A Study to Determine the Effects of PF-04965842 on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Subjects
Condition: Healthy Females
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a Phase 1, randomized, 2 way crossover, open-label study of the effect of
      multiple-dose PF 04965842 on single-dose OC PK in healthy female subjects. Subjects will be
      randomized to 1 of 2 treatment sequences. A total of 16 healthy female subjects (8 in each
      treatment sequence) will be enrolled in the study. Each treatment sequence will consist of 2
      periods.
    

Detailed description: 
      In Treatment Sequence 1, Period 1 Day 1, subjects will be dosed with a single administration
      of OC in the form of 1 PORTIA (ethyinyl estradiol [EE] and levonorgestrel [LN]) or equivalent
      tablet, orally. OC (EE and LN) PK will then be assessed at pre dose and over 48 hours after
      OC dosing. Period 1 will be immediately followed by Period 2 with no washout. The 48 hours
      post-OC dose PK sample for Period 1 must be collected prior to receiving the first dose of PF
      04965842 in Period 2. In Period 2, subjects will be dosed with 200 mg PF 04965842 PO QD for 9
      days followed by administration of a single dose of OC oral tablet immediately after
      administration of a 200 mg dose of PF-04965842 on the morning of Day 10. OC PK in Period 2
      will be assessed at pre dose and over 48 hours after OC dosing. Dosing with 200 mg PF
      04965842 PO QD will continue until Day 11.

      In Treatment Sequence 2, Period 1, subjects will be dosed with 200 mg PF 04965842 PO QD for 9
      days followed by administration of a single dose of OC oral tablet immediately after
      administration of a 200 mg dose of PF-04965842 on the morning of Day 10. OC PK will be
      assessed at pre dose and over 48 hours following OC dosing. Dosing with 200 mg PF 04965842 PO
      QD will continue until Day 11. Subjects will then undergo a washout period of at least 10
      days (Day -1 of Period 2 starts 10 days after Day 12 of Period 1). In Period 2 subjects will
      be dosed with a single OC administration on Day 1. OC PK will then be assessed at pre dose
      and over 48 hours after OC dose.
    

Intervention name(s): PF-04965842; Ethinyl estradiol (EE) and levonorgestrel (LN)
Intervention type(s): Drug; Drug
Intervention description(s): Orally bioavailable small molecule that selectively inhibits JAK 1 by blocking the adenosine triphosphate (ATP) binding site.; Single dose of Oral tablet containing 30 ug EE and 150 ug of LN
Other intervention name(s): JAK 1 inhibitor; Oral contraceptive
Intervention MeSH terms: Levonorgestrel; Ethinyl Estradiol; Contraceptive Agents; Contraceptives, Oral; Estradiol; Abrocitinib
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Natural log transformed AUCinf, AUClast, and Cmax of EE and LN will be analyzed separately using a mixed effect model with sequence, period and treatment as fixed effects and subject within sequence as a random effect. Estimates of the adjusted 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% CIs for the ratios. OC (EE and LN) alone will be the Reference treatment, while the OC (EE and LN) coadministered with PF 04965842 will be the Test treatment.
The absent of an effect of PF 04965842 on OC (EE and LN) will be concluded if the lower bound of 90% confidence interval for the ratio of adjusted geometric mean for AUCinf is ≥80%.
Masking: None (Open Label)
Primary purpose: Other
Keywords: PF-04965842