Renal Impairment Study of PF-07321332 Boosted With Ritonavir in Adult Participants With Renal Impairment and in Healthy Participants With Normal Renal Function.

NCT04909853 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C4671011
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Renal Impairment

Keywords

SARS-CoV-2; COVID-19

Outcome Measures

Primary Outcomes (4)

• Maximum Observed Plasma Concentration (Cmax) of PF-07321332

  Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1

• Area Under the Plasma Concentration-time Profile From Time Zero (0) to Extrapolated Infinite Time (AUCinf) of PF-07321332

  AUCinf was calculated by AUClast + (Clast/kel). AUClast was the area under the plasma concentration-time profile from time 0 to the time of Clast. Clast was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.

  Part 1 and Part 2: 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 hours post-dose on Day 1

• Amount of PF-07321332 Excreted Unchanged in Urine Over 48 Hours (Ae48)

  Total amount of unchanged drug excreted in the urine over 48 hours.

  Part 1 and Part 2: 0 to 48 hours post dose on Day 1

• Renal Clearance (CLr) of PF-07321332

  Renal clearance was calculated as total amount of unchanged drug excreted in the urine over 48 hours (Ae48) divided by area under the plasma concentration-time profile from time 0 to 48 hours post dose.

  Part 1 and Part 2: 0 to 48 hours post dose on Day 1

Secondary Outcomes (12)

• 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

  Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

• Number of Participants With Clinical Laboratory Abnormalities

  Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

• Number of Participants With Clinically Significant Vital Signs Abnormalities

  Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

• Number of Participants With Clinically Significant Findings in Physical Examination

  Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

• Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Abnormalities

  Part 1 and Part 2: Day -1 up to maximum of 35 days after last dose (maximum of 38 days)

Study Arms (1)

PF-07321332

EXPERIMENTAL

PF 07321332/ritonavir

Drug: PF-07321332/ritonavir

Interventions

PF-07321332/ritonavir DRUG

PF-07321332 in combination with the PK boosting agent, ritonavir, being developed for the treatment of COVID-19

Also known as: PF-07321332

PF-07321332

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:

Sponsors & Collaborators

• Pfizer: lead

Study Sites (5)

Orange County Research Center

Tustin, California, 92780, United States

Location

Investigational Drug Services (IDS) University of Miami Hospitals and Clinics

Miami, Florida, 33136, United States

Location

University of Miami Division of Clinical Pharmacology

Miami, Florida, 33136, United States

Location

Genesis Clinical Research, LLC

Tampa, Florida, 33603, United States

Location

Prism Research LLC dba Nucleus Network

Saint Paul, Minnesota, 55114, United States

Location

Related Publications (1)

• Toussi SS, Neutel JM, Navarro J, Preston RA, Shi H, Kavetska O, LaBadie RR, Binks M, Chan PLS, Demers N, Corrigan B, Damle B. Pharmacokinetics of Oral Nirmatrelvir/Ritonavir, a Protease Inhibitor for Treatment of COVID-19, in Subjects With Renal Impairment. Clin Pharmacol Ther. 2022 Oct;112(4):892-900. doi: 10.1002/cpt.2688. Epub 2022 Jul 5.

  PMID: 35712797 DERIVED

Related Links

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

MeSH Terms

Conditions

Renal Insufficiency; COVID-19

Interventions

nirmatrelvir and ritonavir drug combination; nirmatrelvir

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2021
• First Posted: June 2, 2021
• Study Start: June 15, 2021
• Primary Completion: October 7, 2021
• Study Completion: October 7, 2021
• Last Updated: August 2, 2023
• Results First Posted: August 2, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)