Relative Bioavailability and Impact of Rabeprazole for PF-07799933, Food-Effect for PF-07799933 and PF-07799544

This is a Phase 1, open-label, randomized, single-dose, 2-cohort study: a three period two sequence crossover (Relative Bioavailability and Food Effect) cohort in healthy adult participants, and a two-period single sequence cohort (Proton Pump Inhibitor) in healthy adult participants. Cohort 1 of this study, which has 3 periods, will evaluate the impact of the Form 2 film-coated tablet of PF-07799933 (test formulation) compared to the Form 1 tablet of PF-07799933 (reference formulation) used in the C4901001 and C4761001 Phase 1 studies (Period 1 and Period 2). This cohort (Cohort 1) will also evaluate the effect of a high fat meal on plasma pharmacokinetics (ie, the relative bioavailability compared to overnight fasting) of the Form 2 film-coated tablet of PF-07799933 and of PF-07799544 following concurrent single-dose administrations of 300 mg of PF 07799933 and the optimized dose identified from an ongoing clinical study (either 7.5 or 12 mg) of PF 07799544 to healthy adult participants (Period 3). Cohort 2, which has two periods, will evaluate the plasma pharmacokinetics of PF-07799933 before (Period 1) and after administration of the proton pump inhibitor rabeprazole (20 mg BID for 3 days and once in the morning for the last dose [seven total doses]) (Period 2). Cohort 2 will be conducted using the Form 2 film-coated tablet of PF-07799933 in both periods.

Inclusion criteria

• Female participants of non-childbearing potential and male participants 18 to 65 years of age (or the minimum age of consent in accordance with local regulations) at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, vital signs and ECGs.
• BMI of 16-32 kg/m2; and a total body weight >50 kg (110 lb)

Exclusion criteria

• Evidence or history of clinically significant uveitis, hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, chronic diarrhea, - inflammatory bowel disease).
• History of HIV infection, hepatitis B, or hepatitis C
• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (eg,glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease (including evidence of macular degeneration); blurred vision.
• Any evidence of active bacterial, fungal, or viral infection
• Participants who have undergone major surgery ≤ 2 weeks prior to starting study treatment
• Participants with known or suspected hypersensitivity to active ingredient/excipients
• Any medical or psychiatric condition including any active suicidal ideation in the past year or suicidal behavior in the past 5 years or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• 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 study intervention. Prior or concomitant use of proton pump inhibitors within 7 days prior to first dose of study intervention is prohibited. Also prohibited is prior or concomitant use of any medications or substances that are:
• For Cohort 1: strong or moderate inducers of CYP3A4/5, CYP2C9, or UGT2B7 within 28 days or 5 half-lives plus 10 days prior to first dose of study intervention, and strong or moderate inhibitors of CYP3A4/5, CYP2C9, UGT1A9 or UGT2B7 within 5 half-lives or 10 days (whichever is longer) prior to first dose of study intervention.
• For Cohort 2: strong or moderate inducers of UGT2B7 within 28 days or 5 half-lives plus 10 days prior to first dose of study intervention, and strong or moderate inhibitors of UGT2B7 within 5 half-lives or 10 days (whichever is longer) prior to first dose of study intervention.
• Current use of concomitant medication(s) or unwillingness or inability to use a required concomitant medication(s).
• Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).
• A positive urine drug test. A single repeat for positive drug screen may be allowed.
• Use of tobacco or nicotine containing products within 3 months of screening or a positive urine cotinine test (ie, active smokers and those who currently use nicotine-containing products are excluded from participation in this study).
• Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants <60 years; and ≥150/90 mm Hg for participants ≥60 years old, following at least 5 minutes of supine rest. If systolic BP is ≥ 140 or 150 mm Hg (based on age) or diastolic ≥90 mm Hg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
• An eGFR < 60 (units of mL/min/1.73 m²) as determined by the CKD-EPI equation
• Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
• Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:

ALT, AST, Bilirubin ≥1.5× ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN, Hemoglobin ≤ 11 g/dL ANC ≤ 1.5 × 109/L, Platelets ≤ 150,000/mm3/.

• History of alcohol abuse or repeated binge drinking and/or any other illicit drug use or dependence within 6 months of screening.