A Study to Determine the Effects of PF-04965842 on Midazolam PK in Healthy Volunteers
Condition: Phase 1
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase 1, randomized, 2-way crossover, multiple dose, open label study of the effect
      of PF-04965842 on midazolam PK in healthy subjects. The study will demonstrate the effect of
      multiple dose PF-04965842 on the pharmacokinetics of a single, oral dose of midazolam in
      healthy subjects.
    

Detailed description: 
      Subjects will be randomized to 1 of 2 treatment sequences as described below. A total of 24
      healthy male and/or female subjects will be enrolled in the study so that 12 subjects will be
      enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods in a
      single fixed sequence. Subjects will be screened within 28 days of the first dose of study
      medication. Subjects will report to the clinical research unit (CRU) the day prior to (or Day
      -1) Day 1 dosing in Period 1 for both treatment sequences. In Sequence 1 subjects will remain
      in the CRU for a total of 11 days and 10 nights (including Period 1 and Period 2). In
      Sequence 2, Period 1, subjects will remain in the CRU for 9 days and 8 nights. In Sequence 2,
      Period 2, subjects will remain in the CRU for 3 days and 2 nights. In Sequence 1, Period 1,
      subjects will be dosed with a single administration of midazolam 2 mg oral solution on Day 1.
      Midazolam PK will then be assessed over the next 24 hours (hr). Period 1 will be immediately
      followed by Period 2 with no washout, in which subjects will be dosed with 200 mg PF-04965842
      orally once daily (QD) for 7 days. Midazolam 2 mg oral solution will be administered on the
      morning of Day 2 and Day 7 within 5 minutes after PF-04965842 dosing. Midazolam PK will be
      assessed for 24 hr following dosing.In Sequence 2, Period 1, subjects will be dosed with 200
      mg PF-04965842 orally QD for 7 days. Midazolam 2 mg oral solution will be administered on the
      morning of Day 2 and Day 7 within 5 minutes after PF-04965842 dosing. Midazolam PK will be
      assessed for 24 hr following dosing. Subjects will then undergo a washout period of at least
      7 days. In Period 2 subjects will be dosed with a single administration of midazolam 2 mg
      oral solution on Day 1. Midazolam PK will then be assessed over the next 24 hr.
    

Intervention name(s): PF-04965842; Midazolam
Intervention type(s): Drug; Drug
Intervention description(s): orally bioavailable small molecule that selectively inhibits JAK1 by blocking the adenosine triphosphate (ATP) binding site.; substrate which undergoes extensive metabolism by CYP3A4 and CYP3A5 and acts as a sensitive probe for evaluating drug interaction with respect to these isoenzymes
Other intervention name(s): JAK1 Inhibitor
Intervention MeSH terms: Midazolam; Abrocitinib
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Natural log transformed area under the curve from zero to infinity, area under the plasma concentration-time curve from 0 to the time of last measurement and max plasma concentration of midazolam will be analyzed using a mixed effect model with sequence, period and treatment as fixed effects and subject within sequence as a random effect. Estimates of the adj mean differences (Test-Reference) and corresponding 90% CIs will be obtained from the model. The adjusted mean differences and 90% CIs for the differences will be exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% confidence intervals for the ratios. Midazolam alone will be the Reference treatment, while the midazolam co-administered with PF-04965842 will be the Test treatment. The lack of an effect of PF-04965842 on midazolam PK will be concluded if the 90% CI for the ratio of adjusted geometric mean for AUCinf falls wholly within acceptance region (80%, 125%).
Masking: None (Open Label)
Primary purpose: Other
Keywords: PF-04965842