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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: PF-07817883; Drug: Placebo; Drug: Midazolam; Drug: Moxifloxacin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 94
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Pfizer Clinical Research Unit - Brussels
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

25

Arms and Interventions

Participant Group / 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
Experimental: PF-07817883 in PART-6; A single dose at supratherapeutic exposure administered as divided doses (1h apart)	Drug: PF-07817883; Oral suspension or solid oral formulation(s)
Placebo Comparator: Placebo in PART-6; A single dose of placebo administered as divided doses (1h apart)	Drug: Placebo; Placebo suspension
Active Comparator: Moxifloxacin 400 mg in PART-6 (open label); Moxifloxacin 400 mg at 0h followed by placebo at 1h	Drug: Placebo; Placebo suspension; Drug: Moxifloxacin; Moxifloxacin 400 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.	From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 days)
Part 1: Number of Participants With Laboratory Test Abnormalities	Laboratory parameters included: (lymphocytes less than (<) 0.8*lower limit of normal [LLN] [10^3 per millimeter cube {mm3}], lymphocytes/leukocytes <0.8*LLN [percentage {%}], neutrophils <0.8*LLN [10^3/mm3], neutrophils/leukocytes <0.8*LLN [%], monocytes/leukocytes greater than (>) 1.2*upper limit of normal [ULN] [%], partial thromboplastin time >1.1*ULN [seconds]), chemistry (bicarbonate <0.9*LLN [milliequivalents per liter {mEq/L}], creatine kinase >2.0*ULN [units per liter {U/L}], lipase >1.5*ULN [U/L]), and urinalysis (urine hemoglobin greater than or equal to [>=] 1, leukocyte esterase >=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.	From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 48 days)
Part 1: Number of Participants With Vital Signs Meeting Pre-Defined Criteria	Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate (PR) were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value less than (<) 90 millimeter of mercury (mmHg), change greater than or equal to (>=) 30 mmHg increase, change >= 30 mmHg decrease; DBP: value < 50 mmHg, change >= 20 mmHg increase, change >= 20 mmHg decrease; PR: value < 40 beats per minute (bpm), value > 120 bpm.	Up to Day 2 of each period
Part 1: Number of Participants With Electrocardiogram (ECG) Abnormalities	Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.	Up to Day 2 of each period
Part 2: Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.	From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 days)
Part 2: Number of Participants With Laboratory Test Abnormalities	Laboratory parameters included: hematology (lymphocytes/leukocytes >1.2*ULN [%], neutrophils <0.8*LLN [10^3/mm3], neutrophils/leukocytes <0.8*LLN [%], monocytes/leukocytes >1.2*ULN [%]), chemistry (urate >1.2*ULN [milligrams per deciliter] {mg/dL}), and urinalysis (ketones >=1, urine hemoglobin >=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.	From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 55 days)
Part 2: Number of Participants With Vital Signs Meeting Pre-Defined Criteria	Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value < 90 mmHg, change >= 30 mmHg increase, change >= 30 mmHg decrease; DBP: value < 50 mmHg, change >= 20 mmHg increase, change >= 20 mmHg decrease; PR: value < 40 bpm, value > 120 bpm. 4. Number of participants with vital signs meeting any of the pre-defined criteria is reported in this outcome measure.	Up to Day 12
Part 2: Number of Participants With Electrocardiogram (ECG) Abnormalities	Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.	Up to Day 12
Part 3:Ratio Based on Area Under Plasma Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) and Area Under Concentration-Time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) of Oral Formulation and Suspension	Data for AUClast and AUCinf are reported in the descriptive section. AUClast was calculated by the linear/log trapezoidal method. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis. Ratio based on AUClast and AUCinf of oral formulation and suspension were reported in statistical analysis.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Oral Formulation and Suspension	Data for Cmax are reported in the descriptive section. Ratio based on Cmax of oral formulation and suspension were reported in statistical analysis.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 4: Percentage of Total Dose Administered Recovered in Urine	The percentage of total dose administered recovered in urine was reported in this outcome measure.	Up to 144 hours post-dose
Part 4: Percentage of Total Dose Administered Recovered in Feces	The percentage of total dose administered recovered in feces was reported in this outcome measure.	Up to 144 hours post-dose
Part 4: Percentage of Total Dose Administered Recovered in Urine and Feces	The percentage of total dose administered recovered in urine and feces was reported in this outcome measure.	Up to 144 hours post-dose
Part 5: Maximum Observed Concentration (Cmax) of Midazolam	Cmax of midazolam was reported in this outcome measure.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm
Part 5: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of Midazolam	AUCinf of midazolam was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm
Part 6: Number of Participants With TEAEs	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.	From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 days)
Part 6: Number of Participants With Laboratory Test Abnormalities	Laboratory parameters included: hematology (lymphocytes <0.6*LLN [10^3/mm3], lymphocytes/leukocytes >1.2*ULN [%], neutrophils <0.8*LLN [10^3/mm3], neutrophils/leukocytes <0.8*LLN [%], basophils/leukocytes >1.2*ULN [%], eosinophils/leukocytes >1.2*ULN [%], monocytes/leukocytes >1.2*ULN [%], partial thromboplastin time >1.1*ULN [seconds], prothrombin time >1.1*ULN [seconds]), chemistry (bicarbonate <0.9*LLN [mEq/L], creatine kinase > 2.0*ULN [U/L], lipase > 1.5*ULN [U/L], urobilinogen >=1 [ehrlich units/deciliter] {EU/dL}) and urinalysis (urine hemoglobin >=1, leukocyte esterase >=1, ketones >=1, bacteria >20 [per low power field] {/lpf}). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.	From start of study treatment up to 28-35 days after administration of last dose of study intervention (maximum up to 52 days)
Part 6: Number of Participants With Vital Signs Meeting Pre-Defined Criteria	Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value < 90 mmHg, change >= 30 mmHg increase, change >= 30 mmHg decrease; DBP: value < 50 mmHg, change >= 20 mmHg increase, change >= 20 mmHg decrease; PR: value < 40 bpm, value > 120 bpm.	Up to Day 6 of each period
Part 6: Number of Participants According to Categorization of ECG Data	Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured QTcF interval, aggregate 450 milliseconds (msec) < value <= 480 msec and QTcF interval, aggregate 30 msec < change <= 60 msec. Number of participants with abnormalities in ECG were reported in this outcome measure.	Up to Day 6 of each period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Maximum Observed Concentration (Cmax) of PF-07817883	Cmax of PF-07817883 was reported in this outcome measure.	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 1: Time for Cmax (Tmax) of PF-07817883	Tmax of PF-07817883 was reported in this outcome measure.	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 1: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883	AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 1: Dose Normalized Cmax (Cmax[dn]) of PF-07817883	Cmax(dn) of PF-07817883 was reported in this outcome measure. Cmax(dn) was calculated as Cmax/dose.	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 1: Dose Normalized AUClast (AUClast[dn]) of PF-07817883	AUClast(dn) of PF-07817883 was reported in this outcome measure. AUClast(dn) was calculated by AUClast/dose.	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 1: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883	AUCinf of PF-07817883 was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 1: Dose Normalized AUCinf (AUCinf[dn]) of PF-07817883	AUCinf(dn) of PF-07817883 was reported in this outcome measure. AUCinf(dn) was calculated as AUCinf/dose.	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 1: Terminal Half-Life (t1/2) of PF-07817883	t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 1: Apparent Volume of Distribution (Vz/F) of PF-07817883	Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCinf*kel).	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 1: Apparent Clearance (CL/F) of PF-07817883	CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.	Day 1 (pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 2: Maximum Observed Concentration (Cmax) of PF-07817883 on Days 1, 5 and 10	Cmax of PF-07817883 was reported in this outcome measure.	Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 2: Time for Cmax (Tmax) of PF-07817883 on Days 1, 5 and 10	Tmax of PF-07817883 was reported in this outcome measure.	Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 2: Area Under the Plasma Concentration-Time Profile From Time 0 to Time Tau, the Dosing Interval (AUCtau) of PF-07817883 on Days 1, 5 and 10	AUCtau was defined as area under the plasma concentration-time profile from time 0 to time tau, the dosing interval, where tau= 12 hours. AUCtau of PF-07817883 was reported in this outcome measure. AUCtau was calculated by linear/log trapezoidal method.	Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose)
Part 2: Concentration at 12 Hour Nominal Time Post-Dose (C12) of PF-07817883 on Days 5 and 10	C12 of PF-07817883 was reported in this outcome measure.	12 hours on Day 5 and Day 10
Part 2: Dose Normalized Cmax (Cmax[dn]) of PF-07817883 on Days 1, 5 and 10	Cmax(dn) of PF-07817883 was reported in this outcome measure. Cmax(dn) was calculated as Cmax/dose.	Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 2: Dose Normalized AUCtau (AUCtau[dn]) of PF-07817883 on Days 1, 5 and 10	AUCtau(dn) was defined as dose normalized AUCtau, where tau= 12 hours. AUCtau(dn) of PF-07817883 was reported in this outcome measure. AUCtau(dn) was calculated as AUCtau/dose.	Day 1 and Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose)
Part 2: Average Concentration (Cav) of PF-07817883 on Days 5 and 10	Cav of PF-07817883 was reported in this outcome measure. Cav was calculated as AUCtau/12.	Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose)
Part 2: Observed Accumulation Ratio for AUCtau (Rac) of PF-07817883 on Days 5 and 10	Rac was defined as observed accumulation ratio for AUCtau, where tau= 12 hours. Rac of PF-07817883 was reported in this outcome measure. Rac was calculated as AUCtau on Day 5 or Day 10/AUCtau on Day 1.	Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose)
Part 2: Observed Accumulation Ratio for Cmax (Rac,Cmax) of PF-07817883 on Days 5 and 10	Rac,Cmax of PF-07817883 was reported in this outcome measure. Rac,Cmax was calculated as Cmax on Day 5 or Day 10/Cmax on Day 1.	Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 2: Peak-to-Trough Ratio (PTR) of PF-07817883 on Days 5 and 10	PTR of PF-07817883 was reported in this outcome measure. PTR was calculated as Cmax/Cmin.	Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 2: Apparent Clearance (CL/F) of PF-07817883 on Days 5 and 10	CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.	Day 5 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose) and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 2: Apparent Volume of Distribution (Vz/F) of PF-07817883 on Day 10	Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCtau*kel).	Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 2: Terminal Half-Life (t1/2) of PF-07817883 on Day 10	t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.	Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 2: Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) of PF-07817883 on Day 10	Aetau was defined as amount excreted in urine as unchanged drug over the dosing interval tau, where tau= 12 hours. Aetau of PF-07817883 was reported in this outcome measure. Aetau was calculated as sum of (urine volume*urine concentration) for each collection over the dosing interval.	Day 10 (0 to 12 hours)
Part 2: Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) of PF-07817883 on Day 10	Aetau% was defined as percentage of dose excreted in urine as unchanged drug over the dosing interval tau, where tau= 12 hours. Aetau% of PF-07817883 was reported in this outcome measure. Aetau% was calculated as 100*Aetau/dose.	Day 10 (0 to 12 hours)
Part 2: Renal Clearance (CLr) of PF-07817883 on Day 10	CLr of PF-07817883 was reported in this outcome measure. CLr was calculated as Aetau/AUCtau.	Day 10 (0 to 12 hours)
Part 3: Ratio Based on AUClast and AUCinf of Tablet Formulation Under Fed Condition and Fasted Condition	Data for AUClast and AUCinf are reported in the descriptive section. AUClast was calculated by the linear/log trapezoidal method. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis. Ratio based on AUClast and AUCinf of tablet formulations under fed and fasted conditions were reported in statistical analysis.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Ratio Based on Maximum Observed Concentration (Cmax) of Tablet Formulation Under Fed Condition and Fasted Condition	Data for Cmax are reported in the descriptive section. Ratio based on Cmax of tablet formulation under fed and fasted conditions were reported in statistical analysis.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Time for Cmax (Tmax) of PF-07817883	Tmax of PF-07817883 was reported in this outcome measure.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Maximum Observed Concentration (Cmax) of PF-07817883	Cmax of PF-07817883 was reported in this outcome measure.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883	AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883	AUCinf of PF-07817883 was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Terminal Half-Life (t1/2) of PF-07817883	t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Apparent Clearance (CL/F) of PF-07817883	CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Apparent Volume of Distribution (Vz/F) of PF-07817883	Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCtau*kel).	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 hours post-dose)
Part 3: Number of Participants With TEAEs	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.	From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 49 days)
Part 3: Number of Participants With Laboratory Test Abnormalities	Laboratory parameters included: hematology (monocytes/leukocytes >1.2*ULN [%], partial thromboplastin time >1.1*ULN [seconds]) and urinalysis (urine hemoglobin >=1, bacteria >20 [/lpf]). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.	From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 49 days)
Part 3: Number of Participants With Vital Signs Meeting Pre-Defined Criteria	Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value < 90 mmHg, change >= 30 mmHg increase, change >= 30 mmHg decrease; DBP: value < 50 mmHg, change >= 20 mmHg increase, change >= 20 mmHg decrease; PR: value < 40 bpm, value > 120 bpm. 4. Number of participants with vital signs meeting any of the pre-defined criteria is reported in this outcome measure.	Up to Day 3 of each period
Part 3: Number of Participants With ECG Abnormalities	Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.	Up to Day 3 of each period
Part 4: Time for Cmax (Tmax) of PF-07817883	Tmax of PF-07817883 was reported in this outcome measure.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 4: Maximum Observed Concentration (Cmax) of PF-07817883	Cmax of PF-07817883 was reported in this outcome measure.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 4: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883	AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 4: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883	AUCinf of PF-07817883 was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 4: Terminal Half-Life (t1/2) of PF-07817883	t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 4: Apparent Clearance (CL/F) of PF-07817883	CL/F of PF-07817883 was reported in this outcome measure. CL/F was calculated as dose/AUCinf.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 4: Apparent Volume of Distribution (Vz/F) of PF-07817883	Vz/F of PF-07817883 was reported in this outcome measure. Vz/F was calculated as dose/(AUCtau*kel).	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48, 72 hours post-dose)
Part 4: Number of Participants With TEAEs	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.	From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 47 days)
Part 4: Number of Participants With Laboratory Test Abnormalities	Laboratory parameters included: hematology (mean corpuscular volume <0.9*LLN [cubic micrometer {um^3}], mean corpuscular hemoglobin <0.9*LLN [picograms per cell {pg/cell}], monocytes/leukocytes >1.2*ULN [%]). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.	From start of study treatment up to 29-36 days after administration of last dose of study intervention (maximum up to 47 days)
Part 4: Number of Participants With Vital Signs Meeting Pre-Defined Criteria	Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value < 90 mmHg, change >= 30 mmHg increase, change >= 30 mmHg decrease; DBP: value < 50 mmHg, change >= 20 mmHg increase, change >= 20 mmHg decrease; PR: value < 40 bpm, value > 120 bpm.	Up to Day 11
Part 4: Number of Participants With ECG Abnormalities	Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.	Up to Day 11
Part 5: Number of Participants With TEAEs	An AE was any untoward medical occurrence in a participant temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE was considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were considered as TEAEs.	From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)
Part 5: Number of Participants With Laboratory Test Abnormalities	Laboratory parameters included: hematology (lymphocytes <0.8*LLN [10^3/mm3], lymphocytes/leukocytes <0.8*LLN [%], neutrophils/leukocytes <0.8*LLN [%], monocytes/leukocytes >1.2*ULN [%]), chemistry (amylase >1.5*ULN [units/liter] {U/L}), and urinalysis (urine hemoglobin >=1). Number of participants with any lab test abnormalities meeting the pre-specified criteria are reported in this outcome measure.	From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)
Part 5: Number of Participants With Vital Signs Meeting Pre-Defined Criteria	Vital signs including SBP, DBP and PR were measured in a supine position after approximately 5 minutes of rest for the participant. Criteria for vital signs included: SBP: value < 90 mmHg, change >= 30 mmHg increase, change >= 30 mmHg decrease; DBP: value < 50 mmHg, change >= 20 mmHg increase, change >= 20 mmHg decrease; PR: value < 40 bpm, value > 120 bpm.	From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)
Part 5: Number of Participants With ECG Abnormalities	Standard 12 lead ECGs were obtained with the participant in a supine position after at least 5 minutes of rest using an ECG machine that automatically calculated the heart rate and measured PR interval, QT interval, QTcF and QRS complex. Number of participants with abnormalities in ECG were reported in this outcome measure.	From start of study treatment up to 38-45 days after administration of last dose of study intervention (maximum up to 65 days)
Part 5: Time for Cmax (Tmax) of Midazolam	Tmax of midazolam was reported in this outcome measure.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm
Part 5: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Midazolam	AUClast of midazolam was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm
Part 5: Terminal Half-Life (t1/2) of Midazolam	t1/2 of midazolam was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm
Part 5: Apparent Clearance (CL/F) of Midazolam	CL/F of midazolam was reported in this outcome measure. CL/F was calculated as dose/AUCinf.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm
Part 5: Apparent Volume of Distribution (Vz/F) of Midazolam	Vz/F of midazolam was reported in this outcome measure. Vz/F was calculated as dose/(AUCinf*kel).	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for Midazolam 5 mg arm and Day 10 (pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 36, 48 hours post-dose) for PF-07817883 600 mg (Suspension) BID/ Midazolam 5 mg arm
Part 6: Maximum Observed Concentration (Cmax) of PF-07817883	Cmax of PF-07817883 was reported in this outcome measure.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)
Part 6: Time for Cmax (Tmax) of PF-07817883	Tmax of PF-07817883 was reported in this outcome measure.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)
Part 6: Area Under Plasma Concentration Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of PF-07817883	AUClast of PF-07817883 was reported in this outcome measure. AUClast was calculated by the linear/log trapezoidal method.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)
Part 6: Area Under the Concentration -Time Curve From Time Zero (0) Extrapolated to Infinite Time (AUCinf) of PF-07817883	AUCinf of PF-07817883 was reported in this outcome measure. AUCinf was calculated as AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)
Part 6: Terminal Half-Life (t1/2) of PF-07817883	t1/2 of PF-07817883 was reported in this outcome measure. t1/2 was calculated by Loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.	Day 1 (pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post-dose)

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2022
• Primary Completion (Actual): September 15, 2023
• Study Completion (Actual): September 15, 2023

Study Registration Dates

• First Submitted: October 11, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 14, 2022

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: September 12, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; Protease Inhibitor; Oral Antiviral; Mpro; PF-07817883
• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anesthetics; Central Nervous System Depressants; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Topoisomerase Inhibitors; Topoisomerase II Inhibitors; Moxifloxacin; Midazolam
• Other Study ID Numbers: C5091001; 2022-002871-12 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No