Relative Bioavailability Study of Nirmatrelvir/Ritonavir Oral Powder Relative to the Commercial Tablets and Estimation of the Effect of Food on Bioavailability of the Nirmatrelvir/Ritonavir Oral Powder in Healthy Participants.

Biological Availability Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05544786
• Other study ID #: C4671036
• Secondary ID: 2022-002497-86
• Status: Completed
• Phase: Phase 1
• Start date: September 28, 2022
• Est. completion date: November 29, 2022

Study information

• Verified date: November 2023
• 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 (rBA) of nirmatrelvir/ritonavir oral powder in 3 different food vehicles relative to the Paxlovid® tablets under fasted condition in healthy adult participants, and to estimate the effect of food on the rBA of the nirmatrelvir/ritonavir oral powder formulation. The study will also assess the safety, tolerability, and palatability of nirmatrelvir/ritonavir oral powder in healthy adult participants.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: November 29, 2022
• Est. primary completion date: November 29, 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

• Biological Availability

Intervention

Drug:
• Nirmatrelvir/ ritonavir
Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition
• Nirmatrelvir/Ritonavir
Single oral dose of nirmatrelvir/ritonavir mixed in water under fasted condition
• Nirmatrelvir/Ritonavir
Single oral dose of nirmatrelvir/ritonavir mixed in infant formula under fasted condition
• Nirmatrelvir/ritonavir
Single oral dose of nirmatrelvir/ritonavir mixed in vanilla pudding under fasted condition
• Nirmatrelvir/ritonavir
Single oral dose of nirmatrelvir/ritonavir mixed in vanilla pudding under fed condition

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit - Brussels	Brussels	Bruxelles-capitale, Région DE

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. 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; AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
Primary	AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for nirmatrelvir was calculated 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 after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
Primary	Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	Cmax was defined maximum observed concentration. Cmax for nirmatrelvir 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 after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
Primary	AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. AUCinf for ritonavir 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; AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
Primary	AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for ritonavir was calculated 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 after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
Primary	Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	Cmax was defined maximum observed concentration. Cmax for ritonavir 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 after dose on Day 1 of Periods 1, 2, 3, 4, and 5.
Secondary	AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions	AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. AUCinf for nirmatrelvir (under fasted/fed conditions) 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; AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.
Secondary	AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions	AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for nirmatrelvir (under fasted/fed conditions) was calculated 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 after dose on Day 1 of Periods 4 and 5.
Secondary	Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions	Cmax was defined maximum observed concentration. Cmax for nirmatrelvir (under fasted/fed conditions) 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 after dose on Day 1 of Periods 4 and 5.
Secondary	AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions	AUCinf was defined as area under the concentration-time curve from time 0 extrapolated to infinity. AUCinf for ritonavir (under fasted/fed conditions) 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; AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours after dose on Day 1 of Periods 4 and 5.
Secondary	AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions	AUClast was defined as area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration. AUClast for ritonavir (under fasted/fed conditions) was calculated 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 after dose on Day 1 of Periods 4 and 5.
Secondary	Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions	Cmax was defined maximum observed concentration. Cmax for ritonavir (under fasted/fed conditions) 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 after dose on Day 1 of Periods 4 and 5.
Secondary	Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a participant who received study intervention without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study intervention and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A serious AE (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; suspected transmission via a Pfizer product of an infectious agent, pathogenic or non-pathogenic. TEAEs included SAEs and all non-SAEs that occurred during the study.	Baseline up to 28 days after last dose of study intervention (ie, up to 48 days).
Secondary	Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)	The following laboratory test abnormalities (without regard to baseline abnormality) were reported during the study: monocytes/leukocytes (percentage [%]) is larger than (>) 1.2x upper limit of normal (ULN), specific gravity (scalar) >1.030, and urine hemoglobin was larger or equal to (>=) 1.	Baseline up to Day 4 of Period 5 (approximately 20 days)
Secondary	Number of Participants With Clinically Significant Vital Signs	Supine blood pressure and pulse rate were measured with the participant's arm supported at the level of the heart and recorded after approximately 5 minutes of rest. Vital signs were done predose, 2 hours and 6 hours post dose on Day 1 of each treatment period and also on Day 4 of Period 5. Clinical significance of vital signs was determined at the investigator's discretion.	Baseline up to Day 4 of Period 5 (approximately 20 days).
Secondary	Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Values	A single 12-lead ECG was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QT, and QTc intervals and QRS complex. All scheduled ECGs were performed after the participant has rested quietly for at least 5 minutes in a supine position. Clinical significance of ECG values was determined at the investigator's discretion.	Baseline up to Day 4 of Period 5 (approximately 20 days).
Secondary	Number of Participants With Clinically Significant Physical Examination (PE) Values	A complete physical examination 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.; Completed PE were performed by trained medical personnel at the investigator site at Screening or Period 1 Day 1 only. A brief PE might be performed at other designated time points at the discretion of the investigator. Clinical significance of physical examination values was determined at the investigator's discretion.	Screening, Baseline up to Day 4 of Period 5 (approximately 20 days).
Secondary	Taste Assessment of Mouth Feel After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles	The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.	1, 5, 10 and 20 minutes 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	The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.	1, 5, 10 and 20 minutes 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	The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.	1, 5, 10 and 20 minutes 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	The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.	1, 5, 10 and 20 minutes 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	The sensory attributes of nirmatrelvir/ritonavir oral powder were evaluated by the participant using a Palatability Questionnaire. Each participant complete the palatability survey immediately following dosing (within 1 min) and at 5, 10, and 20 minutes post oral administration of nirmatrelvir/ritonavir oral powder. For the taste assessment of the study, the data used in the analysis were transcribed and rescaled to a score from 0 (good) to 100 (bad) from the raw measurements on the questionnaire.	1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period.

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