Renal Impairment Study of PF-07321332 Boosted With Ritonavir in Adult Participants With Renal Impairment and in Healthy Participants With Normal Renal Function.
Condition: Renal Impairment
MeSH terms: Renal Insufficiency
Intervention: PF-07321332/ritonavir
Intervention description: PF-07321332 in combination with the PK boosting agent, ritonavir, being developed for the treatment of COVID-19
Intervention MeSH terms: Ritonavir; Nirmatrelvir
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: SARS-CoV-2; COVID-19

Summary:

      This is a Phase 1, non-randomized, open-label, 2-part study to investigate the effect of
      renal impairment on the pharmacokinetics (PK), safety and tolerability of a single oral dose
      of PF-07321332 in combination with the PK boosting agent ritonavir. Participants will be
      selected and categorized into normal renal function or renal impairment groups based on their
      estimated glomerular filtration rate. Part 1: will be conducted in approximately 24
      participants (approximately 8 per group) with stable mild or moderate renal impairment and a
      control group of participants with normal renal function. Part 2 will be conducted in
      approximately 8 participants with stable severe renal impairment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, non-smoker and/or light smoker

          -  Have a diagnosis of stable renal impairment

          -  Meet the following estimated glomerular filtration rate (eGFR) criteria during the
             screening period (based on 2 Screening visits) based on the Chronic Kidney Disease
             Epidemiology Collaboration (CKD-EPI) equation:

               -  Mild renal impairment: eGFR between 60 - 89 mL/min.

               -  Moderate renal impairment: eGFR ≥30 mL/min and <60 mL/min.

               -  Severe renal impairment: eGFR <30 mL/min, but not requiring hemodialysis.

               -  Normal renal function: eGFR ≥90 mL/min

        Renal impairment participants:

          -  Any form of renal impairment except acute nephritic syndrome (participants with
             history of previous nephritic syndrome but in remission can be included).

          -  Good general health commensurate with the population with chronic kidney disease
             (renal impairment).

          -  Stable concomitant drug regimen for the management of individual participant's medical
             conditions, so long as they are considered necessary for the welfare of the study
             participants (eg, standard therapy for underlying diseases), and are not
             contraindicated with study drug, and are unlikely to interfere with the PK of study
             drug.

        Healthy participants with normal renal function:

          -  No clinically relevant abnormalities identified by a detailed medical history, full
             physical examination, including temperature, blood pressure (BP) and pulse rate
             measurement, 12 lead ECG and clinical laboratory tests.

          -  Demographically comparable to the group of participants with impaired renal function.

               -  Each participant's body weight within ±15 kg of the mean body weight of renal
                  impairment group.

               -  Each participant's age within ±10 years of the mean age of the renal impairment
                  group.

        Exclusion Criteria:

          -  Positive test result for SARS-CoV-2 infection at the time of screening or Day -1.

          -  History of HIV infection, hepatitis B, or hepatitis C; positive testing at screening
             for HIV, HBsAg, HBcAb, or HCVAb. As an exception a positive HBsAb test due to
             Hepatitis B vaccination is allowed.

          -  Renal transplant recipients.

          -  Urinary incontinence without catheterization

          -  Any condition possibly affecting drug absorption (eg, prior bariatric surgery,
             gastrectomy, cholecystectomy, appendectomy).

          -  Participants who have been vaccinated with COVID-19 vaccines within the past 2 weeks
             of dosing, or are to be vaccinated with these vaccines at any time during the study.

          -  A positive urine drug test, for illicit drugs, at Screening

          -  aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level >2 × upper
             limit of normal (ULN)

          -  Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome
             may have direct bilirubin measured and would be eligible for this study provided the
             direct bilirubin level is≤ ULN.

          -  History of sensitivity reactions to ritonavir or any of the formulation components of
             PF 07321332 or ritonavir.

          -  Female participants of childbearing potential who are unwilling or unable to use
             highly effective methods of contraception as outlined in Section 5.3.4 for the
             duration of the study and for at least 28 days after the administration of
             investigational product, pregnant female participants, female participants planning to
             become pregnant during the duration of the study until 28 days after the
             administration of investigational product, breastfeeding female participants.

        Renal impairment participants:

          -  Participants requiring hemodialysis and/or peritoneal dialysis

          -  Participants with other clinically significant disease that may affect the safety of
             the participant or that may affect the PK of PF-07321332. Participants with any
             significant hepatic, cardiac, or pulmonary disease or participants who are clinically
             nephrotic.

        Healthy participants with normal renal function:

          -  Evidence or history of clinically significant hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or
             allergic disease (including drug allergies, but excluding untreated, asymptomatic,
             seasonal allergies at the time of dosing).

          -  Screening supine BP >140 mm Hg (systolic) or >90 mm Hg (diastolic), following at least
             5 minutes of supine rest. If BP is >140 mm Hg (systolic) or >90 mm Hg (diastolic), the
             BP should be repeated 2 more times and the average of the 3 BP values should be used
             to determine the participant's eligibility.