A Study to Measure the Amount of Study Medicine in Blood in Adult Participants With COVID-19 and Severe Kidney Disease

A PHASE 1, OPEN-LABEL, NON-RANDOMIZED STUDY TO INVESTIGATE THE SAFETY AND PK FOLLOWING MULTIPLE ORAL DOSES OF PF-07321332 (NIRMATRELVIR)/RITONAVIR IN ADULT PARTICIPANTS WITH COVID-19 AND SEVERE RENAL IMPAIRMENT EITHER ON HEMODIALYSIS OR NOT ON HEMODIALYSIS

The purpose of this study is to learn about the side effects (safety) of the study medicine PF-07321332 (nirmatrelvir)/ritonavir for the treatment of mild to moderate COVID-19 infection in adults with severe renal impairment. The study will also look at the amounts of study drug in your blood. There will be 24 participants in this study; 12 of them will have severe renal impairment and not be on hemodialysis and 12 of them will be on hemodialysis.

All participants in this study will take PF-07321332 (nirmatrelvir)/ritonavir by mouth for 5 days. During this time, they will have to collect blood samples to measure the study drug levels in their blood. After taking the study drug for 5 days, the participants will have follow-up visits for about another 28 days for a total of about 34 days in the study. The study team will check how each participant is doing during regular visits at the study clinic.

Study Overview

• Status: Terminated
• Conditions: COVID-19
• Intervention / Treatment: Drug: PF-07321332 (nirmatrelvir)/ritonavir

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
      • Nephrology Consultants
    • Huntsville, Alabama, United States, 35801
      • Fresenius Kidney Care Huntsville
    • Huntsville, Alabama, United States, 35802
      • Fresenius Kidney Care Rocket City
    • Huntsville, Alabama, United States, 35805
      • Apogee Clinical Research, LLC
    • Huntsville, Alabama, United States, 35810
      • Fresenius Kidney Care Chase
    • Huntsville, Alabama, United States, 35816
      • Fresenius Kidney Care Endeavour
    • Huntsville, Alabama, United States, 35816
      • Fresenius Kidney Care Parkway
  • California
    • Granada Hills, California, United States, 91344
      • Amicis Research Center
    • Granada Hills, California, United States, 91344
      • Amicis Research Center - Granada Hills
    • Inglewood, California, United States, 90301
      • DaVita Inglewood Dialysis
    • Northridge, California, United States, 91324
      • Northridge Kidney Center
    • Redondo Beach, California, United States, 90277
      • Clinnova Research - Redondo Beach
    • Santa Clarita, California, United States, 91355
      • Santa Clarita Dialysis
    • Sun Valley, California, United States, 91352
      • laurel Canyon Dialysis
    • Victorville, California, United States, 92392
      • Desert Cities Diaylsis
    • Victorville, California, United States, 92395
      • Desert Cities Dialysis - Hesperia
  • Florida
    • Fort Lauderdale, Florida, United States, 33312
      • Fresenius Kidney Care Ft Lauderdale #2036
    • Lauderdale Lakes, Florida, United States, 33313
      • South Florida Research Institute
    • Lauderhill, Florida, United States, 33319
      • Fresenius Kidney Care Florida Kidney Center #1095
    • Saint Petersburg, Florida, United States, 33705
      • GCP Research, Global Clinical professionals
    • Tamarac, Florida, United States, 33321
      • Fresenius Kidney Care Tamarac-JV #6606
    • Tampa, Florida, United States, 33603
      • Genesis Clinical Research, LLC
    • Tampa, Florida, United States, 33603
      • Fresenius Kidney Care Hillsborough #100706
    • Tampa, Florida, United States, 33609
      • Fresenius Kidney Care Tampa #1130
    • Tampa, Florida, United States, 33610
      • Fresenius Kidney Care Ybor City #1863
    • Tampa, Florida, United States, 33615
      • Fresenius Kidney Care Town and Country #100474
    • Tampa, Florida, United States, 33624
      • Fresenius Kidney Care Carrollwood #1805
  • Idaho
    • Boise, Idaho, United States, 83702
      • Fresenius Kidney Care-Boise
    • Caldwell, Idaho, United States, 83605
      • Fresenius Kidney Care- Caldwell
    • Meridian, Idaho, United States, 83642
      • Fresenius Kidney Care-Meridian
    • Nampa, Idaho, United States, 83686
      • Liberty Dialysis- Nampa
    • Nampa, Idaho, United States, 83687
      • Boise Kidney & Hypertension Institute, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60625
      • Swedish Covenant Hospital
    • Evanston, Illinois, United States, 60201
      • NorthShore University HealthSystem - Evanston Hospital
    • Evanston, Illinois, United States, 60202
      • DaVita Evanston Renal Center
    • Glenview, Illinois, United States, 60026
      • DaVita Glen Dialysis
    • Glenview, Illinois, United States, 60026
      • NorthShore University HealthSystem - Glenbrook Hospital
    • Highland Park, Illinois, United States, 60035
      • NorthShore University HealthSystem - Highland Park Hospital
    • Skokie, Illinois, United States, 60076
      • NorthShore University HealthSystem - Skokie Hospital
    • Skokie, Illinois, United States, 60077
      • NorthShore Immediate Care Center - Skokie at Old Orchard Woods
    • Skokie, Illinois, United States, 60077
      • NorthShore University HealthSystem - Clinical Trials Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27101
      • Piedmont Dialysis Center
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hills Research Associates
    • Winston-Salem, North Carolina, United States, 27105
      • Northside Dialysis Center
  • Tennessee
    • Harriman, Tennessee, United States, 37748
      • Fresenius Kidney Care / Roane County #2829
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center, PLLC
    • Knoxville, Tennessee, United States, 37921
      • Fresenius Kidney Care / Fort Sanders #1597
    • Knoxville, Tennessee, United States, 37923
      • Fresenius Kidney Care / Cedar Bluff #6942
  • Texas
    • Arlington, Texas, United States, 76015
      • South Arlington Dialysis Center
    • Arlington, Texas, United States, 76015
      • Arlington Nephrology
    • Grand Prairie, Texas, United States, 75051
      • Grand Prairie Dialysis Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Covid-19 infection
• Severe kidney disease (on hemodialysis or not on hemodialysis)

Exclusion Criteria:

• Hospitalized
• Take medications that are not allowed
• Renal transplant patients
• HIV infection

This is not a complete list. Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-07321332 (nirmatrelvir)/ritonavir participants with severe renal impairment on hemodialysis; Patients with Covid-19 infection and severe renal impairment. Capsule and tablet once a day by mouth.	Drug: PF-07321332 (nirmatrelvir)/ritonavir; Patients with Covid-19 infection and severe renal impairment. Capsule and tablet once a day by mouth.; Other Names: Paxlovid
Experimental: PF-07321332 (nirmatrelvir)/ritonavir participants with severe renal impairment not on hemodialysis; Patients with Covid-19 infection and severe renal impairment. Capsule and tablet once a day by mouth.	Drug: PF-07321332 (nirmatrelvir)/ritonavir; Patients with Covid-19 infection and severe renal impairment. Capsule and tablet once a day by mouth.; Other Names: Paxlovid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs)	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose, meets one or more of the following criteria: 1. results in death. 2. is life-threatening. 3. Requires inpatient hospitalization or prolongation of existing hospitalization. 4. Results in persistent or significant disability/incapacity. 5. Is a congenital anomaly/birth defect. 6. Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic or nonpathogenic. 7. other important medical events. Any events occurring following start of treatment were considered treatment emergent.	From start of treatment on Day 1 to Day 34
Number of Participants With Permanent Discontinuation From Study or Study Intervention Due to Adverse Events and Serious Adverse Events	An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose, meets one or more of the following criteria: 1. results in death. 2. is life-threatening. 3. Requires inpatient hospitalization or prolongation of existing hospitalization. 4. Results in persistent or significant disability/incapacity. 5. Is a congenital anomaly/birth defect. 6. Is a suspected transmission via a Pfizer product of an infectious agent, pathogenic or nonpathogenic. 7. other important medical events. Any events occurring following start of treatment were considered treatment emergent.	From start of treatment on Day 1 to Day 34
Maximum Plasma Concentration (Cmax) of PF-07321332 (Nirmatrelvir)	Nirmatrelvir plasma concentration data were analyzed using nonlinear mixed effects models. Time frame was: For Cohort 1: Day 1 (anytime between 1-3 hours post-dose), Day 2 (anytime between 4-8 hours post-dose), Day 3 (anytime between 9-15 hours post-dose), Day 4 (pre-dose, anytime between 1-4 hours post-dose), Day 5 (pre-dose, anytime between 0.5-6 hours post-dose, anytime between 9-15 hours post-dose). For Cohort 2: Day 1 (anytime between 1-3 hours post-dose), Day 3 (pre-HD), Day 4 (pre-HD, pre-dose, anytime between 0.5-3 hours post-dose, anytime between 4-8 hours post-dose, anytime between 9-15 hours post-dose).	Treatment Day 1 to Day 5, see description for details
Apparent Volume of Distribution (Vz/F) of Nirmatrelvir	Vz/F was estimated at steady state.	Treatment Day 1 to Day 5
Area Under the Curve Over a Dosing Interval (AUC0-tau) of Nirmatrelvir	AUC0-tau was measured at 24 hours post-dose.	24 Hours after each dose on Treatment Day 1 to Day 5
Terminal Half-Life (T1/2) of Nirmatrelvir	T1/2 was observed directly from data.	Treatment Day 1 to Day 5
Trough Concentration (Ctrough) of Nirmatrelvir	Ctrough was measured at 24 hours post-dose (pre the next dose). It was analyzed using nonlinear mixed effect models.	24 Hours after each dose on Treatment Day 1 to Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemodialysis Clearance (CLd) of Nirmatrelvir	CLd of nirmatrelvir was calculated for Cohort 2 using non-compartmental analysis of arterial and venous port plasma concentration-time data. Only participants in Cohort 2 were on hemodialysis.	Pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose on Day 3 and Day 4
Fraction of Drug Removed During Dialysis (Fd) of Nirmatrelvir	Fd of nirmatrelvir was calculated for Cohort 2 using non-compartmental analysis of arterial and venous port plasma concentration-time data. Only participants in Cohort 2 were on hemodialysis.	Pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose on Day 3 and Day 4

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 7, 2022
• Primary Completion (Actual): July 11, 2023
• Study Completion (Actual): July 11, 2023

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: May 28, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: kidney disease; dialysis; COVID; renal failure; hemodialysis; Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2); Paxlovid; coronavirus disease 2019 (COVID-19); antiviral; renal dialysis; high risk; kidney failure; renal disease; mild to moderate COVID-19; nirmatrelvir
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Nirmatrelvir
• Other Study ID Numbers: C4671028; EPIC-SRI (Other Identifier: Alias Study Number); 2023-503870-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No