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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Patients with Covid-19 infection and severe renal impairment. Capsule and tablet once a day by mouth.
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
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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 24 Hours after each dose on Treatment Day 1 to Day 5
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.
Time frame: 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.
Time frame: Pre-dose, 0.5, 1, 2, 3 and 4 hours post-dose on Day 3 and Day 4
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