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

Sponsor

Pfizer (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05580003

Collaborator

(none)

Enrollment

Locations

Arms

5.2

Anticipated Duration (Months)

Patients Per Site

8.7

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: PF-07817883 Drug: Placebo Drug: Midazolam	Phase 1

Detailed Description

Combined 5-part study. Part-1: Single Ascending dose Part-2: Multiple Ascending Dose Part-3:

Optional Relative bioavailability and food effect Part-4: Optional Metabolism and Excretion Part-5: Optional drug-drug interaction with midazolam Part-1 and 2 are double blind, sponsor open and Part-3,4 and 5 are open label study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention 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. Optional 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. Optional PART-4 is an open label, non-randomized, single period cohort to evaluate the metabolism and excretion of PF 07817883. Optional 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-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. Optional 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. Optional PART-4 is an open label, non-randomized, single period cohort to evaluate the metabolism and excretion of PF 07817883. Optional 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.

Masking:

Double (Participant, Investigator)

Masking Description:

PART-1 and -2 are double-blind, sponsor-open while PART-3, 4 and 5 are open label

Primary Purpose:

Other

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

Actual Study Start Date :

Oct 17, 2022

Anticipated Primary Completion Date :

Mar 23, 2023

Anticipated Study Completion Date :

Mar 23, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-07817883 Dose 1 in PART-1	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 Dose 2 in PART-1	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 Dose 3 in PART-1	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 Dose 4 in PART-1	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 Dose 5 in PART-1 Optional dose levels	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 Dose 6 in PART-1 Optional dose levels	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Placebo Comparator: Placebo in PART-1 A single dose of placebo	Drug: Placebo Placebo suspension
Experimental: PF-07817883 DR1 in PART-2 DR=Dosing regimen; twice a day	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 DR2 in PART-2	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 DR3 in PART-2 Optional dosing regimen	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 DR4 in PART-2 Optional dosing regimen	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 in Japanese in PART-2 Optional dosing regimen to be studied in Japanese population	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 in Chinese in PART-2 Optional dosing regimen to be studied in Chinese population	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Placebo Comparator: Placebo in PART-2	Drug: Placebo Placebo suspension
Experimental: PF-07817883 Suspension Fasted in PART-3 PART-3 is optional	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 FORM-1 Fasted in PART-3 First solid oral formulation (FORM1)	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 FORM-2 Fasted in PART-3 Second solid oral formulations (FORM-2) is optional	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 FORM-1 Fed in PART-3	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 FORM-2 Fed in PART-3	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: PF-07817883 in PART-4 PART-4 is optional	Drug: PF-07817883 Oral suspension or solid oral formulation(s)
Experimental: Midazolam 5 mg in PART-5 Single dose of 5 mg alone	Drug: Midazolam midazolam oral solution
Experimental: 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	Drug: PF-07817883 Oral suspension or solid oral formulation(s) Drug: Midazolam midazolam oral solution

Outcome Measures

Primary Outcome Measures

Number of participants with Treatment Emergent Adverse Events (TEAEs) in PART-1:single ascending dose (SAD) [Day 1 to Day 5]
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
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1:SAD [Day 1 to Day 5]
Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate.
Number of Participants With Laboratory Abnormalities in PART-1:SAD [Day 1 to Day 5]
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]).
Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in PART-1:SAD [Day 1 to Day 5]
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
Number of participants with Treatment Emergent Adverse Events (TEAEs) in PART-2:multiple ascending dose (MAD) [Day 1 to Day 12]
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
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2:MAD [Day 1 to Day 12]
Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate.
Number of Participants With Laboratory Abnormalities in PART-2:MAD [Day 1 to Day 12]
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]).
Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in PART-2:MAD [Day 1 to Day 12]
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
The ratio of AUClast in Optional PART-3:relative bioavailability (RBA)/food effect (FE) [Day 1 to Day 3]
The ratio of AUClast of test vs reference formulation
The ratio of Cmax in Optional PART-3:relative bioavailability (RBA)/food effect (FE) [Day 1 to Day 3]
The ratio of Cmax of test vs reference formulation
Total % cumulative recovery of drug related material in urine and feces combined in Optional PART-4: Metabolism and Excretion (ME) [Day 1 to Day 11]
Drug related material excreted in urine and feces combined
Total % cumulative recovery of drug related material in urine combined in Optional PART-4: Metabolism and Excretion (ME) [Day 1 to Day 11]
Drug related material excreted in urine
Total % cumulative recovery of drug related material in feces combined in Optional PART-4: Metabolism and Excretion (ME) [Day 1 to Day 11]
Drug related material excreted in feces
Ratio of midazolam AUCinf or AUClast of test versus reference in Optional PART-5:drug-drug interaction (DDI) [Day 1 to Day 12]
Ratio of midazolam AUCinf (if data permit) or AUClast of test (midazolam with PF-07817883) versus reference (midazolam alone)

Secondary Outcome Measures

Maximum Plasma Concentration (Cmax) in PART-1:SAD [Day 1 to Day 5]
The maximum observed plasma concentration (Cmax) is estimated based on the plasma concentrations
Time for Cmax (Tmax) in PART-1:SAD [Day 1 to Day 5]
Observed directly from data as time of first occurrence.
Area Under the Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) in PART-1:SAD [Day 1 to Day 5]
AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.
Dose Normalized Cmax (Cmax[dn]) in PART-1:SAD [Day 1 to Day 5]
Cmax(dn) = Cmax / dose.
Dose Normalized AUClast (AUClast[dn]) in PART-1:SAD [Day 1 to Day 5]
AUClast /dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) in PART-1:SAD [Day 1 to Day 5]
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).
Dose normalized AUCinf (AUCinf[dn]) in PART-1:SAD [Day 1 to Day 5]
AUCinf/dose
Plasma Decay Half-life (t1/2) in PART-1:SAD [Day 1 to Day 5]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Apparent Volume of Distribution (Vz/F) in PART-1:SAD [Day 1 to Day 5]
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.
Apparent Oral Clearance (CL/F) in PART-1:SAD [Day 1 to Day 5]
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.
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 [Day 1 Pre-dose (0 hours) to 12 hours]
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Cmax[dn] on Day 1 in PART-2:MAD [Day 1 Pre-dose (0 hours) to 12 hours]
Cmax(dn) = Cmax / dose.
AUCtau[dn] on Day 1 in PART-2:MAD [Day 1 Pre-dose (0 hours) to 12 hours]
AUCtau/dose
Average concentration (Cav) on Day 1 in PART-2:MAD [Day 1 Pre-dose (0 hours) to 12 hours]
AUCtau/12
Concentration at 12h post-dose (C12) on Day 5 in PART-2:MAD [Day 5 Pre-dose (0 hours) to 12 hours]
Directly observed from the data.
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 [Day 5 Pre-dose (0 hours) to 12 hours]
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Cmax[dn] on Day 5 in PART-2:MAD [Day 5 Pre-dose (0 hours) to 12 hours]
Cmax(dn) = Cmax / dose.
AUCtau[dn] on Day 5 in PART-2:MAD [Day 5 Pre-dose (0 hours) to 12 hours]
AUCtau/dose
Average concentration (Cav) on Day 5 in PART-2:MAD [Day 5 Pre-dose (0 hours) to 12 hours]
AUCtau/12
Peak Trough Ratio (PTR) Day 5 in PART-2:MAD [Day 5 Pre-dose (0 hours) to 12 hours]
PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It is summarized by dosing regimen .
Observed Accumulation Ratio Based on AUC (Rac) on Day 5 in PART-2:MAD [Observed Accumulation Ratio Based on AUC (Rac) in MAD-Day 5]
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 Cmax (Rac,Cmax) on Day 5 in PART-2:MAD [Day 5 Pre-dose (0 hours) to 12 hours]
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.
CL/F on Day 5 in PART-2:MAD [Day 5 Pre-dose (0 hours) to 12 hours]
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.
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 [Day 10 Pre-dose (0 hours) to 12 hours]
Directly observed from the data.
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 [Day 10 Pre-dose (0 hours) to 12 hours]
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Cmax[dn] on Day 10 in PART-2:MAD [Day 10 Pre-dose (0 hours) to 12 hours]
Cmax(dn) = Cmax / dose.
AUCtau[dn] on Day 10 in PART-2:MAD [Day 10 Pre-dose (0 hours) to 12 hours]
AUCtau/dose
Cav on Day 10 in PART-2:MAD [Day 10 Pre-dose (0 hours) to 12 hours]
AUCtau/12
PTR Day 10 in PART-2:MAD [Day 10 Pre-dose (0 hours) to 12 hours]
PTR = Cmax,ss / Cmin,ss, where ss means 'at steady state'. It is summarized by dosing regimen .
Rac on Day 10 in PART-2:MAD [Observed Accumulation Ratio Based on AUC (Rac) in MAD-Day 5]
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.
Rac,Cmax on Day 10 in PART-2:MAD [Day 10 Pre-dose (0 hours) to 12 hours]
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.
CL/F on Day 10 in PART-2:MAD [Day 10 Pre-dose (0 hours) to 12 hours]
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.
t1/2 on Day 10 in PART-2:MAD [Day 10 to Day 12]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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 [Day 10 Pre-dose (0 hours) to 12 hours]
Sum of (urine volume × urine concentration) for each collection over the dosing interval tau. Dosing interval (tau) is 12 h for BID dosing.
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 [Day 10 Pre-dose (0 hours) to 12 hours]
Aetau% = Aetau / Dose * 100. Aetau% is summarized by dosing regimen. Dosing interval (tau) 12 h for BID dosing.
Renal Clearance (Clr) on Day 10 in MAD [Day 10 Pre-dose (0 hours) to 12 hours]
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.
The ratio of AUClast in Optional PART-3:RBA/FE [Day 1 to Day 3]
The ratio of AUClast of test (fed) vs reference (fasted)
The ratio of Cmax in Optional PART-3:RBA/FE [Day 1 to Day 3]
The ratio of Cmax of test (fed) vs reference (fasted)
The ratio of AUCinf in Optional PART-3:RBA/FE [Day 1 to Day 3]
The ratio of AUCinf of test (fed) vs reference (fasted)
Cmax in Optional PART-3:RBA/FE [Day 1 to Day 3]
Tmax in Optional PART-3:RBA/FE [Day 1 to Day 3]
Observed directly from data as time of first occurrence.
AUClast in Optional PART-3:RBA/FE [Day 1 to Day 3]
AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.
AUCinf in Optional PART-3:RBA/FE [Day 1 to Day 3]
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).
t1/2 in Optional PART-3:RBA/FE [Day 1 to Day 3]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Vz/F in Optional PART-3:RBA/FE [Day 1 to Day 3]
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.
CL/F in Optional PART-3:RBA/FE [Day 1 to Day 3]
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.
Cmax in Optional PART-4:ME [Day 1 to Day 4]
Tmax in Optional PART-4:ME [Day 1 to Day 4]
Observed directly from data as time of first occurrence.
AUClast in Optional PART-4:ME [Day 1 to Day 4]
AUClast is summarized by dosing regimen and determined by linear/log trapezoidal method.
AUCinf in Optional PART-4:ME [Day 1 to Day 4]
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).
t1/2 in Optional PART-4:ME [Day 1 to Day 4]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Vz/F in Optional PART-4:ME [Day 1 to Day 4]
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.
CL/F in Optional PART-4:ME [Day 1 to Day 4]
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.
Cmax of midazolam, when administered alone, in Optional PART-5:DDI [Day 1 to Day 3]
Cmax of midazolam, when administered with PF-07817883, in Optional PART-5:DDI [Day 1 to Day 3]
Tmax of midazolam, when administered alone, in Optional PART-5:DDI [Day 1 to Day 3]
Tmax of midazolam, when administered with PF-07817883, in Optional PART-5:DDI [Day 1 to Day 3]
AUClast of midazolam, when administered alone, in Optional PART-5:DDI [Day 1 to Day 3]
AUClast of midazolam, when administered with PF-07817883, in Optional PART-5:DDI [Day 1 to Day 3]
AUCinf of midazolam, when administered alone, in Optional PART-5:DDI [Day 1 to Day 3]
AUCinf of midazolam, when administered with PF-07817883, in Optional PART-5:DDI [Day 1 to Day 3]
CL/F of midazolam, when administered alone, in Optional PART-5:DDI [Day 1 to Day 3]
CL/F of midazolam, when administered with PF-07817883, in Optional PART-5:DDI [Day 1 to Day 3]
Vz/F of midazolam, when administered alone, in Optional PART-5:DDI [Day 1 to Day 3]
Vz/F of midazolam, when administered with PF-07817883, in Optional PART-5:DDI [Day 1 to Day 3]
Number of participants with TEAEs in Optional PART-3:RBA/FE [Day 1 to Day 3]
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
Number of participants with TEAEs in Optional PART-4:ME [Day 1 to Day 11]
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
Number of participants with TEAEs in Optional PART-5:DDI [Day 1 to Day 12]
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
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in Optional PART-3:RBA/FE [Day 1 to Day 3]
Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in Optional PART-4:ME [Day 1 to Day 11]
Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in Optional PART-5:DDI [Day 1 to Day 12]
Vital signs evaluation includes: supine systolic and diastolic blood pressure (BP), respiratory rate and pulse rate.
Number of Participants With Laboratory Abnormalities in Optional PART-3:RBA/FE [Day 1 to Day 3]
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]).
Number of Participants With Laboratory Abnormalities in Optional PART-4:ME [Day 1 to Day 11]
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]).
Number of Participants With Laboratory Abnormalities in Optional PART-5:DDI [Day 1 to Day 12]
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]).
Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in Optional PART-3:RBA/FE [Day 1 to Day 3]
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
Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in Optional PART-4:ME [Day 1 to Day 11]
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
Number of Participants with Clinically Significant Change From Baseline in Electrocardiogram (ECG) Findings in Optional PART-5:DDI [Day 1 to Day 12]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	New Haven Clinical Research Unit	New Haven	Connecticut	United States	06511
2	Brussels Clinical Research Unit	Brussels	Bruxelles-capitale, Région DE	Belgium	B-1070