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

Phase 1

Completed

• Conditions: Bioavailability
• Interventions: Drug: PF-07321332/ritonavir

• Registration Number: NCT05263921
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-02-25
• Study First Submitted QC: 2022-02-25
• Study First Posted: 2022-03-03
• Study Start: 2022-03-10
• Primary Completion: 2022-05-19
• Study Completion: 2022-05-19
• Results First Submitted: 2023-05-02
• Status Verified: 2024-06
• Results First Submitted QC: 2024-06-05
• Last Update Submitted: 2024-06-05
• Results First Posted: 2024-06-06
• Last Update Posted: 2024-06-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Treatment A: PF-07321332/ritonavir	PF-07321332/ritonavir	PF-07321332 ritonavir
Treatment B: PF-07321332/ritonavir	PF-07321332/ritonavir	PF-07321332/ritonavir mixed with water
Treatment D: PF-07321332/ritonavir	PF-07321332/ritonavir	PF-07321332/ritonavir mixed with vanilla pudding
Treatment C: PF-07321332/ritonavir	PF-07321332/ritonavir	PF-07321332/ritonavir mixed with applesauce

Primary Outcome Measures

Name	Time	Method
Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	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	Maximum plasma concentration (Cmax) was measured. Cmax was observed directly from data.
AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	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	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.
AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	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	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.
Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	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	Maximum plasma concentration (Cmax) was measured. Cmax was observed directly from data.
AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	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	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.
AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles Under Fasted Conditions	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	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.

Secondary Outcome Measures

Name	Time	Method
Taste Assessment of Tongue/Mouth Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	1, 5, 10, 20 min after tasting each study intervention on Day 1 of each period.	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.
Number of Participants With Laboratory Abnormalities	Screening, Period 1 Day -1, Period 4 Day 4 and early termination/discontinuation.	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.
Number of Participants With Clinically Significant Vital Sign Values	Screening, Day 1 of each period and early termination/discontinuation.	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.
Number of Participants With Treatment-Emergent Adverse Event	Baseline up to Follow-up (35 days after last dose administration), an average of 10 weeks.	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.
Number of Participants With Clinically Significant Abnormal Electrocardiogram Values	Screening, Period 1 Day 1 and Period 4 Day 4.	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.
Number of Participants With Clinically Significant Physical Examination Values	Screening and Period 1 Day -1.	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.
Taste Assessment of Mouth Feel After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	1, 5, 10, 20 min after tasting each study intervention on Day 1 of each period.	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.
Taste Assessment of Overall Liking After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	1, 5, 10, 20 min after tasting each study intervention on Day 1 of each period.	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.
Taste Assessment of Bitterness After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	1, 5, 10, 20 min after tasting each study intervention on Day 1 of each period.	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.
Taste Assessment of Throat Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	1, 5, 10, 20 min after tasting each study intervention on Day 1 of each period.	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.

Trial Locations

Locations (1)

Pfizer Clinical Research Unit - New Haven; 🇺🇸 New Haven, Connecticut, United States