COVID-19: A MULTIPART, PHASE 1 STUDY WITH RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, SINGLE- AND MULTIPLE-DOSE ESCALATION TO EVALUATE THE SAFETY, TOLERABILITY AND PHARMACOKINETICS OF PF-07817883 AND OPTIONAL OPEN-LABEL, RANDOMIZED STUDY TO EVALUATE RELATIVE BIOAVAILABILITY AND FOOD EFFECT OF SOLID ORAL FORMULATION AND OPTIONAL OPEN-LABEL, NON-RANDOMIZED STUDY TO EVALUATE METABOLISM AND EXCRETION OF PF-07817883 AND OPTIONAL RANDOMIZED, OPEN-LABEL STUDY TO ASSESS THE EFFECT OF PF-07817883 ON PHARMACOKINETICS OF MIDAZOLAM 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
- 94
- 试验地点
- 2
- 主要终点
- Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this clinical trial is to learn if the study medicine (called PF-07817883) is safe and how it goes in and out of the body in healthy people. PF-07817883 is for the potential treatment of COVID-19. Participants will take PF-07817883 by mouth up to 2 times a day. This study may also evaluate how much PF-07817883 gets into the body when taken as pill. We may study if people's diets can affect this study medicine. We may also examine how PF-07817883 is processed and removed by the human body. Finally, we may look into if PF-07817883 has potential to interact with midazolam.
详细描述
Combined 6-part study. Part-1: Single Ascending dose Part-2: Multiple Ascending Dose Part-3: Relative bioavailability and food effect Part-4: Metabolism and Excretion Part-5: Drug-drug interaction with midazolam Part-6: Supratherapeutic exposure Part-1,2 and 6 are double blind, sponsor open and Part-3,4 and 5 are open label study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
PART-1, 2 and 6 are double-blind, sponsor-open while PART-3, 4 and 5 are open label
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female subjects between ages of 18-60 years. Male only in part-
- •Body Mass Index (BMI) of 17.5 to 30.5kg/m2; and a total body weight >50kg (110lbs). A body weight of >45 kg may be considered in selected cases.
- •Japanese subjects who have four Japanese biologic grandparents born in Japan
- •Chinese participants who were born in mainland China and both parents are of the Chinese descent.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing)
- •Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, intestinal resection).
- •Positive test result for SARS-CoV-2 infection at the time of screening or Day-
- •Have received COVID-19 vaccine within 7 days before screening or have received only one of the 2 required doses of COVID-19 vaccine
- •Use of tobacco or nicotine containing products in excess of the equivalents of 5 cigarettes per day or 2 chews of tobacco per day
- •Use of prescription or nonprescription drugs and dietary and herbal supplements within 28 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
研究组 & 干预措施
PF-07817883 Dose 1 in PART-1
干预措施: PF-07817883 (Drug)
PF-07817883 Dose 2 in PART-1
干预措施: PF-07817883 (Drug)
PF-07817883 Dose 3 in PART-1
干预措施: PF-07817883 (Drug)
PF-07817883 Dose 4 in PART-1
干预措施: PF-07817883 (Drug)
PF-07817883 Dose 5 in PART-1
Optional dose levels
干预措施: PF-07817883 (Drug)
PF-07817883 Dose 6 in PART-1
Optional dose levels
干预措施: PF-07817883 (Drug)
Placebo in PART-1
A single dose of placebo
干预措施: Placebo (Drug)
PF-07817883 DR1 in PART-2
DR=Dosing regimen; twice a day
干预措施: PF-07817883 (Drug)
PF-07817883 DR2 in PART-2
干预措施: PF-07817883 (Drug)
PF-07817883 DR3 in PART-2
Optional dosing regimen
干预措施: PF-07817883 (Drug)
PF-07817883 DR4 in PART-2
Optional dosing regimen
干预措施: PF-07817883 (Drug)
PF-07817883 in Japanese in PART-2
Optional dosing regimen to be studied in Japanese population
干预措施: PF-07817883 (Drug)
PF-07817883 in Chinese in PART-2
Optional dosing regimen to be studied in Chinese population
干预措施: PF-07817883 (Drug)
Placebo in PART-2
干预措施: Placebo (Drug)
PF-07817883 Suspension Fasted in PART-3
PART-3 is optional
干预措施: PF-07817883 (Drug)
PF-07817883 FORM-1 Fasted in PART-3
First solid oral formulation (FORM1)
干预措施: PF-07817883 (Drug)
PF-07817883 FORM-2 Fasted in PART-3
Second solid oral formulations (FORM-2) is optional
干预措施: PF-07817883 (Drug)
PF-07817883 FORM-1 Fed in PART-3
干预措施: PF-07817883 (Drug)
PF-07817883 FORM-2 Fed in PART-3
干预措施: PF-07817883 (Drug)
PF-07817883 in PART-4
PART-4 is optional
干预措施: PF-07817883 (Drug)
Midazolam 5 mg in PART-5
Single dose of 5 mg alone
干预措施: Midazolam (Drug)
Midazolam 5 mg with PF-07817883 in PART-5
Single dose of 5 mg on Day 10 with multiple doses (twice a day) of PF-07817883
干预措施: PF-07817883 (Drug)
Midazolam 5 mg with PF-07817883 in PART-5
Single dose of 5 mg on Day 10 with multiple doses (twice a day) of PF-07817883
干预措施: Midazolam (Drug)
PF-07817883 in PART-6
A single dose at supratherapeutic exposure administered as divided doses (1h apart)
干预措施: PF-07817883 (Drug)
Placebo in PART-6
A single dose of placebo administered as divided doses (1h apart)
干预措施: Placebo (Drug)
Moxifloxacin 400 mg in PART-6 (open label)
Moxifloxacin 400 mg at 0h followed by placebo at 1h
干预措施: Placebo (Drug)
Moxifloxacin 400 mg in PART-6 (open label)
Moxifloxacin 400 mg at 0h followed by placebo at 1h
干预措施: Moxifloxacin (Drug)
结局指标
主要结局
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 days)
An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.
Part 1: Number of Participants With Laboratory Test Abnormalities
时间窗: From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 days)
Laboratory parameters included: (lymphocytes less than (\<) 0.8\*lower limit of normal \[LLN\] \[10\^3 per millimeter cube {mm3}\], lymphocytes/leukocytes \<0.8\*LLN \[percentage {%}\], neutrophils \<0.8\*LLN \[10\^3/mm3\], neutrophils/leukocytes \<0.8\*LLN \[%\], monocytes/leukocytes greater than (\>) 1.2\*upper limit of normal \[ULN\] \[%\], partial thromboplastin time \>1.1\*ULN \[seconds\]), chemistry (bicarbonate \<0.9\*LLN \[milliequivalents per liter {mEq/L}\], creatine kinase \>2.0\*ULN \[units per liter {U/L}\], lipase \>1.5\*ULN \[U/L\]), and urinalysis (urine hemoglobin greater than or equal to \[\>=\] 1, leukocyte esterase \>=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.
Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria
时间窗: Up to Day 2 of each period
Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value less than (\<) 90 millimeter of mercury (mmHg), change greater than or equal to (\>=) 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 beats per minute (bpm), value \> 120 bpm.
Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities
时间窗: Up to Day 2 of each period
Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.
Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
时间窗: From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 days)
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.
Part 4: Percentage of Total Dose Administered Recovered in Urine
时间窗: Up to 144 hours post-dose
The percentage of total dose administered recovered in urine was reported in this outcome measure.
Part 2: Number of Participants With Laboratory Test Abnormalities
时间窗: From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 days)
Laboratory parameters included: hematology (lymphocytes/leukocytes \>1.2\*ULN \[%\], neutrophils \<0.8\*LLN \[10\^3/mm3\], neutrophils/leukocytes \<0.8\*LLN \[%\], monocytes/leukocytes \>1.2\*ULN \[%\]), chemistry (urate \>1.2\*ULN \[milligrams per deciliter\] {mg/dL}), and urinalysis (ketones \>=1, urine hemoglobin \>=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.
Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria
时间窗: Up to Day 12
Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 bpm, value \> 120 bpm. 4. Number of participants with vital signs meeting any of the pre-defined criteria is reported in this outcome measure.
Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities
时间窗: Up to Day 12
Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.
Part 3:Ratio Based on Area Under Plasma Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) and Area Under Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) of Oral Formulation and Suspension
时间窗: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Data for AUClast and AUCinf are reported in the descriptive section. AUClast was calculated by the linear/log trapezoidal method. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis. Ratio based on AUClast and AUCinf of oral formulation and suspension were reported in statistical analysis.
Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and Suspension
时间窗: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Data for Cmax are reported in the descriptive section. Ratio based on Cmax of oral formulation and suspension were reported in statistical analysis.
Part 4: Percentage of Total Dose Administered Recovered in Feces
时间窗: Up to 144 hours post-dose
The percentage of total dose administered recovered in feces was reported in this outcome measure.
Part 4: Percentage of Total Dose Administered Recovered in Urine and Feces
时间窗: Up to 144 hours post-dose
The percentage of total dose administered recovered in urine and feces was reported in this outcome measure.
Part 5: Maximum Observed Concentration (Cmax) of Midazolam
时间窗: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm
Cmax of midazolam was reported in this outcome measure.
Part 5: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Midazolam
时间窗: Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm
AUCinf of midazolam was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.
Part 6: Number of Participants With TEAEs
时间窗: From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 days)
An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.
Part 6: Number of Participants With Laboratory Test Abnormalities
时间窗: From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 days)
Laboratory parameters included: hematology (lymphocytes \<0.6\*LLN \[10\^3/mm3\], lymphocytes/leukocytes \>1.2\*ULN \[%\], neutrophils \<0.8\*LLN \[10\^3/mm3\], neutrophils/leukocytes \<0.8\*LLN \[%\], basophils/leukocytes \>1.2\*ULN \[%\], eosinophils/leukocytes \>1.2\*ULN \[%\], monocytes/leukocytes \>1.2\*ULN \[%\], partial thromboplastin time \>1.1\*ULN \[seconds\], prothrombin time \>1.1\*ULN \[seconds\]), chemistry (bicarbonate \<0.9\*LLN \[mEq/L\], creatine kinase \> 2.0\*ULN \[U/L\], lipase \> 1.5\*ULN \[U/L\], urobilinogen \>=1 \[ehrlich units/deciliter\] {EU/dL}) and urinalysis (urine hemoglobin \>=1, leukocyte esterase \>=1, ketones \>=1, bacteria \>20 \[per low power field\] {/lpf}). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.
Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria
时间窗: Up to Day 6 of each period
Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value \< 90 mmHg, change \>= 30 mmHg increase, change \>= 30 mmHg decrease; DBP: value \< 50 mmHg, change \>= 20 mmHg increase, change \>= 20 mmHg decrease; PR: value \< 40 bpm, value \> 120 bpm.
Part 6: Number of Participants According to Categorization of ECG Data
时间窗: Up to Day 6 of each period
Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured QTcF interval, aggregate 450 milliseconds (msec) \< value \<= 480 msec and QTcF interval, aggregate 30 msec \< change \<= 60 msec. Number of participants with abnormalities in ECG were reported in this outcome measure.
次要结局
- Part 1: Maximum Observed Concentration (Cmax) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 1: Time for Cmax (Tmax) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 1: Terminal Half-Life (t1/2) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 1: Apparent Clearance (CL/F) of PF-07817883(Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10(Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10(Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 2: Area Under the Plasma Concentration-Time Profile From Time 0 to Time Tau, the Dosing Interval (AUCtau) of PF-07817883 on Days 1, 5 and 10(Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose))
- Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10(12 hours on Day 5 and Day 10)
- Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10(Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10(Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose))
- Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10(Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose))
- Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10(Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose))
- Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10(Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10(Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10(Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 2: Apparent Volume of Distribution (Vz/F) of PF-07817883 on Day 10(Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 2: Terminal Half-Life (t1/2) of PF-07817883 on Day 10(Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 2: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of PF-07817883 on Day 10(Day 10 (0 to 12 hours))
- Part 2: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of PF-07817883 on Day 10(Day 10 (0 to 12 hours))
- Part 2: Renal Clearance (CLr) of PF-07817883 on Day 10(Day 10 (0 to 12 hours))
- Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Tablet Formulation Under Fed Condition and Fasted Condition(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 3: Time for Cmax (Tmax) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 3: Maximum Observed Concentration (Cmax) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 3: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 3: Terminal Half-Life (t1/2) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 3: Apparent Clearance (CL/F) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 3: Apparent Volume of Distribution (Vz/F) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose))
- Part 3: Number of Participants With TEAEs(From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 49 days))
- Part 3: Number of Participants With Laboratory Test Abnormalities(From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 49 days))
- Part 3: Number of Participants With Vital Signs Meeting Pre-Defined Criteria(Up to Day 3 of each period)
- Part 3: Number of Participants With ECG Abnormalities(Up to Day 3 of each period)
- Part 4: Time for Cmax (Tmax) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 4: Maximum Observed Concentration (Cmax) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 4: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 4: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 4: Terminal Half-Life (t1/2) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 4: Apparent Clearance (CL/F) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 4: Apparent Volume of Distribution (Vz/F) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose))
- Part 4: Number of Participants With TEAEs(From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 47 days))
- Part 4: Number of Participants With Laboratory Test Abnormalities(From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 47 days))
- Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria(Up to Day 11)
- Part 4: Number of Participants With ECG Abnormalities(Up to Day 11)
- Part 5: Number of Participants With TEAEs(From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days))
- Part 5: Number of Participants With Laboratory Test Abnormalities(From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days))
- Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria(From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days))
- Part 5: Number of Participants With ECG Abnormalities(From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days))
- Part 5: Time for Cmax (Tmax) of Midazolam(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm)
- Part 5: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm)
- Part 5: Terminal Half-Life (t1/2) of Midazolam(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm)
- Part 5: Apparent Clearance (CL/F) of Midazolam(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm)
- Part 5: Apparent Volume of Distribution (Vz/F) of Midazolam(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm)
- Part 6: Maximum Observed Concentration (Cmax) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose))
- Part 6: Time for Cmax (Tmax) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose))
- Part 6: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose))
- Part 6: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose))
- Part 6: Terminal Half-Life (t1/2) of PF-07817883(Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose))