Renal Impairment
Conditions
Keywords
SARS-CoV-2, COVID-19
Brief summary
This is a Phase 1, non-randomized, open-label, 2-part study to investigate the effect of renal impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose of PF-07321332 in combination with the PK boosting agent ritonavir. Participants will be selected and categorized into normal renal function or renal impairment groups based on their estimated glomerular filtration rate. Part 1: will be conducted in approximately 24 participants (approximately 8 per group) with stable mild or moderate renal impairment and a control group of participants with normal renal function. Part 2 will be conducted in approximately 8 participants with stable severe renal impairment.
Interventions
PF-07321332 in combination with the PK boosting agent, ritonavir, being developed for the treatment of COVID-19
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | 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. |
| Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48) | Part 1 and Part 2: 0 to 48 hours post dose on Day 1 | Total amount of unchanged drug excreted in the urine over 48 hours. |
| Renal Clearance (CLr) of PF-07321332 | Part 1 and Part 2: 0 to 48 hours post dose on Day 1 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities | Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days) | 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. |
| Plasma Concentration of PF-07321332 at 12 Hours Post Dose (C12) | 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 | — |
| Plasma Concentration of PF-07321332 at 24 Hours Post Dose (C24) | 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 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) 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 | Tmax was observed directly from data as time of first occurrence. |
| 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 | Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 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. 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. |
| Apparent Clearance (CL/F) of PF-07321332 From Plasma | 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 | 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. |
| Apparent Volume of Distribution (Vz/F) 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 | 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. |
| Terminal Elimination Plasma Half-life (t1/2) 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 | 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. |
| Area Under the Plasma Concentration-time Profile From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) 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 0 to the time of the last quantifiable concentration was determined by linear/log trapezoidal method. |
| Number of Participants With Clinical Laboratory Abnormalities | Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days) | 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. |
| Number of Participants With Clinically Significant Vital Signs Abnormalities | Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days) | Supine blood pressure, pulse rate, respiratory rate and oral temperature were evaluated in vital signs examination. Clinical significance was judged by investigator. |
| Number of Participants With Clinically Significant Findings in Physical Examination | Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days) | 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. |
Countries
United States
Participant flow
Recruitment details
Study had 2 parts, Part 1 and 2. Enrollment were separate for both the parts. A total of 35 participants (27 in Part 1 and 8 in Part 2) were enrolled in the study of which 34 participants received the study treatment.
Pre-assignment details
Participants were grouped on the basis of severity of renal impairment. Severity was evaluated using estimated glomerular filtration rate (eGFR) in milliliter per minute (mL/min) based on chronic kidney disease-epidemiology collaboration (CKD-EPI) formula. Following were the classifications, a) Normal: eGFR greater than or equal to (\>=) 90 mL/min, b) Mild: eGFR 60 to less than (\<) 90 mL/min, c) Moderate: eGFR \>= 30 to \<60 mL/min and d) Severe: eGFR \<30 mL/min and not requiring dialysis.
Participants by arm
| Arm | Count |
|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part 1 | Assigned but not treated | 0 | 0 | 1 | 0 |
| Part 2 | Adverse Event | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: Mild Renal Impairment | Part 1: Moderate Renal Impairment | Part 2: Severe Renal Impairment | Total | Part 1: Normal Renal Function |
|---|---|---|---|---|---|
| Age, Continuous | 63.8 Years STANDARD_DEVIATION 9.07 | 62.0 Years STANDARD_DEVIATION 8.57 | 62.1 Years STANDARD_DEVIATION 9.46 | 62.2 Years STANDARD_DEVIATION 7.45 | 61.1 Years STANDARD_DEVIATION 3.03 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 4 Participants | 9 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 8 Participants | 4 Participants | 25 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 6 Participants | 2 Participants | 12 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 2 Participants | 6 Participants | 21 Participants | 7 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 2 Participants | 11 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 5 Participants | 6 Participants | 23 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 2 / 10 | 1 / 8 | 1 / 8 | 5 / 8 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 | 0 / 8 | 1 / 8 |
Outcome results
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.
Time frame: Part 1 and Part 2: 0 to 48 hours post dose on Day 1
Population: The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48) | 31.20 Milligram | Geometric Coefficient of Variation 45 |
| Part 1: Mild Renal Impairment | Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48) | 42.65 Milligram | Geometric Coefficient of Variation 23 |
| Part 1: Moderate Renal Impairment | Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48) | 30.83 Milligram | Geometric Coefficient of Variation 56 |
| Part 2: Severe Renal Impairment | Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48) | 18.46 Milligram | Geometric Coefficient of Variation 50 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Area Under the Plasma Concentration-time Profile From Time Zero (0) to Extrapolated Infinite Time (AUCinf) of PF-07321332 | 14460 Nanogram*hour per milliliter | Geometric Coefficient of Variation 20 |
| Part 1: Mild Renal Impairment | Area Under the Plasma Concentration-time Profile From Time Zero (0) to Extrapolated Infinite Time (AUCinf) of PF-07321332 | 17910 Nanogram*hour per milliliter | Geometric Coefficient of Variation 30 |
| Part 1: Moderate Renal Impairment | Area Under the Plasma Concentration-time Profile From Time Zero (0) to Extrapolated Infinite Time (AUCinf) of PF-07321332 | 27110 Nanogram*hour per milliliter | Geometric Coefficient of Variation 27 |
| Part 2: Severe Renal Impairment | Area Under the Plasma Concentration-time Profile From Time Zero (0) to Extrapolated Infinite Time (AUCinf) of PF-07321332 | 44040 Nanogram*hour per milliliter | Geometric Coefficient of Variation 33 |
90% CI: [99.64, 153.91]
90% CI: [148.52, 236.46]
90% CI: [237.6, 390.21]
Primary
Maximum Observed Plasma Concentration (Cmax) of PF-07321332
Time frame: 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
Population: The pharmacokinetic (PK) parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Maximum Observed Plasma Concentration (Cmax) of PF-07321332 | 1600 Nanogram per milliliter | Geometric Coefficient of Variation 31 |
| Part 1: Mild Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of PF-07321332 | 2077 Nanogram per milliliter | Geometric Coefficient of Variation 29 |
| Part 1: Moderate Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of PF-07321332 | 2210 Nanogram per milliliter | Geometric Coefficient of Variation 17 |
| Part 2: Severe Renal Impairment | Maximum Observed Plasma Concentration (Cmax) of PF-07321332 | 2369 Nanogram per milliliter | Geometric Coefficient of Variation 38 |
90% CI: [101.93, 165.25]
90% CI: [113.18, 168.55]
90% CI: [111.4, 196.68]
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.
Time frame: Part 1 and Part 2: 0 to 48 hours post dose on Day 1
Population: The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Renal Clearance (CLr) of PF-07321332 | 2.180 Liters per hour | Geometric Coefficient of Variation 50 |
| Part 1: Mild Renal Impairment | Renal Clearance (CLr) of PF-07321332 | 2.395 Liters per hour | Geometric Coefficient of Variation 33 |
| Part 1: Moderate Renal Impairment | Renal Clearance (CLr) of PF-07321332 | 1.154 Liters per hour | Geometric Coefficient of Variation 71 |
| Part 2: Severe Renal Impairment | Renal Clearance (CLr) of PF-07321332 | 0.4398 Liters per hour | Geometric Coefficient of Variation 73 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Apparent Clearance (CL/F) of PF-07321332 From Plasma | 6.913 Liters per hour | Geometric Coefficient of Variation 20 |
| Part 1: Mild Renal Impairment | Apparent Clearance (CL/F) of PF-07321332 From Plasma | 5.581 Liters per hour | Geometric Coefficient of Variation 30 |
| Part 1: Moderate Renal Impairment | Apparent Clearance (CL/F) of PF-07321332 From Plasma | 3.689 Liters per hour | Geometric Coefficient of Variation 27 |
| Part 2: Severe Renal Impairment | Apparent Clearance (CL/F) of PF-07321332 From Plasma | 2.270 Liters per hour | Geometric Coefficient of Variation 33 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Apparent Volume of Distribution (Vz/F) of PF-07321332 | 74.95 Liters | Geometric Coefficient of Variation 35 |
| Part 1: Mild Renal Impairment | Apparent Volume of Distribution (Vz/F) of PF-07321332 | 51.95 Liters | Geometric Coefficient of Variation 32 |
| Part 1: Moderate Renal Impairment | Apparent Volume of Distribution (Vz/F) of PF-07321332 | 50.34 Liters | Geometric Coefficient of Variation 27 |
| Part 2: Severe Renal Impairment | Apparent Volume of Distribution (Vz/F) of PF-07321332 | 42.73 Liters | Geometric Coefficient of Variation 26 |
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.
Time frame: 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
Population: The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Area Under the Plasma Concentration-time Profile From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of PF-07321332 | 14270 Nanogram*hour per milliliter | Geometric Coefficient of Variation 20 |
| Part 1: Mild Renal Impairment | Area Under the Plasma Concentration-time Profile From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of PF-07321332 | 17770 Nanogram*hour per milliliter | Geometric Coefficient of Variation 30 |
| Part 1: Moderate Renal Impairment | Area Under the Plasma Concentration-time Profile From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of PF-07321332 | 26660 Nanogram*hour per milliliter | Geometric Coefficient of Variation 21 |
| Part 2: Severe Renal Impairment | Area Under the Plasma Concentration-time Profile From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of PF-07321332 | 39420 Nanogram*hour per milliliter | Geometric Coefficient of Variation 28 |
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.
Time frame: Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Normal Renal Function | Number of Participants With Clinical Laboratory Abnormalities | 5 Participants |
| Part 1: Mild Renal Impairment | Number of Participants With Clinical Laboratory Abnormalities | 4 Participants |
| Part 1: Moderate Renal Impairment | Number of Participants With Clinical Laboratory Abnormalities | 8 Participants |
| Part 2: Severe Renal Impairment | Number of Participants With Clinical Laboratory Abnormalities | 8 Participants |
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.
Time frame: Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Normal Renal Function | Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Part 1: Mild Renal Impairment | Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Part 1: Moderate Renal Impairment | Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities | 0 Participants |
| Part 2: Severe Renal Impairment | Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities | 1 Participants |
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.
Time frame: Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Normal Renal Function | Number of Participants With Clinically Significant Findings in Physical Examination | 0 Participants |
| Part 1: Mild Renal Impairment | Number of Participants With Clinically Significant Findings in Physical Examination | 1 Participants |
| Part 1: Moderate Renal Impairment | Number of Participants With Clinically Significant Findings in Physical Examination | 0 Participants |
| Part 2: Severe Renal Impairment | Number of Participants With Clinically Significant Findings in Physical Examination | 0 Participants |
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.
Time frame: Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Normal Renal Function | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
| Part 1: Mild Renal Impairment | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
| Part 1: Moderate Renal Impairment | Number of Participants With Clinically Significant Vital Signs Abnormalities | 0 Participants |
| Part 2: Severe Renal Impairment | Number of Participants With Clinically Significant Vital Signs Abnormalities | 1 Participants |
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.
Time frame: Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)
Population: Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Normal Renal Function | 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 | TEAEs | 2 Participants |
| Part 1: Normal Renal Function | 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 | Treatment Emergent SAEs | 0 Participants |
| Part 1: Normal Renal Function | 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 | Treatment-related AEs | 0 Participants |
| Part 1: Normal Renal Function | 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 | Treatment-related SAEs | 0 Participants |
| Part 1: Mild Renal Impairment | 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 | Treatment Emergent SAEs | 0 Participants |
| Part 1: Mild Renal Impairment | 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 | Treatment-related AEs | 0 Participants |
| Part 1: Mild Renal Impairment | 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 | Treatment-related SAEs | 0 Participants |
| Part 1: Mild Renal Impairment | 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 | TEAEs | 1 Participants |
| Part 1: Moderate Renal Impairment | 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 | Treatment-related AEs | 0 Participants |
| Part 1: Moderate Renal Impairment | 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 | Treatment Emergent SAEs | 0 Participants |
| Part 1: Moderate Renal Impairment | 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 | Treatment-related SAEs | 0 Participants |
| Part 1: Moderate Renal Impairment | 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 | TEAEs | 1 Participants |
| Part 2: Severe Renal Impairment | 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 | Treatment-related SAEs | 0 Participants |
| Part 2: Severe Renal Impairment | 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 | Treatment Emergent SAEs | 1 Participants |
| Part 2: Severe Renal Impairment | 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 | TEAEs | 5 Participants |
| Part 2: Severe Renal Impairment | 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 | Treatment-related AEs | 2 Participants |
Secondary
Plasma Concentration of PF-07321332 at 12 Hours Post Dose (C12)
Time frame: 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
Population: The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Plasma Concentration of PF-07321332 at 12 Hours Post Dose (C12) | 341.9 Nanogram per milliliter | Geometric Coefficient of Variation 35 |
| Part 1: Mild Renal Impairment | Plasma Concentration of PF-07321332 at 12 Hours Post Dose (C12) | 438.0 Nanogram per milliliter | Geometric Coefficient of Variation 30 |
| Part 1: Moderate Renal Impairment | Plasma Concentration of PF-07321332 at 12 Hours Post Dose (C12) | 785.6 Nanogram per milliliter | Geometric Coefficient of Variation 33 |
| Part 2: Severe Renal Impairment | Plasma Concentration of PF-07321332 at 12 Hours Post Dose (C12) | 1213 Nanogram per milliliter | Geometric Coefficient of Variation 33 |
Secondary
Plasma Concentration of PF-07321332 at 24 Hours Post Dose (C24)
Time frame: 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
Population: The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Plasma Concentration of PF-07321332 at 24 Hours Post Dose (C24) | 99.10 Nanogram per milliliter | Geometric Coefficient of Variation 35 |
| Part 1: Mild Renal Impairment | Plasma Concentration of PF-07321332 at 24 Hours Post Dose (C24) | 112.8 Nanogram per milliliter | Geometric Coefficient of Variation 55 |
| Part 1: Moderate Renal Impairment | Plasma Concentration of PF-07321332 at 24 Hours Post Dose (C24) | 179.1 Nanogram per milliliter | Geometric Coefficient of Variation 108 |
| Part 2: Severe Renal Impairment | Plasma Concentration of PF-07321332 at 24 Hours Post Dose (C24) | 694.2 Nanogram per milliliter | Geometric Coefficient of Variation 42 |
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Normal Renal Function | Terminal Elimination Plasma Half-life (t1/2) of PF-07321332 | 7.725 Hours | Standard Deviation 1.8234 |
| Part 1: Mild Renal Impairment | Terminal Elimination Plasma Half-life (t1/2) of PF-07321332 | 6.606 Hours | Standard Deviation 1.5344 |
| Part 1: Moderate Renal Impairment | Terminal Elimination Plasma Half-life (t1/2) of PF-07321332 | 9.948 Hours | Standard Deviation 3.4171 |
| Part 2: Severe Renal Impairment | Terminal Elimination Plasma Half-life (t1/2) of PF-07321332 | 13.37 Hours | Standard Deviation 3.3225 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332
Tmax was observed directly from data as time of first occurrence.
Time frame: 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
Population: The PK parameter analysis population included all participants dosed who had at least 1 of the PK parameters of primary interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Normal Renal Function | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332 | 2.000 Hours |
| Part 1: Mild Renal Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332 | 2.000 Hours |
| Part 1: Moderate Renal Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332 | 2.500 Hours |
| Part 2: Severe Renal Impairment | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332 | 3.000 Hours |