| Eligibility |
Inclusion Criteria:
1. Male or female, smoker (no more than 25 cigarettes or equivalent daily) or non-smoker,
=18 and =60 years of age, with BMI >18.5 and <30.0 kg/m2 and body weight =50.0 kg for
males and =45.0 kg for females.
2. Healthy as defined by:
1. The absence of clinically significant illness. Subjects vomiting within 24 hours
pre dose will be carefully evaluated for upcoming illness/disease. Inclusion pre
dosing is at the discretion of the Investigator;
2. The absence of clinically significant history of dermatological, neurological,
endocrine, cardiovascular, respiratory, hematological, immunological,
psychiatric, gastrointestinal, renal, hepatic, and metabolic disease.
3. Females of childbearing potential who are sexually active with a male partner must be
willing to use one of the following acceptable contraceptive methods throughout the
study and for 30 days after the last study drug administration:
1. Intra-uterine contraceptive device without hormone release system placed at least
4 weeks prior to study drug administration;
2. Male condom with intravaginally applied spermicide started at least 21 days prior
to study drug administration;
3. Sterile male partner (vasectomized since at least 6 months).
4. Absence of excessive body hair at the topical application site, or willing to have
excess body hair removed prior to dosing.
5. Capable of consent.
Exclusion Criteria:
1. Presence of any clinically significant abnormality at physical examination, clinically
significant abnormal laboratory assessment or positive test for hepatitis B, hepatitis
C, or HIV found during medical screening.
2. Positive urine drug screen or alcohol breath test at screening.
3. History of allergic reactions to tofacitinib or other related drugs, or to any
excipient in the formulation.
4. Positive pregnancy test at screening.
5. Clinically significant ECG abnormalities or vital sign abnormalities (systolic blood
pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 50 or
over 90 mmHg, or heart rate less than 50 or over 100 bpm) at screening.
6. History of significant alcohol abuse within 1 year prior to screening or regular use
of alcohol within 6 months prior to the screening visit (more than 14 units of alcohol
per week [1 unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol]).
7. History of significant drug abuse within 1 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], crack, opioid derivatives including heroin, and
amphetamine derivatives) within 1 year prior to screening.
8. Participation in a clinical research study involving the administration of an
investigational or marketed drug or device within 30 days prior to the first dosing,
administration of a biological product in the context of a clinical research study
within 90 days prior to the first dosing, or concomitant participation in an
investigational study involving no drug or device administration.
9. Use of medications for the timeframes specified below, with the exception of
medications exempted by the Investigator on a case-by-case basis because they are
judged unlikely to affect the pharmacokinetic profile of the study drug or subject
safety e.g. topical drug products without significant systemic absorption (not
including topical drug products administered to the gel application site):
1. Prescription medications within 14 days prior to the first dosing;
2. Over-the-counter products and natural health products (including herbal remedies,
homeopathic and traditional medicines, probiotics, food supplements such as
vitamins, minerals, amino acids, essential fatty acids, and protein supplements
used in sports) within 7 days prior to the first dosing, with the exception of
the occasional use of acetaminophen (up to 2 g daily);
3. Depot injection or implant of any drug within 3 months prior to the first dosing;
4. Any drugs known to induce or inhibit hepatic drug metabolism via the CYP3A4 and
CYP2C19 enzymes within 30 days prior to first dose;
- Examples of inducers for CYP3A4 include barbiturates, carbamazepine,
phenytoin, glucocorticoids, St. John's wort, etc.
- Examples of inhibitors for CYP3A4 include HIV antivirals, clarithromycin,
ciprofloxacin, gestodene, etc.
- Examples of inducers for CYP2C19 include carbamazepine, norethindrone,
prednisone, rifampicin, etc.
- Examples of inhibitors for CYP2C19 include proton pump inhibitors,
fluoxetine, ketoconazole, etc.
10. 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.
11. Breast-feeding subject.
12. History of active tuberculosis or exposure to endemic areas within 8 weeks prior to
QuantiFERON®-TB testing performed at screening.
13. Positive QuantiFERON®-TB indicating possible tuberculosis infection.
14. Immunization with a live attenuated vaccine within 1 month prior to dosing or planned
vaccination during the course of the study.
15. History of clinically significant opportunistic infection e.g. invasive candidiasis or
pneumocystis pneumonia.
16. Serious local infection e.g. cellulitis, abscess, or systemic infection e.g.
septicemia, within 3 months prior to screening.
17. Presence of fever (body temperature >37.6 °C) e.g. a fever associated with a
symptomatic viral or bacterial infection, within 2 weeks prior to the first dosing.
18. Presence of sunburn at the gel application site, or excessive exposure to ultraviolet
light such as sunlight or a tanning lamp, or recent use of laser at the gel
application areas that would prevent a safe application of the gel formulation as
judged by the Investigator, within 7 days before the gel application.
19. Presence of tattoos or significant skin aberrations at the gel application site, which
in the opinion of the investigator, would interfere with the ability to perform an
accurate dermal reaction assessment.
20. Any reason that, in the opinion of the Investigator, would prevent the subject from
participating in the study.
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