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

Phase 1
Terminated
Conditions
COVID-19
Interventions
Drug: PF-07321332 (nirmatrelvir)/ritonavir
Registration Number
NCT05487040
Lead Sponsor
Pfizer
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
15
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PF-07321332 (nirmatrelvir)/ritonavir participants with severe renal impairment on hemodialysisPF-07321332 (nirmatrelvir)/ritonavirPatients with Covid-19 infection and severe renal impairment. Capsule and tablet once a day by mouth.
PF-07321332 (nirmatrelvir)/ritonavir participants with severe renal impairment not on hemodialysisPF-07321332 (nirmatrelvir)/ritonavirPatients with Covid-19 infection and severe renal impairment. Capsule and tablet once a day by mouth.
Primary Outcome Measures
NameTimeMethod
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs (SAEs)From start of treatment on Day 1 to Day 34

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.

Number of Participants With Permanent Discontinuation From Study or Study Intervention Due to Adverse Events and Serious Adverse EventsFrom start of treatment on Day 1 to Day 34

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.

Maximum Plasma Concentration (Cmax) of PF-07321332 (Nirmatrelvir)Treatment Day 1 to Day 5, see description for details

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).

Apparent Volume of Distribution (Vz/F) of NirmatrelvirTreatment Day 1 to Day 5

Vz/F was estimated at steady state.

Terminal Half-Life (T1/2) of NirmatrelvirTreatment Day 1 to Day 5

T1/2 was observed directly from data.

Trough Concentration (Ctrough) of Nirmatrelvir24 Hours after each dose on Treatment Day 1 to Day 5

Ctrough was measured at 24 hours post-dose (pre the next dose). It was analyzed using nonlinear mixed effect models.

Area Under the Curve Over a Dosing Interval (AUC0-tau) of Nirmatrelvir24 Hours after each dose on Treatment Day 1 to Day 5

AUC0-tau was measured at 24 hours post-dose.

Secondary Outcome Measures
NameTimeMethod
Hemodialysis Clearance (CLd) of NirmatrelvirPre-dose, 0.5, 1, 2, 3 and 4 hours post-dose on Day 3 and Day 4

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.

Fraction of Drug Removed During Dialysis (Fd) of NirmatrelvirPre-dose, 0.5, 1, 2, 3 and 4 hours post-dose on Day 3 and Day 4

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.

Trial Locations

Locations (52)

Fresenius Kidney Care Huntsville

🇺🇸

Huntsville, Alabama, United States

Fresenius Kidney Care Rocket City

🇺🇸

Huntsville, Alabama, United States

Apogee Clinical Research, LLC

🇺🇸

Huntsville, Alabama, United States

Nephrology Consultants

🇺🇸

Huntsville, Alabama, United States

Fresenius Kidney Care Chase

🇺🇸

Huntsville, Alabama, United States

Fresenius Kidney Care Endeavour

🇺🇸

Huntsville, Alabama, United States

Fresenius Kidney Care Parkway

🇺🇸

Huntsville, Alabama, United States

Amicis Research Center - Granada Hills

🇺🇸

Granada Hills, California, United States

Amicis Research Center

🇺🇸

Granada Hills, California, United States

DaVita Inglewood Dialysis

🇺🇸

Inglewood, California, United States

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Fresenius Kidney Care Huntsville
🇺🇸Huntsville, Alabama, United States

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