A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE-DOSE, CROSSOVER STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF PF-07321332 FOLLOWING ORAL ADMINISTRATION OF 4 DIFFERENT FORMULATIONS RELATIVE TO THE COMMERCIAL TABLET FORMULATION IN HEALTHY ADULT PARTICIPANTS UNDER FASTED CONDITIONS
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir
研究概览
简要总结
The purpose of this study is to estimate the relative bioavailability of PF-07321332 in different formulations in healthy adult participants.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination (PE), laboratory tests, vital signs and standard 12 lead ECGs.
- •Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
- •Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
排除标准
- •Positive test result for SARS-CoV-2 infection at the time of Screening or Day -
- •Evidence or history of clinically significant 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).
- •Clinically relevant abnormalities requiring treatment (eg, acute myocardial infarction, unstable ischemic conditions, evidence of ventricular dysfunction, serious tachy or brady arrhythmias) or indicating serious underlying heart disease (eg, prolonged PR interval, cardiomyopathy, heart failure greater than New York Heart Association (NYHA) 1, underlying structural heart disease, Wolff Parkinson-White syndrome).
- •Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
- •History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), or hepatitis B surface antibody (HCVAb). Hepatitis B vaccination is allowed.
- •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.
- •Participant who have received a COVID-19 vaccine within 7 days before screening or admission, or who are to be vaccinated with a COVID-19 vaccine at any time during the study confinement period.
- •A positive urine drug test.
研究组 & 干预措施
Treatment A: PF-0732133/ritonavir
PF-07321332 ritonavir
干预措施: PF-07321332/ritonavir (Drug)
Treatment B: PF-07321332/ritonavir
PF-07321332 ritonavir
干预措施: PF-07321332/ritonavir (Drug)
Treatment C: PF-07321332/ritonavir
PF-07321332 ritonavir
干预措施: PF-07321332/ritonavir (Drug)
Treatment D: PF-07321332/ritonavir
PF-07321332 ritonavir
干预措施: PF-07321332/ritonavir (Drug)
Treatment E: PF-07321332
PF-07321332
干预措施: PF-07321332 (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir
时间窗: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
AUCinf for nirmatrelvir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. Natural log-transformed AUCinf for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUCinf for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.
Maximum Plasma Concentration (Cmax) of Nirmatrelvir
时间窗: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
Cmax for nirmatrelvir was observed directly from data. Natural log-transformed Cmax for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed Cmax for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir
时间窗: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
AUClast for nirmatrelvir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUClast for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.
次要结局
- Number of Participants With Vital Signs Abnormalities(Screening (D28-D2), D1 of Period 1 (before 1st dose), D1 hr 0,2,and 6 of each period, and D4 of Period 5 (4 days after the last dose on study discharge day). Each treatment Period was 4 days long (D1-D4) with a minimum 4 days washout between each period)
- Number of Participants With ECG Abnormalities(Screening (from D-28 to D-2), D1, hr0 of Period 1 (before 1st dose) and D4 of Period 5 (4 days after last dose on study discharge day). Each treatment period was 4 days long (D1 to D4) with a minimum of 4 days washout between each period)
- Number of Participants With Physical Examination Abnormalities(Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose. Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period)
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Baseline up to 35 days after last dose of study intervention (up to 12 weeks))
- Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)(Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose) and Day4 of Period 5 (4 days after the last dose on study discharge day). Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period)