Relative Bioavailability Study of 4 Different Formulations of PF-07321332 Relative to the Commercial Tablet Formulation

A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE-DOSE, CROSSOVER STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF PF-07321332 FOLLOWING ORAL ADMINISTRATION OF 4 DIFFERENT FORMULATIONS RELATIVE TO THE COMMERCIAL TABLET FORMULATION IN HEALTHY ADULT PARTICIPANTS UNDER FASTED CONDITIONS

The purpose of this study is to estimate the relative bioavailability of PF-07321332 in different formulations in healthy adult participants.

Study Overview

• Status: Completed
• Conditions: Bioavailability
• Intervention / Treatment: Drug: PF-07321332/ritonavir; Drug: PF-07321332/ritonavir; Drug: PF-07321332

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Pfizer Clinical Research Unit - New Haven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination (PE), laboratory tests, vital signs and standard 12 lead ECGs.
• Body mass index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb).
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures

Exclusion Criteria:

• Positive test result for SARS-CoV-2 infection at the time of Screening or Day -1.
• 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).
• Clinically relevant abnormalities requiring treatment (eg, acute myocardial infarction, unstable ischemic conditions, evidence of ventricular dysfunction, serious tachy or brady arrhythmias) or indicating serious underlying heart disease (eg, prolonged PR interval, cardiomyopathy, heart failure greater than New York Heart Association (NYHA) 1, underlying structural heart disease, Wolff Parkinson-White syndrome).
• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
• History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, hepatitis B surface antigen (HBsAg), or hepatitis B surface antibody (HCVAb). Hepatitis B vaccination is allowed.
• Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
• Participant who have received a COVID-19 vaccine within 7 days before screening or admission, or who are to be vaccinated with a COVID-19 vaccine at any time during the study confinement period.
• A positive urine drug test.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A: PF-0732133/ritonavir; PF-07321332 ritonavir	Drug: PF-07321332/ritonavir; PF-07321332 ritonavir will be administered as single dose orally; Drug: PF-07321332/ritonavir; PF-07321332 ritonavir will be administered as single oral dose orally.
Experimental: Treatment B: PF-07321332/ritonavir; PF-07321332 ritonavir	Drug: PF-07321332/ritonavir; PF-07321332 ritonavir will be administered as single dose orally; Drug: PF-07321332/ritonavir; PF-07321332 ritonavir will be administered as single oral dose orally.
Experimental: Treatment C: PF-07321332/ritonavir; PF-07321332 ritonavir	Drug: PF-07321332/ritonavir; PF-07321332 ritonavir will be administered as single dose orally; Drug: PF-07321332/ritonavir; PF-07321332 ritonavir will be administered as single oral dose orally.
Experimental: Treatment D: PF-07321332/ritonavir; PF-07321332 ritonavir	Drug: PF-07321332/ritonavir; PF-07321332 ritonavir will be administered as single dose orally; Drug: PF-07321332/ritonavir; PF-07321332 ritonavir will be administered as single oral dose orally.
Experimental: Treatment E: PF-07321332; PF-07321332	Drug: PF-07321332; PF-07321332 will be administered as single oral dose orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir	AUClast for nirmatrelvir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUClast for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.	0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir	AUCinf for nirmatrelvir was calculated by AUClast + (Clast/kel), where Clast was the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration time curve. Natural log-transformed AUCinf for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUCinf for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.	0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
Maximum Plasma Concentration (Cmax) of Nirmatrelvir	Cmax for nirmatrelvir was observed directly from data. Natural log-transformed Cmax for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed Cmax for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.	0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs might arise from symptoms or other complaints reported to the investigator by the participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative), or they might arise from clinical findings of the investigator or other healthcare providers (clinical signs, test results, etc.). TEAEs were those with initial onset or increasing in severity after the first dose of study treatment.	Baseline up to 35 days after last dose of study intervention (up to 12 weeks)
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	The laboratory abnormality parameters included Chemistry: bicarbonate (milliequivalents per liter [mEq/L]) <0.9 x lower limit of normal (LLN), urobilinogen (ehrlich units per deciliter [EU/dL]) >=1, and fibrinogen (milligram/deciliter [mg/dL]) >1.25 x baseline; Urinalysis: URINE hemoglobin (Scalar) >=1, only those categories in which at least 1 participant had data were reported. All the safety laboratory samples were collected following at least a 4 hour fast. Clinical laboratory evaluations only included treatments of nirmatrelvir SDD suspension/ritonavir 300/100 mg and nirmatrelvir SDD suspension 300 mg. No participant was evaluable for clinical laboratory evaluations for the other treatments.	Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose) and Day4 of Period 5 (4 days after the last dose on study discharge day). Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period
Number of Participants With Vital Signs Abnormalities	Single supine blood pressure (BP) and pulse rate (PR) were measured with the participant's arm supported at the level of the heart and recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm (preferably the dominant arm) was used throughout the study. Participants were instructed not to speak during measurements.	Screening (D28-D2), D1 of Period 1 (before 1st dose), D1 hr 0,2,and 6 of each period, and D4 of Period 5 (4 days after the last dose on study discharge day). Each treatment Period was 4 days long (D1-D4) with a minimum 4 days washout between each period
Number of Participants With ECG Abnormalities	Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) were collected. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position.	Screening (from D-28 to D-2), D1, hr0 of Period 1 (before 1st dose) and D4 of Period 5 (4 days after last dose on study discharge day). Each treatment period was 4 days long (D1 to D4) with a minimum of 4 days washout between each period
Number of Participants With Physical Examination Abnormalities	A complete PE included, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief physical examination included, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant reported symptoms.	Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose. Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2022
• Primary Completion (Actual): May 16, 2022
• Study Completion (Actual): May 16, 2022

Study Registration Dates

• First Submitted: February 25, 2022
• First Submitted That Met QC Criteria: February 25, 2022
• First Posted (Actual): March 3, 2022

Study Record Updates

• Last Update Posted (Actual): June 11, 2025
• Last Update Submitted That Met QC Criteria: May 23, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); coronavirus disease 2019 (COVID-19)
• Additional Relevant MeSH Terms: Viral Protease Inhibitors; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Protease Inhibitors; Enzyme Inhibitors; Antiviral Agents; Cytochrome P-450 Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Nirmatrelvir; Ritonavir
• Other Study ID Numbers: C4671008; NCT05263895 (Registry Identifier: ClinicalTrials.gov)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No