Phase 1
N=27
Renal Impairment Study of PF-07321332 Boosted With Ritonavir in Adult Participants With Renal Impairment and in Healthy Participants With Normal Renal Function.
Renal Impairment
Bottom Line
View on ClinicalTrials.gov: NCT04909853 ↗Enrolled (actual)
27
Serious AEs
2.9%
Results posted
Aug 2023
Primary outcome: Primary: Maximum Observed Plasma Concentration (Cmax) of PF-07321332 — 1600; 2077; 2210; 2369 Nanogram per milliliter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- PF-07321332/ritonavir (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Oct 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Observed Plasma Concentration (Cmax) of PF-07321332 |
1600; 2077; 2210; 2369 | — |
| PRIMARY Area Under the Plasma Concentration-time Profile From Time Zero (0) to Extrapolated Infinite Time (AUCinf) of PF-07321332 |
14460; 17910; 27110; 44040 | — |
| PRIMARY Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48) |
31.20; 42.65; 30.83; 18.46 | — |
| PRIMARY Renal Clearance (CLr) of PF-07321332 |
2.180; 2.395; 1.154; 0.4398 | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (SAEs), Treatment Emergent Treatment Related AEs and Treatment Emergent Treatment Related SAEs |
2; 1; 1; 5; 0; 0 | — |
| SECONDARY Number of Participants With Clinical Laboratory Abnormalities |
5; 4; 8; 8 | — |
| SECONDARY Number of Participants With Clinically Significant Vital Signs Abnormalities |
0; 0; 0; 1 | — |
| SECONDARY Number of Participants With Clinically Significant Findings in Physical Examination |
0; 1; 0; 0 | — |
| SECONDARY Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities |
0; 0; 0; 1 | — |
| SECONDARY Plasma Concentration of PF-07321332 at 12 Hours Post Dose (C12) |
341.9; 438.0; 785.6; 1213 | — |
| SECONDARY Plasma Concentration of PF-07321332 at 24 Hours Post Dose (C24) |
99.10; 112.8; 179.1; 694.2 | — |
| SECONDARY Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07321332 |
2.000; 2.000; 2.500; 3.000 | — |
| SECONDARY Area Under the Plasma Concentration-time Profile From Time Zero (0) to the Time of the Last Quantifiable Concentration (AUClast) of PF-07321332 |
14270; 17770; 26660; 39420 | — |
| SECONDARY Apparent Clearance (CL/F) of PF-07321332 From Plasma |
6.913; 5.581; 3.689; 2.270 | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of PF-07321332 |
74.95; 51.95; 50.34; 42.73 | — |
| SECONDARY Terminal Elimination Plasma Half-life (t1/2) of PF-07321332 |
7.725; 6.606; 9.948; 13.37 | — |
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 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.
Data sourced from ClinicalTrials.gov (NCT04909853). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.