponsor should be contacted for
questions about potential drug-drug interactions and exclusions/prohibitions when
necessary.
10. 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).
11. Presence of any surgical or medical conditions possibly affecting drug absorption,
distribution, metabolism, and excretion (eg, bariatric procedure). Appendectomy and
cholecystectomy are acceptable.
12. Donated blood or plasma within 8 weeks before the first dose administration.
13. 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.
14. History of alcohol abuse (as defined by the current version of the DSM) within 2 years
before dosing or positive alcohol screen.
15. Known to have serum hepatitis; known to be a carrier of the hepatitis B surface
antigen (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody
(anti-HBc), or hepatitis C antibody (HCV Ab); have a positive result to the test for
hepatitis B or hepatitis C virus at screening or have a positive result to the test
for human immunodeficiency virus (HIV) antibodies at screening. Subjects whose results
are compatible with prior immunization (including natural and vaccination) against
hepatitis B may be included at the discretion of the investigator.
16. Use of tobacco- or nicotine-containing products within 3 months prior to check-in.
17. Subject has received live vaccination (excluding seasonal flu vaccination) within 90
days of first dosing.
18. History of multiple drug allergies (ie, two or more).
19. Allergic to or hypersensitive to any of the drugs used in the part of the study in
which the subject will participate.
20. Has any medical condition, medical history, or use of concomitant medication that is
contraindicated in the applicable drug labeling.
21. Female subject who is pregnant or breastfeeding.
22. Subject is part of the clinical staff personnel or a family member of the clinical
site staff.
23. Subject has a hypersensitivity to ondansetron.
24. History of severe or serious psychiatric disease ever requiring hospitalization or use
of antipsychotic/neuroleptic medications, history of suicidal ideation or suicidal
attempt, or undergoing psychiatric treatment will be excluded from study
participation.
25. Subject deemed by the investigator or medical professional to be a fall risk.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
