A Study to Estimate the Effect of Multiple Dose Abrocitinib on Caffeine, Efavirenz, and Omeprazole in Healthy Participants

Inclusion Criteria

• Participants must be ≥18 years of age at the time of signing the Informed consent document (ICD).
• Male and female participants who are healthy as determined by medical evaluation including a detailed medical history, complete physical examination, laboratory tests, and cardiovascular tests.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Body mass index (BMI) of 17.5 to 32 kg/m2; and a total body weight >50 kg (110 lb).
• Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria

• Evidence or history of clinically significant hematological, renal, endocrine, neurological diseases, or other systems diseases, allergic diseases including drug allergies but excluding untreated asymptomatic seasonal allergies at the time of dosing
• Subjects with moderate to severe gastroesophageal reflux disease (GERD) symptoms, or any condition affecting drug absorption e.g. gastrectomy, cholecystectomy
• History of human immunodeficiency virus (HIV) infection, positive test for HIV, hepatitis B, hepatitis C, positive test for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCVAb). Subjects previously vaccinated for hepatitis B may be allowed. However, subjects vaccinated with vaccines having live or attenuated components within 6 weeks of the first dose of study drug, or expecting to be vaccinated during the course of the trial are excluded.
• Any psychiatric condition including recent or active suicidal ideation or behavior, other psychiatric conditions that may increase the risk of study participation, or, in the investigator's judgement, make the subject inappropriate for the study.
• Evidence or history of clinically significant dermatological conditions, e.g. atopic dermatitis (AD) or psoriasis, or visible rash present during physical examination, history of disseminated herpes zoster or disseminated herpes simplex, or localized dermatomal herpes zoster.
• History of chronic infections, recurrent infections or latent infections, e.g. tuberculosis (TB); Positive QuantiFERONE® TB GOLD test, any acute infection within 2-weeks of baseline (Day-1).
• Malignancies or history of malignancies except for adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ.
• History of hypersensitivity, intolerance, or allergic reaction associated with prior exposure to caffeine, omeprazole, efavirenz and abrocitinib or any of their excipients.
• Subjects who may be at increased risk if dosed with efavirenz, including severe hepatic impairment (Child Pugh Class C), or a history of seizures.
• Use of prescription or non-prescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study drug; herbal supplements and hormonal contraceptives and hormone replacement therapy (HRT) must be discontinued at least 28 days prior to the first dose of the investigational product; Depo-Provera® must be discontinued at least 6 months prior to dosing with investigational product.
• Systemic therapy with any of the medicines that are moderate or strong cytochrome P450 (CYP)1A2, CYP2B6, or CYP2C19 inhibitors within 28 days or 5 half-lives (whichever is longer), or moderate or strong CYP1A2, CYP2B6 or CYP2C19 inducers within 28 days or 5-half-lives (whichever is longer) prior to the first dose.
• Previous administration with any investigational drug within 30 days (or as determined by local requirements), or 5-half-lives preceding the first dose of study drug intervention used in this study (whichever is longer).
• Smokers and/or subjects who used nicotine-based products within three months prior to the first dose of the investigational product.