STUDY OF PF-07321332 IN HEALTHY PARTICIPANTS

Phase 1

Completed

• Conditions: Healthy Participants
• Interventions: 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); Drug: PF-07321332 Dose 1

• Registration Number: NCT04756531
• Lead Sponsor: Pfizer

Brief Summary

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.

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 Timeline

• Study Start: 2021-02-11
• Study First Submitted: 2021-02-11
• Study First Submitted QC: 2021-02-11
• Study First Posted: 2021-02-16
• Primary Completion: 2021-09-01
• Study Completion: 2021-09-01
• Results First Submitted: 2023-04-21
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-11
• Last Update Submitted: 2024-07-11
• Results First Posted: 2024-10-15
• Last Update Posted: 2024-10-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
PF-07321332 Dose 2	PF-07321332 Dose 2	Dose level 2 of PF-07321332
PF-07321332 Dose 3	PF-07321332 Dose 3	Dose level 3 of PF-07321332
PF-07321332 Dose 4	PF-07321332 Dose 4	Dose level 4 of PF-07321332
PF-07321332 Dose 5	PF-07321332 Dose 5	Dose level 5 of PF-07321332
PF-07321332 Dose 4 (Fed)	PF-07321332 Dose 4 or Placebo (Fed)	Dose level 4 of PF-07321332 with high fat meal
PF-07321332 Dose 1	PF-07321332 Dose 1	Dose level 1 of PF-07321332

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events (TEAEs) in PART-1: SAD	Post the single dose of study intervention till up to 36 days	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.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-1: SAD	Baseline up to Day 2 of the final period	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.
Number of Participants With Laboratory Abnormalities in PART-1: SAD	Baseline up to Day 4 of the final period	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.
Number of Participants With TEAEs in PART-2:MAD	Post first dose till up to 45 days after last dose of study intervention	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.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-2: MAD	Baseline up to Day 12	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.
Number of Participants With Laboratory Abnormalities in PART-2: MAD	Baseline up to Day 12	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.
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	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.
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	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	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.
Maximum Plasma Concentration (Cmax) of Tablet Formulation and Suspension in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	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.
Total Percent Recovery of Drug-Related Material in Urine in PART-4: ME	Day 1 to Day 11	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).
Total Percent Recovery of Drug-Related Material in Feces in PART-4: ME	Day 1 to Day 11	Total recovery of drug-related material excreted in feces, expressed as a percent of total dose administered, measured by 19F-NMR.
Total Percent Recovery of Drug-Related Material in Excreta (Urine and Feces Combined) in PART-4: ME	Day 1 to Day 11	Total recovery of drug-related material excreted in urine and feces combined, expressed as a percent of total dose administered, measured by 19F-NMR.
Number of Participants With TEAEs in PART-5: SE	Post first dose till up to 36 days after last dose of study intervention	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.
Number of Participants With Clinically Significant Change From Baseline in Vital Signs in PART-5: SE	Baseline up to Day 5 of the final period	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.
Number of Participants With Laboratory Abnormalities in PART-5: SE	Baseline up to Day 5 of the final period	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.

Secondary Outcome Measures

Name	Time	Method
Terminal Half-Life (t1/2) of Plasma PF-07321332 in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	t1/2 is the time measured for the plasma concentration of drug to decrease by one half of its initial concentration.
Cmax of Plasma PF-07321332 in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	Cmax is maximum plasma concentration. It was observed directly from data.
Time for Cmax (Tmax) of Plasma PF-07321332 in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	Time to reach Cmax.
AUClast of Plasma PF-07321332 in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.
AUCinf of PF-07321332 in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time.
Dose Normalized Cmax (Cmax[dn]) of Plasma PF-07321332 in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose.
Dose Normalized AUCinf (AUCinf[dn]) of Plasma PF-07321332 in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. AUCinf(dn) = AUCinf/dose.
Dose Normalized AUClast (AUClast[dn]) of Plasma PF-07321332 in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	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.
Apparent Volume of Distribution (Vz/F) in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	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.
Apparent Clearance (CL/F) in PART-1: SAD	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf.
Cmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10	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 is maximum plasma concentration. It was observed directly from data.
Tmax of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10	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.	Time to reach Cmax.
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	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.	AUCtau is area under the concentration-time profile from time 0 (pre-dose) to end of dosing interval, where dosing interval was 12 hours.
Cmax(dn) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10	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 is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose.
Dose Normalized AUCtau (AUCtau[dn]) of Plasma PF-07321332 in PART-2: MAD on Day 1, Day 5 and Day 10	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.	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.
Average Plasma Concentration Over the Dosing Interval (Cav) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	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.	Cav is average plasma concentration over the dosing interval, where dosing interval was 12 hours.
Minimum Observed Concentration During the Dosing Interval (Cmin) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	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.	Cmin is minimum observed concentration during the dosing interval, where dosing interval was 12 hours.
Observed Accumulation Ratio for AUCtau (Rac) Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	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.	Rac was calculated as Day 5 or Day 10 AUCtau/Day 1 AUCtau.
Observed Accumulation Ratio for Cmax (Rac,Cmax) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	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.	Rac,Cmax is Day 5 or Day 10 Cmax/Day 1 Cmax.
Peak-to-Trough Ratio (PTR) of Plasma PF-07321332 in PART-2: MAD on Day 5 and Day 10	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.	PTR is defined as peak-to-trough ratio. PTR = Cmax/Cmin.
CL/F of Plasma PF-07321332 in PART-2:MAD on Day 5 and Day 10	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 is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCtau.
Vz/F of Plasma PF-07321332 in PART-2: MAD on Day 10	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose 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.
t1/2 of of Plasma PF-07321332 in PART-2: MAD on Day 10	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose on Day 10.	t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.
Amount Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau) in PART-2: MAD on Day 10	Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16 hours post-dose 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.
CL/F of Plasma PF-07321332 in PART-4: ME	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf.
Percent of Dose Excreted in Urine as Unchanged Drug Over the Dosing Interval Tau (Aetau%) in PART-2: MAD on Day 10	Pre-dose to 12 hours post-dose 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.
Renal Clearance (CLr) in PART-2: MAD on Day 10	Pre-dose to 12 hours post-dose on Day 10	CLr is defined as the renal clearance. CLr = Aetau / AUCtau, where the dosing interval was 12 hours.
AUClast of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	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.
AUCinf of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	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.
Cmax of Plasma PF-07321332 of Tablet Formulation Under Fed Condition and Fasted Condition in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	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.
Cmax(dn) of Plasma PF-07321332 in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	Cmax is maximum plasma concentration. It was observed directly from data. Cmax(dn) = Cmax / dose.
Tmax of Plasma PF-07321332 in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	Time to reach Cmax.
AUClast(dn) of Plasma PF-07321332 in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	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.
AUCinf(dn) of Plasma PF-07321332 in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time. AUCinf(dn) = AUCinf/dose.
CL/F of Plasma PF-07321332 in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	CL/F is a quantitative measure of the rate at which a drug substance is removed from the blood. CL/F = Dose/AUCinf.
Vz/F of Plasma PF-07321332 in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	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.
t1/2 of Plasma PF-07321332 in PART-3: rBA/FE	Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 12, 16, 24, and 48 hours post-dose	t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.
Number of Participants With TEAEs in PART-3: rBA/FE	Post the single dose of study intervention till up to 36 days	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.
Number of Participants With Laboratory Test Abnormalities in PART-3: rBA/FE	Baseline up to Day 3	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.
Cmax of Plasma PF-07321332 in PART-4: ME	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	Cmax is maximum plasma concentration. It was observed directly from data.
Tmax of Plasma PF-07321332 in PART-4: ME	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	Tmax is time to reach Cmax.
AUClast of Plasma PF-07321332 in PART-4: ME	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.
AUCinf of Plasma PF-07321332 in PART-4: ME	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time.
Vz/F of Plasma PF-07321332 in PART-4: ME	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	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.
t1/2 of Plasma PF-07321332 in PART-4: ME	Pre-dose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose	t1/2 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.
Number of Participants With TEAEs in PART-4: ME	Post the single dose of study intervention till up to 36 days	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.
Number of Participants With Laboratory Abnormalities in PART-4: ME	Baseline up to Day 11	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.
Cmax of Plasma PF-07321332 in PART-5: SE	Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose	Cmax is maximum plasma concentration. It was observed directly from data.
Tmax of Plasma PF-07321332 in PART-5: SE	Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose	Time to reach Cmax.
AUClast of Plasma PF-07321332 in PART-5: SE	Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose	AUClast is area under the concentration-time profile from time 0 (pre-dose) to the time of the last quantifiable concentration.
AUCinf of Plasma PF-07321332 in PART-5: SE	Pre-dose, 1, 2, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96 hours post-dose	AUCinf is area under the concentration-time profile from time 0 (pre-dose) extrapolated to infinite time.
t1/2 of Plasma PF-07321332 in PART-5: SE	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 is the time measured for the plasma concentration of drug to decrease by one-half of its initial concentration.

Trial Locations

Locations (2)

Pfizer Clinical Research Unit - Brussels; 🇧🇪 Brussels, Bruxelles-capitale, Région DE, Belgium

New Haven Clinical Research Unit; 🇺🇸 New Haven, Connecticut, United States