A PHASE 1, OPEN-LABEL, SINGLE-DOSE STUDY TO INVESTIGATE THE MASS BALANCE, METABOLISM AND EXCRETION OF [14C]-PF-07304814 IN HEALTHY PARTICIPANTS USING A 14C-MICROTRACER APPROACH
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Systematic Clearance (CL) for Plasma PF-07304814
研究概览
简要总结
This open-label, single dose study in approximately 5 healthy male and female (of non childbearing potential only) participants has been designed to characterize mass balance and further the understanding of human pharmacokinetics, metabolism, and excretion of PF 07304814 administered at a dose of 500 mg [14C] PF-07304814 containing approximately 420 nCi [14C] PF-07304814 as a constant-rate, continuous IV infusion over 24 hours
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female participants must be 18 to 55 years of age, inclusive, at the time of signing the ICD.
- •Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and ECGs.
- •Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- •BMI of 18 to 32 kg/m2; and a total body weight >50 kg (110 lb).
排除标准
- •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).
- •Positive test result for SARS-CoV-2 infection at the time of Screening or Day -
- •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.
- •Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer).
- •Participants who have received a COVID-19 vaccine within the past 2 weeks; and/or participants who are scheduled to receive a second COVID-19 vaccination dose during the in-clinical period of this study.
- •A positive urine drug test.
- •Total 14C radioactivity measured in plasma exceeding 11 mBq/mL at "Screening" .
- •Females who are breastfeeding.
- •History of tobacco or nicotine use within 3 months prior to dosing, or a positive cotinine at screening or Day -
- •Participants enrolled in a previous radionucleotide study or who have received radiotherapy within 12 months prior to screening or such that total radioactivity would exceed acceptable dosimetry (ie, occupational exposure of 5 rem per year).
- •13. Participants whose occupation requires exposure to radiation or monitoring of radiation exposure.
- •14. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.
研究组 & 干预措施
PF-07304814
PF-07304814 is an anti-viral, formulated for intravenous delivery
干预措施: PF-07304814 (Drug)
结局指标
主要结局
Systematic Clearance (CL) for Plasma PF-07304814
时间窗: 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Systemic clearance. This was determined by Dose/AUCinf (if data permit).
The Mean (SD) Amount of [14C] Recovered in Urine, as a Percent of the Total [14C] Dose Administered
时间窗: from pre-dose to 216h post the start of infusion
This is to confirm mass balance and characterize the routes of elimination of \[14C\]-PF-07304814 and drug related materials following 420 nCi/500 mg dose of \[14C\] PF-07304814.
The Mean (SD) Amount of [14C] Recovered in Feces, as a Percent of the Total [14C] Dose Administered
时间窗: from pre-dose to 216h post the start of infusion
This is to confirm mass balance and characterize the routes of elimination of \[14C\]-PF-07304814 and drug related materials following 420 nCi/500 mg dose of \[14C\] PF-07304814.
The Mean (SD) Percentage of [14C] Relative to the Administered Dose in Excreta (Urine + Feces)
时间窗: from pre-dose to 216h post the start of infusion
This is to confirm mass balance and characterize the routes of elimination of \[14C\]-PF-07304814 and drug related materials following 420 nCi/500 mg dose of \[14C\] PF-07304814.
Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for Plasma PF-07304814 and Plasma PF-00835231
时间窗: 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Area under the concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), using linear/log trapezoidal method.
Area Under the Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) for Plasma Total [14C]
时间窗: pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Area under the concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), using linear/log trapezoidal method.
Area Under the Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) for Plasma PF-00835231
时间窗: 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Area under the concentration-time profile from time zero extrapolated to infinite time. AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis (if data permit).
AUCinf for Plasma Total [14C]
时间窗: pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Area under the concentration-time profile from time zero extrapolated to infinite time. AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis (if data permit).
Maximum Observed Plasma Concentration (Cmax) for Plasma PF-07304814 and Plasma PF-00835231
时间窗: 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Maximum observed plasma concentration. This was observed directly from data.
Cmax for Plasma Total [14C]
时间窗: pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Maximum observed plasma concentration. This was observed directly from data.
Time for Cmax (Tmax) for Plasma PF-07304814 and Plasma PF-00835231
时间窗: pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Time for Cmax. This was observed directly from data as time of first occurrence.
Tmax for Plasma Total 14C
时间窗: pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Time for Cmax. This was observed directly from data as time of first occurrence.
Obsereved Plasma Concentration at 24 Hours (C24) for Plasma PF-07304814 and Plasma PF-00835231
时间窗: 24 hours post the start of infusion
Obsereved plasma concentration at 24 hours. This was observed directly from data.
C24 for Plasma Total [14C]
时间窗: 24hours post the start of infusion
Obsereved plasma concentration at 24 hours. This was observed directly from data.
Steady-state Volume of Distribution Following Intravenous Infusion (Vss) for Plasma PF-07304814
时间窗: 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Steady-state volume of distribution following intravenous infusion. This was determined by Vss=CL × \[MRT-(infusion time/2)\] where MRT is the Mean Residence Time and is calculated as AUMCinf (the area under the first moment curve from time 0 extrapolated to infinite time)/AUCinf (area under the concentration-time profile from time 0 extrapolated to infinite time), if data permit.
Terminal Elimination Half-life (t½) for Plasma PF-00835231
时间窗: 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Terminal elimination half-life. This was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve (if data permit).
t½ for Plasma Total [14C]
时间窗: pre-dose, 0.5h, 1h, 2h, 6h, 12h, 24h, 25h, 27h, 32h, 48h, 72h, 96h, 120h, 144h, 216h post the start of infusion
Terminal elimination half-life. This was determined by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve (if data permit).
次要结局
- Percentage of Total Radioactivity in Each Matrix (Plasma, Urine and Feces) of Metabolites of PF-07304814(Predose to maximum of Day 10)
- Number of Subjects With Treatment-emergent Adverse Events (TEAEs)(From first dose up to 28-35 days from administration of the dose of study intervention (maximum of 35 days))
- Number of Subjects With Vital Signs Data Meeting Categorical Summarization Criteria(from Screening (Day-42 to Day-2) to 216h or early termination/discontinuation)
- Number of Subjects With Laboratory Test Abnormalities (Without Regards to Baseline Abnormality)(From Screening (Day-42 to Day-2) to 216h or early termination/discontinuation)
- Number of Subjects With Electrocardiogram (ECG) Data Meeting Categorical Summarization Criteria(From Screening (Day-42 to Day-2) to 216h or early termination/discontinuation)