Renal Impairment Study of PF-07321332 Boosted With Ritona... | NCT04909853

Status Module

Label	Type	Description	Intervention Names
PF-07321332	Experimental	PF 07321332/ritonavir	Drug: PF-07321332/ritonavir

Name	Type	Description	Arm Group Labels	Other Names
PF-07321332/ritonavir	Drug	PF-07321332 in combination with the PK boosting agent, ritonavir, being developed for the treatment of COVID-19	PF-07321332

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of PF-07321332		Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1
Area Under the Plasma Concentration-time Profile From Time Zero (0) to Extrapolated Infinite Time (AUCinf) of PF-07321332	AUCinf was calculated by AUClast + (Clast/kel). AUClast was the area under the plasma concentration-time profile from time 0 to the time of Clast. Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.	Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1
Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48)	Total amount of unchanged drug excreted in the urine over 48 hours.	Part 1 and Part 2: 0 to 48 hours post dose on Day 1
Renal Clearance (CLr) of PF-07321332	Renal clearance was calculated as total amount of unchanged drug excreted in the urine over 48 hours (Ae48) divided by area under the plasma concentration-time profile from time 0 to 48 hours post dose.	Part 1 and Part 2: 0 to 48 hours post dose on Day 1

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs	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. SAE was any untoward medical occurrence that, at any dose resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent was considered serious; other important medical events. TEAEs were events occurred following start of treatment or increased in severity up to maximum of 35 days after last dose. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness was judged by investigator.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female, non-smoker and/or light smoker
Have a diagnosis of stable renal impairment
Meet the following estimated glomerular filtration rate (eGFR) criteria during the screening period (based on 2 Screening visits) based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation:
- Mild renal impairment: eGFR between 60 - 89 mL/min.
- Moderate renal impairment: eGFR ≥30 mL/min and <60 mL/min.
- Severe renal impairment: eGFR <30 mL/min, but not requiring hemodialysis.
- Normal renal function: eGFR ≥90 mL/min

Renal impairment participants:

Any form of renal impairment except acute nephritic syndrome (participants with history of previous nephritic syndrome but in remission can be included).
Good general health commensurate with the population with chronic kidney disease (renal impairment).
Stable concomitant drug regimen for the management of individual participant's medical conditions, so long as they are considered necessary for the welfare of the study participants (eg, standard therapy for underlying diseases), and are not contraindicated with study drug, and are unlikely to interfere with the PK of study drug.

Healthy participants with normal renal function:

No clinically relevant abnormalities identified by a detailed medical history, full physical examination, including temperature, blood pressure (BP) and pulse rate measurement, 12 lead ECG and clinical laboratory tests.
Demographically comparable to the group of participants with impaired renal function.
- Each participant's body weight within ±15 kg of the mean body weight of renal impairment group.
- Each participant's age within ±10 years of the mean age of the renal impairment group.

Exclusion Criteria:

Positive test result for SARS-CoV-2 infection at the time of screening or Day -1.
History of HIV infection, hepatitis B, or hepatitis C; positive testing at screening for HIV, HBsAg, HBcAb, or HCVAb. As an exception a positive HBsAb test due to Hepatitis B vaccination is allowed.
Renal transplant recipients.
Urinary incontinence without catheterization
Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, cholecystectomy, appendectomy).
Participants who have been vaccinated with COVID-19 vaccines within the past 2 weeks of dosing, or are to be vaccinated with these vaccines at any time during the study.
A positive urine drug test, for illicit drugs, at Screening
aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >2 × upper limit of normal (ULN)
Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is≤ ULN.
History of sensitivity reactions to ritonavir or any of the formulation components of PF 07321332 or ritonavir.
Female participants of childbearing potential who are unwilling or unable to use highly effective methods of contraception as outlined in Section 5.3.4 for the duration of the study and for at least 28 days after the administration of investigational product, pregnant female participants, female participants planning to become pregnant during the duration of the study until 28 days after the administration of investigational product, breastfeeding female participants.

Renal impairment participants:

Participants requiring hemodialysis and/or peritoneal dialysis
Participants with other clinically significant disease that may affect the safety of the participant or that may affect the PK of PF-07321332. Participants with any significant hepatic, cardiac, or pulmonary disease or participants who are clinically nephrotic.

Healthy participants with normal renal function:

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
Screening supine BP >140 mm Hg (systolic) or >90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is >140 mm Hg (systolic) or >90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Orange County Research Center		Tustin	California	92780	United States
Investigational Drug Services (IDS) University of Miami Hospitals and Clinics

PubMed Identifier	Type	Citation	Retractions
35712797	Derived	Toussi SS, Neutel JM, Navarro J, Preston RA, Shi H, Kavetska O, LaBadie RR, Binks M, Chan PLS, Demers N, Corrigan B, Damle B. Pharmacokinetics of Oral Nirmatrelvir/Ritonavir, a Protease Inhibitor for Treatment of COVID-19, in Subjects With Renal Impairment. Clin Pharmacol Ther. 2022 Oct;112(4):892-900. doi: 10.1002/cpt.2688. Epub 2022 Jul 5.

Label	URL
To obtain contact information for a study center near you, click here.	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 milligram (mg) single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 8, 2021	Sep 20, 2022

Arm/Group Information

ID	Title	Description
BG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
BG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
BG002	Part 1: Moderate Renal Impairment	Participants with moderate renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
BG003	Part 2: Severe Renal Impairment	Participants with severe renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 2 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 2 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00010 BG0018 BG0028 BG0038 BG00434

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Observed Plasma Concentration (Cmax) of PF-07321332

The pharmacokinetic (PK) parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter

Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG002	Part 1: Moderate Renal Impairment	Participants with moderate renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG003	Part 2: Severe Renal Impairment	Participants with severe renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 2 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 2 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Units	Counts
Participants	OG00010 OG0018 OG0028 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001600± 31 OG0012077± 29 OG0022210± 17 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Ratio of Adjusted Geometric Means	129.78			2-Sided	90	101.93	165.25			Analysis used one-way ANOVA model with renal function as a fixed effect. The ratio of adjusted geometric means (test [impaired]/reference [normal]) and 90% confidence interval (CI) were expressed as percentages.		Other
OG000 OG002

Primary

Area Under the Plasma Concentration-time Profile From Time Zero (0) to Extrapolated Infinite Time (AUCinf) of PF-07321332

AUCinf was calculated by AUClast + (Clast/kel). AUClast was the area under the plasma concentration-time profile from time 0 to the time of Clast. Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest. Here, "Overall Number of Participants Analyzed" signifies number of participants who were evaluable for this outcome measure.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram*hour per milliliter

Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment

Primary

Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48)

Total amount of unchanged drug excreted in the urine over 48 hours.

The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

Milligram

Part 1 and Part 2: 0 to 48 hours post dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Primary

Renal Clearance (CLr) of PF-07321332

Renal clearance was calculated as total amount of unchanged drug excreted in the urine over 48 hours (Ae48) divided by area under the plasma concentration-time profile from time 0 to 48 hours post dose.

The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters per hour

Part 1 and Part 2: 0 to 48 hours post dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs

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. SAE was any untoward medical occurrence that, at any dose resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was a suspected transmission via a Pfizer product of an infectious agent was considered serious; other important medical events. TEAEs were events occurred following start of treatment or increased in severity up to maximum of 35 days after last dose. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness was judged by investigator.

Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Number of Participants With Clinical Laboratory Abnormalities

The hematology, clinical chemistry and urinalysis tests were included in the laboratory examination. The criteria for hematology evaluation included hemoglobin less than (<) 0.8*lower limit of normal (LLN), hematocrit <0.8*LLN, erythrocytes <0.8*LLN, erythrocyte mean corpuscular hemoglobin <0.9*LLN and lymphocytes <0.8*LLN. The criteria for clinical chemistry evaluation included neutrophils <0.8*LLN, eosinophils greater than (>) 1.2* upper limit of normal (ULN), monocytes >1.2*ULN, urea nitrogen >1.3*ULN, creatinine >1.3*ULN, urate >1.2*ULN, potassium >1.1*ULN and bicarbonate <0.9*LLN. The criteria for urinalysis evaluation included thyrotropin >1.2*ULN, glucose >1.5*ULN, fibrinogen >1.25*baseline, ketones greater than or equal to (>=) 1, urine protein >=1, nitrite >=1 and leukocyte esterase >=1.

Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Number of Participants With Clinically Significant Vital Signs Abnormalities

Supine blood pressure, pulse rate, respiratory rate and oral temperature were evaluated in vital signs examination. Clinical significance was judged by investigator.

Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Number of Participants With Clinically Significant Findings in Physical Examination

A complete physical examination included, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. Clinical significance was judged by investigator.

Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities

A standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) were collected using an ECG machine that automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. Clinical significance was judged by investigator.

Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Posted

Count of Participants

Participants

Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Plasma Concentration of PF-07321332 at 12 Hours Post Dose (C12)

The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter

Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours post-dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Plasma Concentration of PF-07321332 at 24 Hours Post Dose (C24)

The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram per milliliter

Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332

Tmax was observed directly from data as time of first occurrence.

The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.

Posted

Median

Full Range

Hours

Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Area Under the Plasma Concentration-time Profile From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of PF-07321332

Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration was determined by linear/log trapezoidal method.

The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.

Posted

Geometric Mean

Geometric Coefficient of Variation

Nanogram*hour per milliliter

Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Secondary

Apparent Clearance (CL/F) of PF-07321332 From Plasma

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma. CL/F was calculated by Dose/AUCinf.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters per hour

Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment

Secondary

Apparent Volume of Distribution (Vz/F) of PF-07321332

Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. Vz/F was calculated by dose/(AUCinf*kel). kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Posted

Geometric Mean

Geometric Coefficient of Variation

Liters

Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment

Secondary

Terminal Elimination Plasma Half-life (t1/2) of PF-07321332

t1/2 was calculated by Loge(2)/kel. kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

Posted

Mean

Standard Deviation

Hours

Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1

ID	Title	Description
OG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.
OG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1: Normal Renal Function	Participants with normal renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.	10	0	10	2	10
EG001	Part 1: Mild Renal Impairment	Participants with mild renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.	8	0	8	1	8
EG002	Part 1: Moderate Renal Impairment	Participants with moderate renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 1 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 1 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.	8	0	8	1	8
EG003	Part 2: Severe Renal Impairment	Participants with severe renal function received PF-07321332 100 mg single oral dose on Day 1 of Part 2 of the study. Participants were administered with pharmacokinetic boosting agent ritonavir 100 mg orally on Day -1 at -12 hours, Day 1 at 0 hours and 12 hours, and Day 2 at 24 hours, relative to PF-07321332 dosing in Part 2 of the study. Participants were followed-up to maximum of 35 days after the last administration of ritonavir or from the time of early termination/discontinuation.	8	1	8	5	8

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG0031 affected8 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Asthenia	General disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Headache	Nervous system disorders	MedDRA 24.0	Non-systematic Assessment	EG0002 affected10 at risk EG0010 affected8 at risk EG0021 affected8 at risk EG003
Agitation	Psychiatric disorders	MedDRA 24.0	Non-systematic Assessment	EG0001 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0011 affected8 at risk EG0020 affected8 at risk EG003
Hypotension	Vascular disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003

ID	Term
D007674	Kidney Diseases
D014570	Urologic Diseases
D052776	Female Urogenital Diseases
D005261	Female Urogenital Diseases and Pregnancy Complications
D000091642	Urogenital Diseases
D052801	Male Urogenital Diseases
D011024	Pneumonia, Viral
D011014	Pneumonia
D012141	Respiratory Tract Infections
D007239	Infections
D014777	Virus Diseases
D018352	Coronavirus Infections
D003333	Coronaviridae Infections
D030341	Nidovirales Infections
D012327	RNA Virus Infections
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
C000719967	nirmatrelvir and ritonavir drug combination
C000718217	nirmatrelvir

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pneumonia	Infections and infestations	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG0031 affected8 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 24.0	Non-systematic Assessment	EG0000 affected10 at risk EG0010 affected8 at risk EG0020 affected8 at risk EG003