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

Healthy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05580003
• Other study ID #: C5091001
• Secondary ID: 2022-002871-1220
• Status: Completed
• Phase: Phase 1
• Start date: October 17, 2022
• Est. completion date: September 15, 2023

Study information

• Verified date: September 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: September 15, 2023
• Est. primary completion date: September 15, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy

Intervention

Drug:
• PF-07817883
Oral suspension or solid oral formulation(s)
• Placebo
Placebo suspension
• Midazolam
midazolam oral solution
• Moxifloxacin
Moxifloxacin 400 mg tablet

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit - Brussels	Brussels	Bruxelles-capitale, Région DE
United States	New Haven Clinical Research Unit	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	Time for Cmax (Tmax) in PART-1:SAD	Observed directly from data as time of first occurrence.	Day 1 to Day 5
Secondary	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
Secondary	Dose Normalized Cmax (Cmax[dn]) in PART-1:SAD	Cmax(dn) = Cmax / dose.	Day 1 to Day 5
Secondary	Dose Normalized AUClast (AUClast[dn]) in PART-1:SAD	AUClast /dose	Day 1 to Day 5
Secondary	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
Secondary	Dose normalized AUCinf (AUCinf[dn]) in PART-1:SAD	AUCinf/dose	Day 1 to Day 5
Secondary	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
Secondary	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
Secondary	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
Secondary	Cmax on Day 1 in PART-2:MAD		Day 1 Pre-dose (0 hours) to 12 hours
Secondary	Tmax on Day 1 in PART-2:MAD		Day 1 Pre-dose (0 hours) to 12 hours
Secondary	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
Secondary	Cmax[dn] on Day 1 in PART-2:MAD	Cmax(dn) = Cmax / dose.	Day 1 Pre-dose (0 hours) to 12 hours
Secondary	AUCtau[dn] on Day 1 in PART-2:MAD	AUCtau/dose	Day 1 Pre-dose (0 hours) to 12 hours
Secondary	Average concentration (Cav) on Day 1 in PART-2:MAD	AUCtau/12	Day 1 Pre-dose (0 hours) to 12 hours
Secondary	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
Secondary	Cmax on Day 5 in PART-2:MAD		Day 5 Pre-dose (0 hours) to 12 hours
Secondary	Tmax on Day 5 in PART-2:MAD		Day 5 Pre-dose (0 hours) to 12 hours
Secondary	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
Secondary	Cmax[dn] on Day 5 in PART-2:MAD	Cmax(dn) = Cmax / dose.	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	AUCtau[dn] on Day 5 in PART-2:MAD	AUCtau/dose	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	Average concentration (Cav) on Day 5 in PART-2:MAD	AUCtau/12	Day 5 Pre-dose (0 hours) to 12 hours
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cmax on Day 10 in PART-2:MAD		Day 10 Pre-dose (0 hours) to 12 hours
Secondary	C12 on Day 10 in PART-2:MAD	Directly observed from the data.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Tmax on Day 10 in PART-2:MAD		Day 10 Pre-dose (0 hours) to 12 hours
Secondary	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
Secondary	Cmax[dn] on Day 10 in PART-2:MAD	Cmax(dn) = Cmax / dose.	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	AUCtau[dn] on Day 10 in PART-2:MAD	AUCtau/dose	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	Cav on Day 10 in PART-2:MAD	AUCtau/12	Day 10 Pre-dose (0 hours) to 12 hours
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Vz/F on Day 10 in PART-2:MAD		Day 10 to Day 12
Secondary	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
Secondary	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
Secondary	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
Secondary	The ratio of AUClast in PART-3:RBA/FE	The ratio of AUClast of test (fed) vs reference (fasted)	Day 1 to Day 3
Secondary	The ratio of Cmax in PART-3:RBA/FE	The ratio of Cmax of test (fed) vs reference (fasted)	Day 1 to Day 3
Secondary	The ratio of AUCinf in PART-3:RBA/FE	The ratio of AUCinf of test (fed) vs reference (fasted)	Day 1 to Day 3
Secondary	Cmax in PART-3:RBA/FE		Day 1 to Day 3
Secondary	Tmax in PART-3:RBA/FE	Observed directly from data as time of first occurrence.	Day 1 to Day 3
Secondary	AUClast in PART-3:RBA/FE	AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.	Day 1 to Day 3
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cmax in PART-4:ME		Day 1 to Day 4
Secondary	Tmax in PART-4:ME	Observed directly from data as time of first occurrence.	Day 1 to Day 4
Secondary	AUClast in PART-4:ME	AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.	Day 1 to Day 4
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cmax of midazolam, when administered alone, in PART-5:DDI		Day 1 to Day 3
Secondary	Cmax of midazolam, when administered with PF-07817883, in PART-5:DDI		Day 1 to Day 3
Secondary	Tmax of midazolam, when administered alone, in PART-5:DDI		Day 1 to Day 3
Secondary	Tmax of midazolam, when administered with PF-07817883, in PART-5:DDI		Day 1 to Day 3
Secondary	AUClast of midazolam, when administered alone, in PART-5:DDI		Day 1 to Day 3
Secondary	AUClast of midazolam, when administered with PF-07817883, in PART-5:DDI		Day 1 to Day 3
Secondary	AUCinf of midazolam, when administered alone, in PART-5:DDI		Day 1 to Day 3
Secondary	AUCinf of midazolam, when administered with PF-07817883, in PART-5:DDI		Day 1 to Day 3
Secondary	CL/F of midazolam, when administered alone, in PART-5:DDI		Day 1 to Day 3
Secondary	CL/F of midazolam, when administered with PF-07817883, in PART-5:DDI		Day 1 to Day 3
Secondary	Vz/F of midazolam, when administered alone, in PART-5:DDI		Day 1 to Day 3
Secondary	Vz/F of midazolam, when administered with PF-07817883, in PART-5:DDI		Day 1 to Day 3
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cmax in PART-6:SE	The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations	Day 1 to Day 6
Secondary	Tmax in PART-6:SE	Observed directly from data as time of first occurrence.	Day 1 to Day 6
Secondary	AUClast in PART-6:SE	AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.	Day 1 to Day 6
Secondary	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
Secondary	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

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