A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE DOSE, CROSSOVER STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF NIRMATRELVIR (PF-07321332) /RITONAVIR ORAL POWDER IN 3 DIFFERENT FOOD DELIVERY VEHICLES RELATIVE TO THE NIRMATRELVIR (PF-07321332) /RITONAVIR COMMERCIAL TABLETS UNDER FASTED CONDITIONS, AND THE EFFECT OF FOOD ON RELATIVE BIOAVAILABILITY OF NIRMATRELVIR (PF-07321332) /RITONAVIR ORAL POWDER IN HEALTHY ADULT PARTICIPANTS
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
- Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
研究概览
简要总结
The purpose of this study is to estimate the relative bioavailability (rBA) of nirmatrelvir/ritonavir oral powder in 3 different food vehicles relative to the Paxlovid® tablets under fasted condition in healthy adult participants, and to estimate the effect of food on the rBA of the nirmatrelvir/ritonavir oral powder formulation. The study will also assess the safety, tolerability, and palatability of nirmatrelvir/ritonavir oral powder 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: Nirmatrelvir/ritonavir
Nirmatrelvir and ritonavir tablets
干预措施: Nirmatrelvir/ ritonavir (Drug)
Treatment B: Nirmatrelvir/ ritonavir
Nirmatrelvir/ritonavir with water
干预措施: Nirmatrelvir/ritonavir (Drug)
Treatment C: Nirmatrelvir/ ritonavir
Nirmatrelvir/ ritonavir with infant formula
干预措施: Nirmatrelvir/ritonavir (Drug)
Treatment D: Nirmatrelvir/ ritonavir
Nirmatrelvir/ ritonavir with vanilla pudding
干预措施: Nirmatrelvir/ritonavir (Drug)
Treatment E: Nirmatrelvir/ ritonavir
Nirmatrelvir/ ritonavir with food and vanilla pudding
干预措施: Nirmatrelvir/ritonavir (Drug)
结局指标
主要结局
Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
Cmax was defined maximum observed concentration. Cmax for nirmatrelvir was observed directly from data.
AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for ritonavir was calculated by linear/log trapezoidal method.
AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. 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; AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. AUCinf for ritonavir 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; AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.
AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for nirmatrelvir was calculated by linear/log trapezoidal method.
Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles
时间窗: 0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
Cmax was defined maximum observed concentration. Cmax for ritonavir was observed directly from data.
次要结局
- Number of Participants With Clinically Significant Vital Signs(Baseline up to Day 4 of Period 5 (approximately 20 days).)
- Taste Assessment of Bitterness After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles(1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.)
- Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions(0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.)
- AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions(0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.)
- AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions(0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.)
- AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions(0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.)
- Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Values(Baseline up to Day 4 of Period 5 (approximately 20 days).)
- Taste Assessment of Throat Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles(1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.)
- AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions(0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.)
- Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions(0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.)
- Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs)(Baseline up to 28 days after last dose of study intervention (ie, up to 48 days).)
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)(Baseline up to Day 4 of Period 5 (approximately 20 days))
- Number of Participants With Clinically Significant Physical Examination (PE) Values(Screening, Baseline up to Day 4 of Period 5 (approximately 20 days).)
- Taste Assessment of Tongue/Mouth Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles(1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.)
- Taste Assessment of Mouth Feel After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles(1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.)
- Taste Assessment of Overall Liking After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles(1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.)