Eligibility Details:
Inclusion Criteria:
1. Male or female and ≥ 18 to ≤ 55 years of age, at the time of signing the informed
consent form (ICF).
2. Capable of giving signed informed consent
3. Body mass index (BMI) ≥ 18.5 to < 32.0 kg/m² at the Screening visit．
4. Considered medically healthy as determined by the investigator or subinvestigator
(suitably qualified), based on medical history and clinical evaluations including
physical examination, clinical laboratory tests, vital sign measurements, and 12-lead
ECG at Screening and at upon admission to the Clinical Research Unit (CRU) and prior
to administration of study intervention on Day 1.
5. Female study participants must not be a woman of childbearing potential and must
either be postmenopausal (defined as no menses for 12 months without an alternative
medical cause; follicle-stimulating hormone (FSH) to be tested for confirmation at
Screening) or premenopausal with 1 of the following documented: hysterectomy, tubal
ligation, bilateral salpingectomy, or bilateral oophorectomy.
6. Male study participants must agree to use contraception during the treatment period
and for at least 3 months after the last dose of study intervention.
Exclusion Criteria:
1. Considered by the investigator or subinvestigator (suitably qualified) to be
ineligible for the study due to a history of or current condition of significant
metabolic or endocrine, hepatic, renal, hematological, pulmonary, cardiovascular,
gastrointestinal (GI), urological, immunological, neurological, or psychiatric
disorders with clinical manifestations.
2. History or presence of cancer in last 5 years except for nonmelanoma skin cancers.
3. Risk factors for:
1. Torsades de Pointes (eg, heart failure, cardiomyopathy, or family history of Long
QT Syndrome or Brugada Syndrome)
2. Unexplained syncope, sick sinus syndrome, second- or third-degree
atrioventricular (AV) block, myocardial infarction, pulmonary congestion, cardiac
arrhythmia, angina, prolonged QT interval, or conduction abnormalities
4. History of GI surgery or disease including, but not limited to, gastric band/gastric
resection and/or intestinal resection and/or duodenal disease (ie, celiac disease)
that may result in clinically significant malabsorption (except for an appendectomy).
5. History of hypersensitivity or severe side effects induced by a drug.
6. Any condition requiring medication and/or other treatment, such as dietary restriction
and physical therapy.
7. History of significant multiple and/or severe allergic symptoms including food allergy
(NOTE: Study participants with seasonal allergies may participate unless they have
ongoing symptoms).
8. Used drugs or substances known to be inducers or inhibitors of cytochrome P450 enzymes
and/or P-glycoprotein within 28 days prior to admission to the CRU.
9. Used prescription or over-the-counter (OTC) drugs, antacids, proton pump inhibitors,
H2 antagonists, Chinese herbal medicines, oral cannabidiol, vitamins, minerals,
herbal, and dietary supplements within 14 days prior to admission to the CRU.
10. Refuses to abstain from ingesting caffeine- or xanthine-containing
products/medications (eg, coffee, tea, cola drinks, other caffeinated beverages, or
chocolate) from 24 hours prior to admission to the CRU or refuses to refrain from
consuming such products throughout the study (including Follow-up period).
11. Consumed alcohol or used alcohol-containing products within 72 hours prior to
admission to the CRU or refuses to refrain from consuming such products throughout the
study (including Follow-up period).
12. History of recreational drug use in the previous 6 months, or has a history of
problematic alcohol use (defined as study participants who regularly consume excessive
amounts of alcohol, defined as > 3 glasses of alcoholic beverages per day (1 glass is
approximately equivalent to: beer [284 mL/10 ounces (oz.)], wine [125 mL/4 oz.] or
distilled spirits [25 mL/1 oz.]).
13. A positive drug or alcohol screen at the Screening visit or upon admission to the CRU.
14. Used tobacco- or nicotine-containing products (including cigarette, pipe, cigar,
chewing, nicotine patch, nicotine gum, or Vaping product) within 6 months prior to
admission to the CRU or refuses to refrain from using tobacco- or nicotine-containing
products throughout the study (including Follow-up period).
15. Consumed grapefruit, grapefruit juice, Seville orange juice, orange juice, apple
juice, vegetables from the mustard green family (eg, kale, broccoli, watercress,
collard greens, kohlrabi, Brussels sprouts, mustard greens), or charbroiled meats
within 7 days prior to admission to the CRU or refuses to refrain from consuming such
products throughout the study (including Follow-up period).
16. A corrected QT (QTc) interval of > 450 msec for males and > 470 msec for females
(Fridericia's method) at the Screening visit or upon admission to the CRU.
17. Systolic blood pressure is outside the range of 90 to 140 mm Hg, diastolic blood
pressure is outside the range of 50 to 90 mm Hg, or pulse rate is outside the range of
40 to 100 beats per minute (bpm) or considered ineligible by the investigator or
subinvestigator at the Screening visit or upon admission to the CRU.
18. Total bilirubin, alanine aminotransferase (ALT), or aspartate aminotransferase (AST)
values are greater than the upper limit of normal (ULN), or estimated glomerular
filtration rate (eGFR) < 90 mL/min/1.73 m² at Screening or upon admission to the CRU.
19. A positive serological test for untreated syphilis, positive hepatitis B surface
antigen, positive hepatitis C virus antibody, or positive human immunodeficiency virus
(HIV) antigen/antibody result at the Screening visit.
20. Participated in any other investigational trials or has been exposed to other
investigational drugs within 28 days or 5 half-lives of the previously administered
investigational drug (date derived from last study procedure [blood collection or
dosing] of previous trial), whichever is longer, prior to admission to the CRU.
21. Previously received S-648414.
22. Poor venous access.
23. Donated blood or had significant blood loss within 56 days of study admission to the
CRU or donated plasma within 7 days prior to until admission to the CRU.
24. Considered inappropriate for participation in the study for any reason by the
investigator or subinvestigator.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
