Study to Estimate the Effects of Hepatic Impairment on the Pharmacokinetics (PK) of PF-07321332

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05005312
• Other study ID #: C4671010
• Status: Completed
• Phase: Phase 1
• Start date: August 31, 2021
• Est. completion date: December 7, 2021

Study information

• Verified date: October 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: December 7, 2021
• Est. primary completion date: December 7, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• PF-07321332
Tablet
• Ritonavir
PK Boosting agent

Locations

Country	Name	City	State
United States	Prism Research LLC dba Nucleus Network	Saint Paul	Minnesota
United States	Orange County Research Center	Tustin	California

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	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 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
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.	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.	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.	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.	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.	Up to 2 months

External Links

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