| Eligibility |
Inclusion Criteria:
1. Males and non-pregnant, non-lactating females, 18-80 years of age, inclusive.
2. A minimum body weight of 60 kg and a Body Mass Index (BMI) of 18.5-29.9 kg/m²,
inclusive. BMI will be calculated using Novum Pharmaceutical Research Services
Standard Operating Procedures.
3. Female subjects must meet at least one of the following requirements:
- Agree to abstain from sexual intercourse from screening and throughout the
duration of the study, including washout periods, and for 30 days after the last
study drug administration.
- Have used and agree to continue to use a reliable method of hormonal
contraception (oral, implanted, or injected) in conjunction with a barrier method
(e.g., diaphragm, cervical cap, male condom, and female condom and spermicidal
foam, sponges, and film) for at least 30 days before initial dosing and
throughout the duration of the study, including washout periods, and for 30 days
after the last study drug administration.
- Have used and agree to continue to use an intrauterine device (IUD) at least 3
months before initial dosing and throughout the duration of the study, including
washout periods, and for 30 days after the last study drug administration.
- Surgically sterile (bilateral oophorectomy or hysterectomy, bilateral tubal
ligation at least 3 months before initial dosing or Essure® device placement
before the year 2018).
- At least 2 years postmenopausal and have a documented follicle stimulating
hormone (FSH) level = 40 milli-international units per milliliter (mIU/mL) at
screening.
4. Male subjects who are not surgically sterile must agree to abstain from sexual
intercourse (complete abstinence) or use appropriate contraceptive measures and agree
to not impregnate a female partner(s) and not to donate sperm throughout the entire
study, including the washout periods, and for 30 days after the last study drug
administration. Examples of acceptable methods of contraception include a
double-barrier method of contraception (e.g., condom with spermicide). Other forms of
contraception may be acceptable, at the discretion of the Investigator.
5. Subject is judged by an Investigator to be in good health as determined by lack of
clinically significant abnormalities in health assessments performed at screening. Any
abnormalities or deviations outside the normal ranges for any clinical testing (e.g.,
laboratory tests, ECG, vital signs) may be repeated, at the discretion of the
Investigator(s), and judged by an Investigator to be not clinically significant for
study participation.
6. Subject doesn't have any relevant dietary restrictions, as determined by the
Investigator, and is willing to consume a high-fat, high-calorie breakfast and other
standard meals provided during the treatment periods of the study, and to comply with
the fasting conditions required by the study design.
7. Subject is able to read and speak English fluently. Subjects will be required to read,
understand, sign and date the informed consent form, which meets all criteria of
current FDA regulations, and must be able to understand the information and
instruction given to them during the study.
Exclusion Criteria:
1. Females who are pregnant, lactating, or likely to become pregnant during the study.
2. History of allergy or sensitivity to apixaban, or history of any food or drug
hypersensitivity or intolerance which, in the opinion of the Investigator, would
compromise the safety of the subject or the study.
3. Current tongue piercing or other piercings in the mouth, including lips and cheeks
which have studs/rings, etc. or where the piercing wound is not completely closed or
any tongue or other oral deformities that may affect the absorption of the drug
product.
4. Significant history or current evidence of system disorders, organ dysfunction
especially cardiovascular disorders (e.g., atrial fibrillation), renal or hepatic
disorders.
5. Significant familial history of sudden cardiac death, as determined by the
Investigator.
6. Subject has a prosthetic heart valve.
7. Significant history or current evidence of blood clots or bleeding disorders (e.g.,
bleeding diathesis [tendency to bleed or bruise easily]), stroke, or active
pathological bleeding.
8. Clinically significant history or are currently at risk for arterial or venous
thromboembolic events (e.g., transient ischemic attack, cerebrovascular accident,
myocardial infarction, retinal artery occlusion or retinal vein thrombosis, pulmonary
embolism, deep vein thrombosis, antiphospholipid syndrome), as determined by the
Investigator.
9. Serum creatinine = 1.5 mg/dL.
10. Creatinine clearance (CrCl) < 50 mL/min; obtained from the clinical laboratory tests
performed at screening. CrCl can be estimated using the following (Cockcroft-Gault)
equation:
CrCl= ((140-age) × actual weight(kg) × [0.85 if female])/(SerumCr(mg/dL) × 72)
11. Clinically significant history or presence of gastrointestinal disease (e.g.,
bleeding, perforation, or fistulas) or malabsorption, as determined by the
Investigator.
12. Subject has had an acute infection within 2 weeks before screening or at any time
between screening and check-in including, but not limited to, history, signs, or
symptoms of a common cold (e.g., mild rhinorrhea), untreated oral/dental abnormalities
(e.g., untreated dental caries as determined by examination of the mouth), or
untreated disruption of the skin, as determined by the Investigator.
13. Subject has an active infection requiring systemic therapy at the time of screening,
which is considered clinically significant by the Investigator.
14. Subject has a significant history of or ongoing chronic or recurrent infectious
disease (e.g., infected indwelling prosthesis, osteomyelitis, chronic sinusitis), as
determined by the Investigator.
15. Anticipating undergoing surgery or medical/dental procedure, receiving neuraxial
anesthesia (spinal/epidural anesthesia), or undergoing spinal puncture during the
study or within 7 days after study completion.
16. History of psychiatric disorders occurring within the last two years, which required
the subject to be hospitalized or treated with medication.
17. Presence of a medical condition requiring regular treatment with prescription drugs
(except hormonal contraceptives).
18. Use of pharmacologic agents or herbal products known to significantly induce or
inhibit drug-metabolizing enzymes (especially inhibitors and inducers of CYP3A4 and
P-gp such as ketoconazole, itraconazole, ritonavir, clarithromycin, rifampin,
phenytoin, carbamazepine, St. John's Wort, etc.) within 30 days before initial dosing.
19. Use of drugs affecting hemostasis such as aspirin and other antiplatelet agents, other
anticoagulants, heparin, thrombolytic agents, selective serotonin reuptake inhibitors
(SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and nonsteroidal
anti-inflammatory drugs (NSAIDs) within 14 days before initial dosing.
20. Receipt of any drug as part of a research study within 30 days before initial dosing.
21. Drug or alcohol addiction requiring treatment in the 12 months before initial dosing.
22. History of excessive alcohol consumption (on average more than 14 units of
alcohol/week; 1 unit = 12 oz. beer, 6 oz. wine, 1 shot [1.5 oz.] of liquor) during the
past 12 months.
23. Donation or significant loss of whole blood (480 mL or more) within 30 days or plasma
within 14 days before initial dosing.
24. Positive test for HIV, Hepatitis B surface antigen or Hepatitis C antibody.
25. Positive test results for drugs of abuse or cotinine at screening.
26. If female, has a positive pregnancy test at screening.
27. Difficulty swallowing, as determined by the Investigator.
28. Use of tobacco- or nicotine-containing products within 1 year before initial dosing.
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