STUDY OF PF-07321332 IN HEALTHY PARTICIPANTS

A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO CONTROLLED, SINGLE- AND MULTIPLE-DOSE ESCALATION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF PF 07321332 IN HEALTHY ADULT PARTICIPANTS

A Phase 1, double blind, sponsor open, single and multiple ascending dose study to evaluate safety, tolerability and pharmacokinetics of PF-07321332 in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: PF-07321332 Dose 1; Drug: PF-07321332 Dose 2; Drug: PF-07321332 Dose 3; Drug: PF-07321332 Dose 4; Drug: PF-07321332 Dose 5; Drug: PF-07321332 Dose 4 or Placebo (Fed)

Detailed Description

Combined 5-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: Supra-therapeutic Exposure Part-1,2 and 5 are double blind, sponsor open and Part-3 and 4 are open label study.

• Study Type: Interventional
• Enrollment (Actual): 70
• 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: 14 years to 56 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)
• Japanese subjects who have four Japanese biologic grandparents born in Japan

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-07321332 Dose 1; Dose level 1 of PF-07321332	Drug: PF-07321332 Dose 1; PF-07321332 Dose 1 or Placebo
Experimental: PF-07321332 Dose 2; Dose level 2 of PF-07321332	Drug: PF-07321332 Dose 2; PF-07321332 Dose 2 or Placebo
Experimental: PF-07321332 Dose 3; Dose level 3 of PF-07321332	Drug: PF-07321332 Dose 3; PF-07321332 Dose 3 or Placebo
Experimental: PF-07321332 Dose 4; Dose level 4 of PF-07321332	Drug: PF-07321332 Dose 4; PF-07321332 Dose 4 or Placebo
Experimental: PF-07321332 Dose 5; Dose level 5 of PF-07321332	Drug: PF-07321332 Dose 5; PF-07321332 Dose 5 or Placebo
Experimental: PF-07321332 Dose 4 (Fed); Dose level 4 of PF-07321332 with high fat meal	Drug: PF-07321332 Dose 4 or Placebo (Fed); PF-07321332 Dose 5 or Placebo with high fat meal

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD	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. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.	Post the single dose of study intervention till up to 36 days
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD	Vital signs (temperature, respiratory rate, pulse rate [PR], systolic blood pressure [SBP], and diastolic blood pressure [DBP]) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value <50 millimeters of mercury (mm Hg), increase >=20 mm Hg, or decrease >=20 mm Hg; PR: value <40 beats per minute (bpm) or value >120 bpm; SBP: value <90 mm Hg, increase >=30 mm Hg, or decrease >=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of study intervention and had at least 1 assessment undertaken post treatment.	Baseline up to Day 2 of the final period
Number of Participants With Laboratory Abnormalities in PART-1: SAD	Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, Severe Acute Respiratory Syndrome Coronavirus 2 [SARS-CoV-2] reverse transcription polymerase chain reaction [RT-PCR], estimated glomerular filtration rate [eGFR], pregnancy test [beta human chorionic gonadotropin [b-hCG]], activated partial thromboplastin time [aPTT], prothrombin time [PT] - international normalized ratio [INR], fibrinogen, thyroid stimulating hormone [TSH], Free thyroxine [T4]). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.	Baseline up to Day 4 of the final period
Number of Participants With TEAEs in PART-2:MAD	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. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.	Post first dose till up to 45 days after last dose of study intervention
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD	Vital signs (temperature, respiratory rate, PR, SBP, DBP) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value <50 mm Hg, increase >=20 mm Hg, or decrease >=20 mm Hg; PR: value <40 bpm or value >120 bpm; SBP: value <90 mm Hg, increase >=30 mm Hg, or decrease >=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion.	Baseline up to Day 12
Number of Participants With Laboratory Abnormalities in PART-2: MAD	Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test [b-hCG], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.	Baseline up to Day 12
Area Under the Plasma Concentration-Time Profile From Time 0 to The Time of The Last Quantifiable Concentration (AUClast) of Tablet Formulation and Suspension in PART-3: rBA/FE	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Tablet Formulation and Suspension in PART-3: rBA/FE	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. Natural log transformed AUCinf for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test [tablet] /Reference [suspension]) and 90% CI for the ratio.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Maximum Plasma Concentration (Cmax) of Tablet Formulation and Suspension in PART-3: rBA/FE	Cmax is maximum plasma concentration. It was observed directly from data. Natural log transformed Cmax for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test [tablet] /Reference [suspension]) and 90% CI for the ratio.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Total Percent Recovery of Drug-Related Material in Urine in PART-4: ME	Total recovery of drug-related material excreted in urine, expressed as a percent of total dose administered, measured by fluorine-19 nuclear magnetic resonance (19F-NMR).	Day 1 to Day 11
Total Percent Recovery of Drug-Related Material in Feces in PART-4: ME	Total recovery of drug-related material excreted in feces, expressed as a percent of total dose administered, measured by 19F-NMR.	Day 1 to Day 11
Total Percent Recovery of Drug-Related Material in Excreta (Urine and Feces Combined) in PART-4: ME	Total recovery of drug-related material excreted in urine and feces combined, expressed as a percent of total dose administered, measured by 19F-NMR.	Day 1 to Day 11
Number of Participants With TEAEs in PART-5: SE	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. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.	Post first dose till up to 36 days after last dose of study intervention
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE	Vital signs (temperature, respiratory rate, PR, SBP, DBP) were obtained with participants following at least 5 minutes of supine rest. Categorical criteria were defined as DBP: value <50 mm Hg, increase >=20 mm Hg, or decrease >=20 mm Hg; PR: value <40 bpm or value >120 bpm; SBP: value <90 mm Hg, increase >=30 mm Hg, or decrease >=30 mm Hg. Clinical significance of vital signs was determined at the investigator's discretion.	Baseline up to Day 5 of the final period
Number of Participants With Laboratory Abnormalities in PART-5: SE	Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test [b-hCG], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.	Baseline up to Day 5 of the final period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of Plasma PF-07321332 in PART-1: SAD	Cmax is maximum plasma concentration. It was observed directly from data.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD	Time to reach Cmax.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
AUClast of Plasma PF-07321332 in PART-1: SAD	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
AUCinf of PF-07321332 in PART-1: SAD	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD	Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. AUCinf(dn) = AUCinf/dose.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. AUClast(dn) = AUClast /dose.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Apparent Volume of Distribution (Vz/F) in PART-1: SAD	Vz/F = Dose/(AUCinf*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Apparent Clearance (CL/F) in PART-1: SAD	CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD	t1/2 is the time measured for the plasma concentration of drug to decrease by one half of its initial concentration.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10	Cmax is maximum plasma concentration. It was observed directly from data.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10	Time to reach Cmax.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Area Under the Plasma Concentration Time Profile From Time 0 to Time Tau (AUCtau) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10	AUCtau is area under the concentration-time profile from time 0 (pre-dose) to end of dosing interval, where dosing interval was 12 hours.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10	Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10	AUCtau is area under the concentration-time profile from time 0 (pre-dose) to end of dosing interval, where dosing interval was 12 hours. AUCtau(dn) = AUCtau/dose.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	Cav is average plasma concentration over the dosing interval, where dosing interval was 12 hours.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	Cmin is minimum observed concentration during the dosing interval, where dosing interval was 12 hours.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	Rac was calculated as Day 5 or Day 10 AUCtau/Day 1 AUCtau.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	Rac,Cmax is Day 5 or Day 10 Cmax/Day 1 Cmax.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	PTR is defined as peak-to-trough ratio. PTR = Cmax/Cmin.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10	CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCtau.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours post-dose on Day 1, Day 5; and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Vz/F of Plasma PF-07321332 in PART-2: MAD on Day 10	Vz/F 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. Vz/F = Dose/(AUCinf*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
t1/2 of of Plasma PF-07321332 in PART-2: MAD on Day 10	t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) in PART-2: MAD on Day 10	Ae is the cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval is 12 hours. Aetau is the sum of (urine volume × urine concentration) for each collection over the dosing interval.	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.
Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) in PART-2: MAD on Day 10	Aetau% is defined as percent of dose excreted in urine as unchanged drug over the dosing interval, where the dosing interval is 12 hours. Aetau% = Aetau / Dose * 100.	Pre-dose to 12 hours post-dose on Day 10
Renal Clearance (CLr) in PART-2: MAD on Day 10	CLr is defined as the renal clearance. CLr = Aetau / AUCtau, where the dosing interval was 12 hours.	Pre-dose to 12 hours post-dose on Day 10
AUClast of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. Natural log transformed AUClast for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test [tablet under fed condition] /Reference [tablet under fasted condition]) and 90% CI for the ratio.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
AUCinf of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. Natural log transformed AUCinf for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test [tablet under fed condition] /Reference [tablet under fasted condition]) and 90% CI for the ratio.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Cmax of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE	Cmax is maximum plasma concentration. It was observed directly from data. Natural log transformed Cmax for PF-07321332 was analyzed to provide an estimate of the ratio of adjusted geometric means (Test [tablet under fed condition] /Reference [tablet under fasted condition]) and 90% CI for the ratio.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Cmax(dn) of Plasma PF-07321332 in PART-3: rBA/FE	Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Tmax of Plasma PF-07321332 in PART-3: rBA/FE	Time to reach Cmax.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
AUClast(dn) of Plasma PF-07321332 in PART-3: rBA/FE	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration. AUClast(dn) = AUClast /dose.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
AUCinf(dn) of Plasma PF-07321332 in PART-3: rBA/FE	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. AUCinf(dn) = AUCinf/dose.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
CL/F of Plasma PF-07321332 in PART-3: rBA/FE	CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Vz/F of Plasma PF-07321332 in PART-3: rBA/FE	Vz/F = Dose/(AUCinf*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
t1/2 of Plasma PF-07321332 in PART-3: rBA/FE	t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose
Number of Participants With TEAEs in PART-3: rBA/FE	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. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.	Post the single dose of study intervention till up to 36 days
Number of Participants With Laboratory Test Abnormalities in PART-3: rBA/FE	Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test [b-hCG], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion. The analysis population included all participants who received at least 1 dose of the study intervention.	Baseline up to Day 3
Cmax of Plasma PF-07321332 in PART-4: ME	Cmax is maximum plasma concentration. It was observed directly from data.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Tmax of Plasma PF-07321332 in PART-4: ME	Tmax is time to reach Cmax.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
AUClast of Plasma PF-07321332 in PART-4: ME	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
AUCinf of Plasma PF-07321332 in PART-4: ME	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
CL/F of Plasma PF-07321332 in PART-4: ME	CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Vz/F of Plasma PF-07321332 in PART-4: ME	Vz/F = Dose/(AUCinf*kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
t1/2 of Plasma PF-07321332 in PART-4: ME	t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose
Number of Participants With TEAEs in PART-4: ME	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. TEAEs were those with initial onset or increasing in severity between the first dose of study intervention and up to 36 days after last dose of study intervention. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. SAEs were adjudicated according to the investigator's assessment. Treatment-related AEs and SAEs were determined by the investigator.	Post the single dose of study intervention till up to 36 days
Number of Participants With Laboratory Abnormalities in PART-4: ME	Laboratory parameters included hematology, chemistry, urinalysis, and other (urine drug screening, SARS-CoV-2 RT-PCR, eGFR, pregnancy test [b-hCG], aPTT, PT-INR, fibrinogen, TSH, Free T4). The clinical significance of laboratory parameters was determined at the investigator's discretion.	Baseline up to Day 11
Cmax of Plasma PF-07321332 in PART-5: SE	Cmax is maximum plasma concentration. It was observed directly from data.	Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
Tmax of Plasma PF-07321332 in PART-5: SE	Time to reach Cmax.	Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
AUClast of Plasma PF-07321332 in PART-5: SE	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.	Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
AUCinf of Plasma PF-07321332 in PART-5: SE	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time.	Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose
t1/2 of Plasma PF-07321332 in PART-5: SE	t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.	Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Singh RSP, Toussi SS, Hackman F, Chan PL, Rao R, Allen R, Van Eyck L, Pawlak S, Kadar EP, Clark F, Shi H, Anderson AS, Binks M, Menon S, Nucci G, Bergman A. Innovative Randomized Phase I Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir. Clin Pharmacol Ther. 2022 Jul;112(1):101-111. doi: 10.1002/cpt.2603. Epub 2022 May 4.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2021
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): September 1, 2021

Study Registration Dates

• First Submitted: February 11, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Protease Inhibitors; Viral Protease Inhibitors; Nirmatrelvir
• Other Study ID Numbers: C4671001; 2020-006073-30 (EudraCT Number)

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