A Phase 1 Open-Label, Single-Dose, Two Cohort Crossover Study to Evaluate the Relative Bioavailability of a Test Formulation of PF-07799933 and the Effect of a High-Fat Meal on Plasma Pharmacokinetics of PF-07799933 and PF 07799544 Administered in Combination, and the Impact of a Proton Pump Inhibitor on the Plasma Pharmacokinetics of PF-07799933, in Healthy Participants.

Pfizer1 个研究点分布在 1 个国家目标入组 16 人开始时间: 2026年4月10日最近更新: 2026年7月9日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Pfizer
入组人数: 16
试验地点: 1
主要终点: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799933 Form 1 tablet when dosed in combination with PF-07799544 fasted

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to evaluate the relative bioavailability (rBA) of the Form 2 film-coated tablet of PF-07799933 intended for use in future studies compared to the current Form 1 tablet of PF-07799933 used in Phase 1 studies. Additionally this study will also evaluate the effect of a high-fat meal on the plasma pharmacokinetics (PK), i.e, the rBA compared to overnight fasting, of PF-07799933 and PF-07799544 following concurrent single-dose oral administration of Form 2 film-coated tablet formulation of PF-07799933 with PF-07799544. Finally, this study will also assess the impact of a proton pump inhibitor (a type of acid reducing agent) on PF-07799933 PK of the Form 2 film-coated tablet formulation. These data will be used to inform administration of PF-07799933 and PF-07799544 with food and acid reducing agents in future clinical trials.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Crossover
主要目的: Basic Science
盲法: None

入排标准

年龄范围: 18 Years 至 65 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•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)

排除标准

•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.

研究组 & 干预措施

PF-07799933 Form 1 Tablet Arm with PF-07799544 Fasted

Experimental

Cohort 1 Period 1: Participants receive PF-07799933 tablets in Combination With PF-07799544

干预措施: PF-07799933 tablets with PF-07799544 fasted (Drug)

PF-07799933 Form 2 Tablet Arm

Experimental

Cohort 2 Period 1: Participants receive PF-07799933 film-coated tablets

干预措施: PF-07799933 film-coated tablets fasted (Drug)

PF-07799933 Form 2 Film-Coated Tablet Arm with PF-07799544 Fasted

Experimental

Cohort 1 Period 2: Participants receive PF-07799933 film-coated tablets in Combination With PF-07799544

干预措施: PF-07799933 film-coated tablets with PF-07799544 fasted (Drug)

PF-07799933 Form 2 Film-Coated Tablet Arm with PF-07799544 under Fed Conditions

Experimental

Cohort 1 Period 3: Participants receive PF-07799933 film-coated tablets in Combination With PF-07799544 following a High-Fat Meal

干预措施: PF-07799933 film-coated tablets with PF-07799544 fed (Drug)

PF-07799933 Form 2 Tablet Arm following Rabeprazole Pretreatment

Experimental

Cohort 2 Period 1: Participants receive PF-07799933 film-coated tablets following rabeprazole treatment

干预措施: PF-07799933 film-coated tablets following rabeprazole pretreatment fasted (Drug)

结局指标

主要结局

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) for PF-07799933 Form 1 tablet when dosed in combination with PF-07799544 fasted