A Study to Learn Safety and Blood Levels of PF-07817883 in Healthy People

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-07817883
* Drug: Placebo
* Drug: Midazolam
* Drug: Moxifloxacin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects between ages of 18-60 years. Male only in part-4. 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. Exclusion Criteria: 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-1. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: PART-1 and -2 are a randomized, double-blind, sponsor-open, placebo-controlled trial to evaluate safety, tolerability and PK of single and multiple escalating oral doses of PF 07817883 in healthy adult participants, respectively. PART-1 is crossover while PART-2 is parallel cohort study design. PART-2 of the study may also evaluate the safety, tolerability and PK in Japanese and Chinese participants. PART-3 is a randomized, open-label, cross-over, study to evaluate relative bioavailability and food effect of up to 2 new PF 07817883 oral formulations. PART-4 is an open label, non-randomized, single period cohort to evaluate the metabolism and excretion of PF 07817883. PART-5 is an open-label, randomized, cross-over cohort to evaluate the effect of steady state PF-07817883 on PK of midazolam in healthy participants. PART-6 is a sponsor-open, randomized, 3-treatment, 3-period, cross over study to evaluate safety, tolerability, and PK of PF 07817883 at supratherapeutic exposure.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-07817883 Dose 1 in PART-1<br> | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 Dose 2 in PART-1<br> | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 Dose 3 in PART-1<br> | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 Dose 4 in PART-1<br> | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 Dose 5 in PART-1<br>Optional dose levels | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 Dose 6 in PART-1<br>Optional dose levels | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Placebo Comparator: Placebo in PART-1<br>A single dose of placebo | Drug: Placebo<br>* Placebo suspension<br>|
| Experimental: PF-07817883 DR1 in PART-2<br>DR=Dosing regimen; twice a day | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 DR2 in PART-2<br> | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 DR3 in PART-2<br>Optional dosing regimen | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 DR4 in PART-2<br>Optional dosing regimen | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 in Japanese in PART-2<br>Optional dosing regimen to be studied in Japanese population | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 in Chinese in PART-2<br>Optional dosing regimen to be studied in Chinese population | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Placebo Comparator: Placebo in PART-2<br> | Drug: Placebo<br>* Placebo suspension<br>|
| Experimental: PF-07817883 Suspension Fasted in PART-3<br>PART-3 is optional | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 FORM-1 Fasted in PART-3<br>First solid oral formulation (FORM1) | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 FORM-2 Fasted in PART-3<br>Second solid oral formulations (FORM-2) is optional | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 FORM-1 Fed in PART-3<br> | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 FORM-2 Fed in PART-3<br> | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: PF-07817883 in PART-4<br>PART-4 is optional | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Experimental: Midazolam 5 mg in PART-5<br>Single dose of 5 mg alone | Drug: Midazolam<br>* midazolam oral solution<br>|
| Experimental: Midazolam 5 mg with PF-07817883 in PART-5<br>Single dose of 5 mg on Day 10 with multiple doses (twice a day) of PF-07817883 | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>Drug: Midazolam<br>* midazolam oral solution<br>|
| Experimental: PF-07817883 in PART-6<br>A single dose at supratherapeutic exposure administered as divided doses (1h apart) | Drug: PF-07817883<br>* Oral suspension or solid oral formulation(s)<br>|
| Placebo Comparator: Placebo in PART-6<br>A single dose of placebo administered as divided doses (1h apart) | Drug: Placebo<br>* Placebo suspension<br>|
| Active Comparator: Moxifloxacin 400 mg in PART-6 (open label)<br>Moxifloxacin 400 mg at 0h followed by placebo at 1h | Drug: Placebo<br>* Placebo suspension<br>Drug: Moxifloxacin<br>* Moxifloxacin 400 mg tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Treatment Emergent Adverse Events (TEAEs) in PART-1:single ascending dose (SAD) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment | Day 1 to Day 5 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1:SAD | Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate. | Day 1 to Day 5 | 
| Number of Participants With Laboratory Abnormalities in PART-1:SAD | Laboratory examination includes hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose);urinalysis (decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin]). | Day 1 to Day 5 | 
| Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in PART-1:SAD | Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG | Day 1 to Day 5 | 
| Number of participants with Treatment Emergent Adverse Events (TEAEs) in PART-2:multiple ascending dose (MAD) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment | Day 1 to Day 12 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2:MAD | Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate. | Day 1 to Day 12 | 
| Number of Participants With Laboratory Abnormalities in PART-2:MAD | Laboratory examination includes hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose);urinalysis (decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin]). | Day 1 to Day 12 | 
| Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in PART-2:MAD | Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG | Day 1 to Day 12 | 
| The ratio of AUClast in PART-3:relative bioavailability (RBA)/food effect (FE) | The ratio of AUClast of test vs reference formulation | Day 1 to Day 3 | 
| The ratio of Cmax in PART-3:relative bioavailability (RBA)/food effect (FE) | The ratio of Cmax of test vs reference formulation | Day 1 to Day 3 | 
| Total % cumulative recovery of drug related material in urine and feces combined in PART-4: Metabolism and Excretion (ME) | Drug related material excreted in urine and feces combined | Day 1 to Day 11 | 
| Total % cumulative recovery of drug related material in urine combined in PART-4: Metabolism and Excretion (ME) | Drug related material excreted in urine | Day 1 to Day 11 | 
| Total % cumulative recovery of drug related material in feces combined in PART-4: Metabolism and Excretion (ME) | Drug related material excreted in feces | Day 1 to Day 11 | 
| Ratio of midazolam AUCinf or AUClast of test versus reference in PART-5:drug-drug interaction (DDI) | Ratio of midazolam AUCinf (if data permit) or AUClast of test (midazolam with PF-07817883) versus reference (midazolam alone) | Day 1 to Day 12 | 
| Number of participants with Treatment Emergent Adverse Events (TEAEs) in PART-6: Supratherapeutic Exposure (SE) | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment | Day 1 to Day 6 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-6:SE | Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate. | Day 1 to Day 6 | 
| Number of Participants With Laboratory Abnormalities in PART-6:SE | Laboratory examination includes hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose);urinalysis (decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin]). | Day 1 to Day 6 | 
| Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in PART-6:SE | Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG | Day 1 to Day 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) in PART-1:SAD | The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations | Day 1 to Day 5 | 
| Time for Cmax (Tmax) in PART-1:SAD | Observed directly from data as time of first occurrence. | Day 1 to Day 5 | 
| Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in PART-1:SAD | AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method. | Day 1 to Day 5 | 
| Dose Normalized Cmax (Cmax[dn]) in PART-1:SAD | Cmax(dn) = Cmax / dose. | Day 1 to Day 5 | 
| Dose Normalized AUClast (AUClast[dn]) in PART-1:SAD | AUClast /dose | Day 1 to Day 5 | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) in PART-1:SAD | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). | Day 1 to Day 5 | 
| Dose normalized AUCinf (AUCinf[dn]) in PART-1:SAD | AUCinf/dose | Day 1 to Day 5 | 
| Plasma Decay Half-life (t1/2) in PART-1:SAD | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 1 to Day 5 | 
| Apparent Volume of Distribution (Vz/F) in PART-1:SAD | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Day 1 to Day 5 | 
| Apparent Oral Clearance (CL/F) in PART-1:SAD | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Day 1 to Day 5 | 
| Cmax on Day 1 in PART-2:MAD |  | Day 1 Pre-dose (0 hours) to 12 hours | 
| Tmax on Day 1 in PART-2:MAD |  | Day 1 Pre-dose (0 hours) to 12 hours | 
| Area Under the Curve from Time Zero to end of dosing interval (AUCtau) on Day 1 in PART-2:MAD | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. | Day 1 Pre-dose (0 hours) to 12 hours | 
| Cmax[dn] on Day 1 in PART-2:MAD | Cmax(dn) = Cmax / dose. | Day 1 Pre-dose (0 hours) to 12 hours | 
| AUCtau[dn] on Day 1 in PART-2:MAD | AUCtau/dose | Day 1 Pre-dose (0 hours) to 12 hours | 
| Average concentration (Cav) on Day 1 in PART-2:MAD | AUCtau/12 | Day 1 Pre-dose (0 hours) to 12 hours | 
| Concentration at 12h post-dose (C12) on Day 5 in PART-2:MAD | Directly observed from the data. | Day 5 Pre-dose (0 hours) to 12 hours | 
| Cmax on Day 5 in PART-2:MAD |  | Day 5 Pre-dose (0 hours) to 12 hours | 
| Tmax on Day 5 in PART-2:MAD |  | Day 5 Pre-dose (0 hours) to 12 hours | 
| AUCtau on Day 5 in PART-2:MAD | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. | Day 5 Pre-dose (0 hours) to 12 hours | 
| Cmax[dn] on Day 5 in PART-2:MAD | Cmax(dn) = Cmax / dose. | Day 5 Pre-dose (0 hours) to 12 hours | 
| AUCtau[dn] on Day 5 in PART-2:MAD | AUCtau/dose | Day 5 Pre-dose (0 hours) to 12 hours | 
| Average concentration (Cav) on Day 5 in PART-2:MAD | AUCtau/12 | Day 5 Pre-dose (0 hours) to 12 hours | 
| Peak Trough Ratio (PTR) Day 5 in PART-2:MAD | PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It is summarized by dosing regimen . | Day 5 Pre-dose (0 hours) to 12 hours | 
| Observed Accumulation Ratio Based on AUC (Rac) on Day 5 in PART-2:MAD | Rac = AUCtau,ss / AUCtau,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac = AUCtau(Day 5) / AUCtau(Day 1). Rac is summarized by dosing regimen. | Observed Accumulation Ratio Based on AUC (Rac) in MAD-Day 5 | 
| Observed Accumulation Ratio Based on Cmax (Rac,Cmax) on Day 5 in PART-2:MAD | Rac,Cmax = Cmax,ss / Cmax,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac,Cmax = Cmax(Day5) / Cmax(Day 1). Rac,Cmax is summarized by dosing regimen. | Day 5 Pre-dose (0 hours) to 12 hours | 
| CL/F on Day 5 in PART-2:MAD | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Day 5 Pre-dose (0 hours) to 12 hours | 
| Cmax on Day 10 in PART-2:MAD |  | Day 10 Pre-dose (0 hours) to 12 hours | 
| C12 on Day 10 in PART-2:MAD | Directly observed from the data. | Day 10 Pre-dose (0 hours) to 12 hours | 
| Tmax on Day 10 in PART-2:MAD |  | Day 10 Pre-dose (0 hours) to 12 hours | 
| AUCtau on Day 10 in PART-2:MAD | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. | Day 10 Pre-dose (0 hours) to 12 hours | 
| Cmax[dn] on Day 10 in PART-2:MAD | Cmax(dn) = Cmax / dose. | Day 10 Pre-dose (0 hours) to 12 hours | 
| AUCtau[dn] on Day 10 in PART-2:MAD | AUCtau/dose | Day 10 Pre-dose (0 hours) to 12 hours | 
| Cav on Day 10 in PART-2:MAD | AUCtau/12 | Day 10 Pre-dose (0 hours) to 12 hours | 
| PTR Day 10 in PART-2:MAD | PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It is summarized by dosing regimen . | Day 10 Pre-dose (0 hours) to 12 hours | 
| Rac on Day 10 in PART-2:MAD | Rac = AUCtau,ss / AUCtau,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac = AUCtau(Day 5) / AUCtau(Day 1). Rac is summarized by dosing regimen. | Observed Accumulation Ratio Based on AUC (Rac) in MAD-Day 5 | 
| Rac,Cmax on Day 10 in PART-2:MAD | Rac,Cmax = Cmax,ss / Cmax,sd, where ss means 'at steady state' and sd 'single dose'. In this study, Rac,Cmax = Cmax(Day5) / Cmax(Day 1). Rac,Cmax is summarized by dosing regimen. | Day 10 Pre-dose (0 hours) to 12 hours | 
| CL/F on Day 10 in PART-2:MAD | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Day 10 Pre-dose (0 hours) to 12 hours | 
| t1/2 on Day 10 in PART-2:MAD | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 10 to Day 12 | 
| Vz/F on Day 10 in PART-2:MAD |  | Day 10 to Day 12 | 
| Cumulative Amount of Drug Recovered Unchanged in Urine From Time 0 to the Dosing Interval tau Hours Post-Dose (Aetau) on Day 10 in PART-2:MAD | Sum of (urine volume × urine concentration) for each collection over the dosing interval tau. Dosing interval (tau) is 12 h for BID dosing. | Day 10 Pre-dose (0 hours) to 12 hours | 
| Percentage of Dose Recovered Unchanged in Urine From Time 0 to the Dosing Interval tau Hours Post-Dose (Aetau%) on Day 10 in PART-2:MAD | Aetau% = Aetau / Dose * 100. Aetau% is summarized by dosing regimen. Dosing interval (tau) 12 h for BID dosing. | Day 10 Pre-dose (0 hours) to 12 hours | 
| Renal Clearance (Clr) on Day 10 in MAD | Renal clearance is calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Aetau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCtau), where dosing interval is 12 hours for BID dosing. | Day 10 Pre-dose (0 hours) to 12 hours | 
| The ratio of AUClast in PART-3:RBA/FE | The ratio of AUClast of test (fed) vs reference (fasted) | Day 1 to Day 3 | 
| The ratio of Cmax in PART-3:RBA/FE | The ratio of Cmax of test (fed) vs reference (fasted) | Day 1 to Day 3 | 
| The ratio of AUCinf in PART-3:RBA/FE | The ratio of AUCinf of test (fed) vs reference (fasted) | Day 1 to Day 3 | 
| Cmax in PART-3:RBA/FE |  | Day 1 to Day 3 | 
| Tmax in PART-3:RBA/FE | Observed directly from data as time of first occurrence. | Day 1 to Day 3 | 
| AUClast in PART-3:RBA/FE | AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method. | Day 1 to Day 3 | 
| AUCinf in PART-3:RBA/FE | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). | Day 1 to Day 3 | 
| t1/2 in PART-3:RBA/FE | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 1 to Day 3 | 
| Vz/F in PART-3:RBA/FE | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Day 1 to Day 3 | 
| CL/F in PART-3:RBA/FE | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Day 1 to Day 3 | 
| Cmax in PART-4:ME |  | Day 1 to Day 4 | 
| Tmax in PART-4:ME | Observed directly from data as time of first occurrence. | Day 1 to Day 4 | 
| AUClast in PART-4:ME | AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method. | Day 1 to Day 4 | 
| AUCinf in PART-4:ME | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). | Day 1 to Day 4 | 
| t1/2 in PART-4:ME | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 1 to Day 4 | 
| Vz/F in PART-4:ME | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Day 1 to Day 4 | 
| CL/F in PART-4:ME | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. | Day 1 to Day 4 | 
| Cmax of midazolam, when administered alone, in PART-5:DDI |  | Day 1 to Day 3 | 
| Cmax of midazolam, when administered with PF-07817883, in PART-5:DDI |  | Day 1 to Day 3 | 
| Tmax of midazolam, when administered alone, in PART-5:DDI |  | Day 1 to Day 3 | 
| Tmax of midazolam, when administered with PF-07817883, in PART-5:DDI |  | Day 1 to Day 3 | 
| AUClast of midazolam, when administered alone, in PART-5:DDI |  | Day 1 to Day 3 | 
| AUClast of midazolam, when administered with PF-07817883, in PART-5:DDI |  | Day 1 to Day 3 | 
| AUCinf of midazolam, when administered alone, in PART-5:DDI |  | Day 1 to Day 3 | 
| AUCinf of midazolam, when administered with PF-07817883, in PART-5:DDI |  | Day 1 to Day 3 | 
| CL/F of midazolam, when administered alone, in PART-5:DDI |  | Day 1 to Day 3 | 
| CL/F of midazolam, when administered with PF-07817883, in PART-5:DDI |  | Day 1 to Day 3 | 
| Vz/F of midazolam, when administered alone, in PART-5:DDI |  | Day 1 to Day 3 | 
| Vz/F of midazolam, when administered with PF-07817883, in PART-5:DDI |  | Day 1 to Day 3 | 
| Number of participants with TEAEs in PART-3:RBA/FE | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment | Day 1 to Day 3 | 
| Number of participants with TEAEs in PART-4:ME | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment | Day 1 to Day 11 | 
| Number of participants with TEAEs in PART-5:DDI | An Adverse Event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) is defined as any untoward medical occurrence at any dose that results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; results in congenital anomaly/birth defect. AEs include both SAEs and AEs. TEAEs are AEs that occur following the start of treatment or AEs increasing in severity during treatment | Day 1 to Day 12 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-3:RBA/FE | Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate. | Day 1 to Day 3 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-4:ME | Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate. | Day 1 to Day 11 | 
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5:DDI | Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate. | Day 1 to Day 12 | 
| Number of Participants With Laboratory Abnormalities in PART-3:RBA/FE | Laboratory examination includes hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose);urinalysis (decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin]). | Day 1 to Day 3 | 
| Number of Participants With Laboratory Abnormalities in PART-4:ME | Laboratory examination includes hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose);urinalysis (decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin]). | Day 1 to Day 11 | 
| Number of Participants With Laboratory Abnormalities in PART-5:DDI | Laboratory examination includes hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, bicarbonate); clinical chemistry (glucose);urinalysis (decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin]). | Day 1 to Day 12 | 
| Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in PART-3:RBA/FE | Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG | Day 1 to Day 3 | 
| Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in PART-4:ME | Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG | Day 1 to Day 11 | 
| Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in PART-5:DDI | Criteria for clinically significant changes in ECG (12-lead) are defined as: a postdose QTc interval increase by ≥30 msec from the baseline and is >450 msec; or an absolute QTc value is ≥500 msec for any scheduled ECG | Day 1 to Day 12 | 
| Cmax in PART-6:SE | The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations | Day 1 to Day 6 | 
| Tmax in PART-6:SE | Observed directly from data as time of first occurrence. | Day 1 to Day 6 | 
| AUClast in PART-6:SE | AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method. | Day 1 to Day 6 | 
| AUCinf in PART-6:SE | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). | Day 1 to Day 6 | 
| t1/2 in PART-6:SE | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. | Day 1 to Day 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Oral Antiviral, COVID-19, Protease Inhibitor, Mpro, PF-07817883