- Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the study
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests and
other study procedures
- Healthy female subjects and/or male subjects who, at the time of screening, are
between the ages of 18 and 55 years, inclusive
- Female subjects with child-bearing potential must not be intending to become pregnant,
currently pregnant, or lactating. Conditions apply: negative pregnancy test, effective
method of contraception
- Non-childbearing potential must meet at least 1 of the following criteria: documented
hysterectomy and/or bilateral oophorectomy, ovarian failure, achieved postmenopausal
status confirmed with FSH
- Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lbs)
- Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, GI, CV, hepatic, psych, neurological, or allergic disease (including drug
allergies, but excluding seasonal)
- Evidence or history of clinically significant dermatological condition (eg, contact
dermatitis or psoriasis) or visible rash present during physical examination
- Subjects, who according to the product label for midazolam, would be at increased risk
if dosed with midazolam
- Self-reported history or risk factors for QT prolongation or torsades de pointes,
congenital deafness, family history of sudden death, and family history of long QT
syndrome
- Any condition possibly affecting drug absorption (eg, gastrectomy)
- A positive urine drug test
- History of regular alcohol consumption exceeding 14 for female or 21 for male
drinks/week (1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard
liquor) within 6 months of screening
- Treatment with an investigational drug within 30 days (or as determined by the local
requirement) or 5 half-lives preceding the first dose of investigational product
(whichever is longer)
- Following at least 5 minutes of supine rest, screening supine systolic BP
>=140 mm Hg, or screening supine diastolic BP =90 mm Hg. Any criteria
met, BP should be repeated
- Screening supine 12-lead ECG demonstrating: QTcF >450 msec or QRS interval >120 msec.
If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated
- AST/SGOT or ALT/SGPT >=1.5 × ULN. Total bilirubin level >1× ULN; subjects with a hx of
Gilbert's syndrome must have direct bilirubin
elevated liver function tests (LFTs)
- History of tuberculosis (TB) (active or latent) or inadequately treated TB infection.
Positive QuantiFERON® - TB Gold test
- Any history of chronic infections, any history of recurrent infections, any history of
latent infections, or any acute infection within 2 weeks of baseline
- History of disseminated herpes zoster, or disseminated herpes simplex, or recurrent
localized dermatomal herpes zoster
- History of sensitivity to heparin or heparin-induced thrombocytopenia
- Pregnant or breastfeeding female; fertile male and WOCBP unwilling to use a highly
effective method of contraception through study duration and for at least 28 days
after the last dose
- Use of medications and dietary supplements within 7 days or 5 half-lives prior to
first dose, acetaminophen/paracetamol
hormonal methods of contraception
- Use of tobacco- or nicotine- containing products in excess of the equivalent of 5
cigarettes per day
- Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more
within 60 days prior to first dose of investigational product
- History of hypersensitivity to midazolam or any other bezodiazapine
- History of HIV, hepatitis B or C; positive testing for HIV, HepBsAg, HepBcAb or HCVAb.
As an exception, a positive HepBsAb as a result of subject vaccination is permissible
- Unwilling or unable to comply with the criteria in the Lifestyle Requirements section
of this protocol
- Investigator site staff members and their family members, site staff members otherwise
supervised by the investigator, or subjects who are Pfizer employees, including their
family members
- Other medical or psych condition including active suicidal ideation/ behavior or lab
abnormality that the investigator deems inappropriate for this study or may interfere
with study results
- Have any malignancies or have a history of malignancies with the exception of
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the
skin, or cervical carcinoma in situ
- Subjects at significant risk of suicidal or violent behavior