Study of PF 04965842 Effect on MATE1/2K Activity in Healthy Participants
Condition: Healthy
Intervention: Metformin; PF-04965842
Intervention description: Commercially available metformin (GLUCOPHAGE®) as 500 mg tablets.; PF 04965842 100 mg tablets
Intervention MeSH terms: Metformin; Abrocitinib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF 04965842 on metformin PK in healthy adult participants. The effect of PF 04965842 on N1 methylnicotinamide (NMN) PK and its correlation to the effect on metformin PK will also be assessed.
A total of approximately 12 healthy male and/or female participants will be enrolled in the study so that approximately 6 participants will be enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods. Participants who discontinue from the study may be replaced at the sponsor's discretion. The replacement participant will receive the same treatment sequence as the participant who discontinued.
Participants will be screened within 28 days of the first dose of investigational product. Participants will report to the clinical research unit (CRU) the day prior to Day 1 (ie Day -1) dosing in Period 1 for both treatment sequences. In both sequences, participants will remain in the CRU for
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Phase 1; Metformin; Atopic dermatitis

Summary:

      This is a Phase 1, randomized, 2 way crossover, open label study of the effect of PF-04965842
      on metformin (a probe for MATE1/2K activity) PK in healthy adult participants. The effect of
      PF-04965842 on N1-methylnicotinamide (NMN; an endogenous biomarker for MATE1/2K) PK and its
      correlation to the effect on metformin PK will also be assessed. Participants will be
      randomized to 1 of 2 treatment sequences as described below. A total of 12 healthy male
      and/or female participants will be enrolled in the study so that 6 participants will be
      enrolled in each treatment sequence. Each treatment sequence will consist of 2 periods.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female participants who are overtly 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.

          -  Female participants who are of child bearing potential must not be intending to become
             pregnant, currently pregnant, or lactating.

          -  Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).

          -  Capable of giving signed informed consent.

        Exclusion Criteria:

          -  Evidence or history of clinically significant hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or
             allergic disease.

          -  Any condition possibly affecting drug absorption (eg, gastrectomy).

          -  History of human immunodeficiency virus (HIV), hepatitis B virus, or hepatitis C virus
             infection; positive testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis
             B core antibody (HepBcAb), or hepatitis C virus antibody (HCVAb).

          -  Other acute or chronic medical or psychiatric condition including recent (within the
             past year).

          -  Evidence or history of clinically significant dermatological condition (eg, atopic
             dermatitis or psoriasis) or visible rash present during physical examination.

          -  Clinically relevant history of lactic acidosis.

          -  Use of prescription or nonprescription drugs and dietary and herbal supplements within
             7 days or 5 half lives (whichever is longer) prior to the first dose of
             investigational product.

          -  A positive urine drug test.

          -  Selected laboratory abnormalities.

          -  History of regular alcohol consumption exceeding 14 drinks/week for female
             participants or 21 drinks/week for male participants (1 drink = 5 ounces [150 mL] of
             wine or 12 ounces [360 mL] of beer or 1.5 ounces [45 mL] of hard liquor) within 6
             months before screening.

          -  Known relevant history of elevated liver function tests (LFTs).

          -  History of tuberculosis (TB) (active or latent)

          -  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.