Back to resultsStudy to Estimate the Effects of Hepatic Impairment on the Pharmacokinetics (PK) of PF-07321332
Primary Purpose
Hepatic Impairment
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PF-07321332
Ritonavir
Sponsored by
About this trial
This is an interventional basic science trial for Hepatic Impairment focused on measuring COVID-19, SARS-CoV-2
Eligibility Criteria
Inclusion Criteria:
- Male and female participants who are classically healthy having no clinically relevant abnormalities. No known or suspected hepatic impairment
- Stable hepatic impairment that meets the criteria for Class B of the Child-Pugh Classification
Exclusion Criteria:
- Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection).
- Participants who have been vaccinated with COVID-19 vaccines within the past week of dosing
- A positive urine drug test, for illicit drugs, at Screening
- History of sensitivity reactions to ritonavir or any of the formulation components of PF-07321332 or ritonavir.
- eGFR <60 mL/min/1.73m2 based on the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥ upper limit of normal (ULN) (for healthy participants); AST or ALT > 5x ULN (for hepatic impairment participants)
- Albumin > ULN (for healthy participants);
- Prothrombin time > ULN (for healthy participants);
- Total bilirubin level ≥1.5 × ULN [NOTE: Participants with a history of Gilbert syndrome (and hence elevated total bilirubin) are eligible provided direct bilirubin level is ≤ ULN).
Sites / Locations
- Orange County Research Center
- Prism Research LLC dba Nucleus Network
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
Healthy Volunteer
Hepatic Impairment
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05005312
Brief Title
Study to Estimate the Effects of Hepatic Impairment on the Pharmacokinetics (PK) of PF-07321332
Official Title
A PHASE 1, NON-RANDOMIZED, OPEN-LABEL STUDY TO ASSESS THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF-07321332 BOOSTED WITH RITONAVIR IN ADULT PARTICIPANTS WITH MODERATE HEPATIC IMPAIRMENT AND HEALTHY PARTICIPANTS WITH NORMAL HEPATIC FUNCTION
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
August 31, 2021 (Actual)
Primary Completion Date
December 7, 2021 (Actual)
Study Completion Date
December 7, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
COVID-19, SARS-CoV-2
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
17 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Healthy Volunteer
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Hepatic Impairment
Intervention Type
Drug
Intervention Name(s)
PF-07321332
Intervention Description
Tablet
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
PK Boosting agent
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax) of Plasma PF-07321332
Description
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.
Time Frame
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
Title
Area Under the Plasma Concentration-Time Profile From Time Zero to Time of the Last Quantifiable Concentration (AUClast) of Plasma PF-07321332
Description
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.
Time Frame
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
Title
Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Plasma PF-07321332
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Number of Participants With an Treatment Emergent Adverse Event (TEAE)
Description
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.
Time Frame
Up to 2 months
Title
Number of Participants With Abnormal Electrocardiograms (ECGs)
Description
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.
Time Frame
Up to 2 months
Title
Number of Participants With Abnormal Vital Signs
Description
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.
Time Frame
Up to 2 months
Title
Number of Participants With Abnormal Laboratory Assessments (Without Regard to Baseline Abnormality)
Description
Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology; clinical chemistry; urinalysis.
Time Frame
Up to 2 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male and female participants who are classically healthy having no clinically relevant abnormalities. No known or suspected hepatic impairment
Stable hepatic impairment that meets the criteria for Class B of the Child-Pugh Classification
Exclusion Criteria:
Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection).
Participants who have been vaccinated with COVID-19 vaccines within the past week of dosing
A positive urine drug test, for illicit drugs, at Screening
History of sensitivity reactions to ritonavir or any of the formulation components of PF-07321332 or ritonavir.
eGFR <60 mL/min/1.73m2 based on the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≥ upper limit of normal (ULN) (for healthy participants); AST or ALT > 5x ULN (for hepatic impairment participants)
Albumin > ULN (for healthy participants);
Prothrombin time > ULN (for healthy participants);
Total bilirubin level ≥1.5 × ULN [NOTE: Participants with a history of Gilbert syndrome (and hence elevated total bilirubin) are eligible provided direct bilirubin level is ≤ ULN).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Orange County Research Center
City
Tustin
State/Province
California
ZIP/Postal Code
92780
Country
United States
Facility Name
Prism Research LLC dba Nucleus Network
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Links:
URL
https://pmiform.com/clinical-trial-info-request?StudyID=C4671010
Description
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Learn more about this trial
Study to Estimate the Effects of Hepatic Impairment on the Pharmacokinetics (PK) of PF-07321332
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