Relative Bioavailability Study of PF-07321332/Ritonavir Oral Powder Relative to the Commercial Tablets in Healthy Participants

A PHASE 1, OPEN-LABEL, RANDOMIZED, SINGLE-DOSE, CROSSOVER STUDY TO ESTIMATE THE RELATIVE BIOAVAILABILITY OF PF-07321332/RITONAVIR ORAL POWDER IN 3 DIFFERENT DELIVERY VEHICLES RELATIVE TO THE COMMERCIAL PF-07321332/RITONAVIR TABLETS IN HEALTHY ADULT PARTICIPANTS UNDER FASTED CONDITIONS

The purpose of this study is to estimate the relative bioavailability of PF-07321332/ritonavir oral powder relative to the commercial tablet formulation under fasted condition in healthy adult participants. The study will also assess the effect of 3 different food vehicles on the relative bioavailability of the PF-07321332/ritonavir oral powder formulation as well as the safety, tolerability, and palatability of PF-07321332/ritonavir oral powder in healthy adult participants.

Study Overview

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

• 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

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Treatment A: PF-07321332/ritonavir; PF-07321332 ritonavir	Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with water under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with applesauce under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with vanilla pudding under fasted conditions
Experimental: Treatment B: PF-07321332/ritonavir; PF-07321332/ritonavir mixed with water	Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with water under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with applesauce under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with vanilla pudding under fasted conditions
Experimental: Treatment C: PF-07321332/ritonavir; PF-07321332/ritonavir mixed with applesauce	Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with water under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with applesauce under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with vanilla pudding under fasted conditions
Experimental: Treatment D: PF-07321332/ritonavir; PF-07321332/ritonavir mixed with vanilla pudding	Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with water under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with applesauce under fasted conditions; Drug: PF-07321332/ritonavir; Single oral dose of PF-07321332/ritonavir mixed with vanilla pudding under fasted conditions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	Area under the plasma concentration time profile from time 0 extrapolated to infinity (AUCinf) was measured. AUCinf was determined by AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 1 of each period
AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	Area under the plasma concentration time profile from time 0 to the time of the last quantifiable concentration (Clast) was measured. AUClast was determined by Linear/Log trapezoidal method.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 1 of each period
Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	Maximum plasma concentration (Cmax) was measured. Cmax was observed directly from data.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 1 of each period
AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	Area under the plasma concentration time profile from time 0 extrapolated to infinity (AUCinf) was measured. AUCinf was determined by AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 1 of each period
AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	Area under the plasma concentration time profile from time 0 to the time of the last quantifiable concentration (Clast) was measured. AUClast was determined by Linear/Log trapezoidal method.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 1 of each period
Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	Maximum plasma concentration (Cmax) was measured. Cmax was observed directly from data.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours post-dose on Day 1 of each period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Event	Adverse events (AEs): any untoward medical occurrence in a clinical investigation participant administered a product, without regard to relatedness. Treatment-emergent AEs (TEAEs): AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were any untoward medical occurrence at any dose that resulted in death; was life-threatening; required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Treatment-related TEAEs were any untoward medical occurrence attributed to study intervention. Relatedness to study intervention was determined by the investigator.	Baseline up to Follow-up (35 days after last dose administration), an average of 10 weeks.
Number of Participants With Laboratory Abnormalities	Participants analyzed in the laboratory abnormalities were with at least one observation of the given laboratory test while on study treatment or during lag time. Number of participants with laboratory abnormalities were number of participants with a laboratory abnormality meeting specified criteria while on study treatment or during lag time. Hematology, chemistry, urinalysis and other (SARS-CoV-2 RT-PCR, Urine drug screening, Pregnancy test (β hCG), eGFR [CKD-EPI], aPTT, PT-INR, Fibrinogen, At Screening only: FSH, HBsAg, HBsAb, HBcAb, HCVAb, HIV) were assessed.	Screening, Period 1 Day -1, Period 4 Day 4 and early termination/discontinuation.
Number of Participants With Clinically Significant Vital Sign Values	Participants with clinically significant vital sign values were with at least one observation of vital signs, which met pre-specified criteria while on study treatment or during lag time.	Screening, Day 1 of each period and early termination/discontinuation.
Number of Participants With Clinically Significant Physical Examination Values	Participants with clinically significant physical examination values were with at least one observation of physical examination, which met pre-specified criteria while on study treatment or during lag time.	Screening and Period 1 Day -1.
Number of Participants With Clinically Significant Abnormal Electrocardiogram Values	Participants with clinically significant electrocardiogram (ECG) values were with at least one observation of ECG, which met pre-specified criteria while on study treatment or during lag time.	Screening, Period 1 Day 1 and Period 4 Day 4.
Taste Assessment of Mouth Feel After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	Participants reviewed the taste questionnaire and instructions prior to the first taste assessment to treatments (B, C, D) on Period 1 Day 1. Each participant completed the Taste Assessment Survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of PF-07321332/ritonavir oral powder. For the taste assessment in the study, the data used in the analysis were transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.	1, 5, 10, 20 min after tasting each study intervention on Day 1 of each period.
Taste Assessment of Bitterness After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	Participants reviewed the taste questionnaire and instructions prior to the first taste assessment to treatments (B, C, D) on Period 1 Day 1. Each participant completed the Taste Assessment Survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of PF-07321332/ritonavir oral powder. For the taste assessment in the study, the data used in the analysis were transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.	1, 5, 10, 20 min after tasting each study intervention on Day 1 of each period.
Taste Assessment of Tongue/Mouth Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	Participants reviewed the taste questionnaire and instructions prior to the first taste assessment to treatments (B, C, D) on Period 1 Day 1. Each participant completed the Taste Assessment Survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of PF-07321332/ritonavir oral powder. For the taste assessment in the study, the data used in the analysis were transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.	1, 5, 10, 20 min after tasting each study intervention on Day 1 of each period.
Taste Assessment of Throat Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	Participants reviewed the taste questionnaire and instructions prior to the first taste assessment to treatments (B, C, D) on Period 1 Day 1. Each participant completed the Taste Assessment Survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of PF-07321332/ritonavir oral powder. For the taste assessment in the study, the data used in the analysis were transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.	1, 5, 10, 20 min after tasting each study intervention on Day 1 of each period.
Taste Assessment of Overall Liking After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	Participants reviewed the taste questionnaire and instructions prior to the first taste assessment to treatments (B, C, D) on Period 1 Day 1. Each participant completed the Taste Assessment Survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of PF-07321332/ritonavir oral powder. For the taste assessment in the study, the data used in the analysis were transcribed and rescaled to a score from 0 to 100 from the raw measurements on the Taste Assessment Questionnaire. The score of 0 was considered Favorable and the score of 100 was considered Not Favorable. Higher score means more unfavorable.	1, 5, 10, 20 min after tasting each study intervention on Day 1 of 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 10, 2022
• Primary Completion (Actual): May 19, 2022
• Study Completion (Actual): May 19, 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 6, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Nirmatrelvir; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); coronavirus disease 2019 (COVID-19)
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Nirmatrelvir
• Other Study ID Numbers: C4671024

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