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

Bioavailability Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05263921
• Other study ID #: C4671024
• Status: Completed
• Phase: Phase 1
• Start date: March 10, 2022
• Est. completion date: May 19, 2022

Study information

• Verified date: June 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: May 19, 2022
• Est. primary completion date: May 19, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Bioavailability

Intervention

Drug:
• PF-07321332/ritonavir
Single oral dose of PF-07321332/ritonavir under fasted conditions
• PF-07321332/ritonavir
Single oral dose of PF-07321332/ritonavir mixed with water under fasted conditions
• PF-07321332/ritonavir
Single oral dose of PF-07321332/ritonavir mixed with applesauce under fasted conditions
• PF-07321332/ritonavir
Single oral dose of PF-07321332/ritonavir mixed with vanilla pudding under fasted conditions

Locations

Country	Name	City	State
United States	Pfizer Clinical Research Unit - New Haven	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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.
Secondary	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 (ß 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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

External Links

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