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The study is to estimate the effect of hepatic impairment on the plasma PK of PF-07321332/ritonavir. Findings from this study will be used to develop dosing recommendations so that the dose and/or dosing interval may be adjusted appropriately in the presence of hepatic impairment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1 | Experimental | Healthy Volunteer |
|
| Cohort 2 | Experimental | Hepatic Impairment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-07321332 | Drug | Tablet |
| |
| Ritonavir |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Plasma PF-07321332 | Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation was expressed in percentage. | Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours |
| Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-07321332 | AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation was expressed in percentage. | Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours |
| Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-07321332 | AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation was expressed in percentage. | Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With an Treatment Emergent Adverse Event (TEAE) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. |
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Inclusion Criteria:
Exclusion Criteria:
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| 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 | ||
| Prism Research LLC dba Nucleus Network |
Not provided
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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Seventeen participants were assigned to treatment. One participant in the moderate hepatic impairment group was excluded from the safety and pharmacokinetic (PK) analysis set as this participant was randomized but was discontinued on Day 1 prior to dosing with study treatment PF-07321332. All 16 treated participants included 8 participants without hepatic impairment (Cohort 1) and 8 participants with moderate hepatic impairment (Cohort 2) completed the study.,
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| ID | Title | Description |
|---|---|---|
| FG000 | Normal Hepatic Function | Participants with normal hepatic function and matched, by average age, weight, and gender as much as practically possible with participants with moderate hepatic impairment. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing. |
| FG001 | Moderate Hepatic Impairment | Moderate Hepatic Impairment: Participants with moderate hepatic impairment (grade B) with a Child-Pugh Score of 7-9. The CP classification assesses 5 hepatic parameters (serum total bilirubin, serum albumin, prothrombin time prolongation, ascites, and encephalopathy grade) on a scale of 1 to 3 (most severe derangement). Total moderate hepatic impairment score range is 7 to 9. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
All enrolled participants who received at least one dose of study intervention.
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| ID | Title | Description |
|---|---|---|
| BG000 | Normal Hepatic Function | Participants with normal hepatic function and matched, by average age, weight, and gender as much as practically possible with participants with moderate hepatic impairment. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 Plasma PF-07321332 | Cmax was the maximum observed plasma concentration and was directly observed from data. Concentration values below the lower limit of quantification (LLQ) were set to zero. Geometric mean analysis was on the log scale. Zero values were not included in geometric mean and geometric coefficient of variation calculation. The geometric coefficient of variation was expressed in percentage. | The PK parameter analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms per milliliter (ug/mL) | Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours |
|
From the first dose of study treatment to the last dose of study treatment date +35 days (up to 2 months)
The same event may appear as both an adverse event (AE) and an serious adverse event (SAE). An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Normal Hepatic Function | Participants with normal hepatic function and matched, by average age, weight, and gender as much as practically possible with participants with moderate hepatic impairment. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | MedDRA v24.1 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jun 25, 2021 | Oct 24, 2022 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 29, 2021 | Oct 24, 2022 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C000718217 | nirmatrelvir |
| D019438 | Ritonavir |
| ID | Term |
|---|---|
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
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| Drug |
PK Boosting agent |
|
| Up to 2 months |
| Number of Participants With Abnormal Electrocardiograms (ECGs) | ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (>=) 300 millisecond (msec), b) >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec. 2. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) >=140 msec, b) >=50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and <=480 msec, b) >480 msec and <=500 msec, c) >500 msec, d) >30 msec and <=60 msec increase from baseline, e) >60 msec increase from baseline. | Up to 2 months |
| Number of Participants With Abnormal Vital Signs | Criteria for vital signs abnormalities: increase or decrease from baseline in systolic blood pressure (SBP) >=30 mm Hg and increase or decrease from baseline in diastolic blood pressure (DBP) >=20 mm Hg; the value of SBP <90 mm Hg; the value of DBP <50 mm Hg; the value of pulse rate <40 bpm or >120 bpm. | Up to 2 months |
| Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology; clinical chemistry; urinalysis. | Up to 2 months |
| Saint Paul |
| Minnesota |
| 55114 |
| United States |
| BG001 | Moderate Hepatic Impairment | Moderate Hepatic Impairment: Participants with moderate hepatic impairment (grade B) with a Child-Pugh Score of 7-9. The CP classification assesses 5 hepatic parameters (serum total bilirubin, serum albumin, prothrombin time prolongation, ascites, and encephalopathy grade) on a scale of 1 to 3 (most severe derangement). Total moderate hepatic impairment score range is 7 to 9. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
Participants with normal hepatic function and matched, by average age, weight, and gender as much as practically possible with participants with moderate hepatic impairment. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing.
| OG001 | Moderate Hepatic Impairment | Moderate Hepatic Impairment: Participants with moderate hepatic impairment (grade B) with a Child-Pugh Score of 7-9. The CP classification assesses 5 hepatic parameters (serum total bilirubin, serum albumin, prothrombin time prolongation, ascites, and encephalopathy grade) on a scale of 1 to 3 (most severe derangement). Total moderate hepatic impairment score range is 7 to 9. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing. |
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-07321332 | AUClast was area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration. The geometric coefficient of variation was expressed in percentage. | The PK parameter analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | micrograms/milliliter/hour (ug*hr/mL) | Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours |
|
|
|
|
| Primary | Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-07321332 | AUCinf was defined as area under the plasma concentration-time curve from time zero to infinity. The geometric coefficient of variation was expressed in percentage. | The PK parameter analysis population was defined as all participants assigned to investigational product and treated who had at least 1 of the PK parameters of primary interest measured. | Posted | Geometric Mean | Geometric Coefficient of Variation | ug*hr/mL | Day 1 at 0 (pre-dose for PF-07321332), 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours, Day 2 at 24 and 36 hours, and Day 3 at 48 hours |
|
|
|
|
| Secondary | Number of Participants With an Treatment Emergent Adverse Event (TEAE) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent adverse event (TEAE) means event between first dose of study treatment and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. An SAE was an AE resulting in any of death; inpatient hospitalization; life-threatening experience; disability; congenital anomaly or deemed significant for any other reason. | Population 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 | Up to 2 months |
|
|
|
| Secondary | Number of Participants With Abnormal Electrocardiograms (ECGs) | ECG categorical summarization criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) greater than or equal to (>=) 300 millisecond (msec), b) >=25% increase when baseline is > 200 msec or >=50% increase when baseline is less than or equal to (<=) 200 msec. 2. QRS duration (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) >=140 msec, b) >=50% increase from baseline. 3. QTcF interval (QT corrected using the Fridericia formula): a) >450 msec and <=480 msec, b) >480 msec and <=500 msec, c) >500 msec, d) >30 msec and <=60 msec increase from baseline, e) >60 msec increase from baseline. | Population 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 | Up to 2 months |
|
|
|
| Secondary | Number of Participants With Abnormal Vital Signs | Criteria for vital signs abnormalities: increase or decrease from baseline in systolic blood pressure (SBP) >=30 mm Hg and increase or decrease from baseline in diastolic blood pressure (DBP) >=20 mm Hg; the value of SBP <90 mm Hg; the value of DBP <50 mm Hg; the value of pulse rate <40 bpm or >120 bpm. | Population 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 | Up to 2 months |
|
|
|
| Secondary | Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality) | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology; clinical chemistry; urinalysis. | Population 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 | Up to 2 months |
|
|
|
| 0 |
| 8 |
| 0 |
| 8 |
| 3 |
| 8 |
| EG001 | Moderate Hepatic Impairment | Moderate Hepatic Impairment: Participants with moderate hepatic impairment (grade B) with a Child-Pugh Score of 7-9. The CP classification assesses 5 hepatic parameters (serum total bilirubin, serum albumin, prothrombin time prolongation, ascites, and encephalopathy grade) on a scale of 1 to 3 (most severe derangement). Total moderate hepatic impairment score range is 7 to 9. Participants received single 100 mg dose of PF-07321332 administered orally in combination with the PK boosting agent ritonavir administered as a 100 mg dose at -12, 0, 12, and 24 hours relative to PF-07321332 dosing. | 0 | 8 | 0 | 8 | 4 | 8 |
| Injection site pruritus | General disorders | MedDRA v24.1 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA v24.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
|
| Dysgeusia | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA v24.1 | Non-systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA v24.1 | Non-systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | MedDRA v24.1 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006573 |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value ≥ 140 |
|
| QRS INTERVAL NOT OTHERWISE SPECIFIED (MSEC): %Change ≥ 50% |
|
| QT INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value > 500 |
|
| QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 |
|
| QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 |
|
| QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Value > 500 |
|
| QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): 30 < Change ≤ 60 |
|
| QTC INTERVAL NOT OTHERWISE SPECIFIED (MSEC): Change > 60 |
|
| QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): 450 < Value ≤ 480 |
|
| QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): 480 < Value ≤ 500 |
|
| QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): Value > 500 |
|
| QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): 30 < Change ≤ 60 |
|
| QTCF - FRIDERICIA'S CORRECTION FORMULA NOT OTHERWISE SPECIFIED (MSEC): Change > 60 |
|
| SBP: Change >= 30 mmHg decrease from baseline |
|
| DBP: Value <50 mmHg |
|
| DBP: Change >= 20 mmHg increase from baseline |
|
| DBP: Change >= 20 mmHg decrease from baseline |
|
| Pulse Rate: Value <40 bpm |
|
| Pulse Rate: Value >120 bpm |
|
| HEMATOLOGY: Eosinophils (10^3/mm^3) >1.2× upper limit of normal (ULN) |
|
|
| HEMATOLOGY: Monocytes (10^3/mm^3) >1.2× ULN |
|
|
| CLINICAL CHEMISTRY: Direct Bilirubin (mg/dL) >1.5× ULN |
|
|
| CLINICAL CHEMISTRY: Aspartate Aminotransferase (U/L) >3.0× ULN |
|
|
| CLINICAL CHEMISTRY: Calcium (mg/dL) >1.1× ULN |
|
|
| CLINICAL CHEMISTRY: Glucose (mg/dL) >1.5× ULN |
|
|
| URINALYSIS: URINE Hemoglobin ≥1 |
|
|
| URINALYSIS: Urobilinogen ≥1 |
|
|
| URINALYSIS: Leukocyte Esterase ≥1 |
|
|
| URINALYSIS: Urine Microscopic Exam ≥1 |
|
|