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.
- Conditions
- Biological Availability
- Interventions
- Registration Number
- NCT05544786
- Lead Sponsor
- Pfizer
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment E: Nirmatrelvir/ ritonavir Nirmatrelvir/ritonavir Nirmatrelvir/ ritonavir with food and vanilla pudding Treatment A: Nirmatrelvir/ritonavir Nirmatrelvir/ ritonavir Nirmatrelvir and ritonavir tablets Treatment B: Nirmatrelvir/ ritonavir Nirmatrelvir/ritonavir Nirmatrelvir/ritonavir with water Treatment C: Nirmatrelvir/ ritonavir Nirmatrelvir/ritonavir Nirmatrelvir/ ritonavir with infant formula Treatment D: Nirmatrelvir/ ritonavir Nirmatrelvir/ritonavir Nirmatrelvir/ ritonavir with vanilla pudding
- Primary Outcome Measures
Name Time Method Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 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. Cmax was defined maximum observed concentration. Cmax for nirmatrelvir was observed directly from data.
AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 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. 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.
AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 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. 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.
AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 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. 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.
AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 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. 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.
Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 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. Cmax was defined maximum observed concentration. Cmax for ritonavir was observed directly from data.
- Secondary Outcome Measures
Name Time Method Number of Participants With Clinically Significant Vital Signs Baseline up to Day 4 of Period 5 (approximately 20 days). 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.
Taste Assessment of Bitterness After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period. 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.
Cmax of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions 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. Cmax was defined maximum observed concentration. Cmax for nirmatrelvir (under fasted/fed conditions) was observed directly from data.
AUClast of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions 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. 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.
AUClast of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions 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. 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.
AUCinf of Nirmatrelvir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions 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. 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.
Number of Participants With Clinically Significant 12-Lead Electrocardiogram (ECG) Values Baseline up to Day 4 of Period 5 (approximately 20 days). 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.
Taste Assessment of Throat Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period. 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.
AUCinf of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions 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. 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.
Cmax of Ritonavir Following the Administration of Nirmatrelvir/Ritonavir Mixed With Vanilla Pudding Under Fasted/Fed Conditions 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. Cmax was defined maximum observed concentration. Cmax for ritonavir (under fasted/fed conditions) was observed directly from data.
Number of Participants With All-Causality and Treatment-Related Treatment-emergent Adverse Events (TEAEs) Baseline up to 28 days after last dose of study intervention (ie, up to 48 days). 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.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) Baseline up to Day 4 of Period 5 (approximately 20 days) 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.
Number of Participants With Clinically Significant Physical Examination (PE) Values Screening, Baseline up to Day 4 of Period 5 (approximately 20 days). 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.Taste Assessment of Tongue/Mouth Burn After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period. 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.
Taste Assessment of Mouth Feel After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period. 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.
Taste Assessment of Overall Liking After Administration of Nirmatrelvir/Ritonavir in Different Delivery Vehicles 1, 5, 10 and 20 minutes after tasting each study intervention on Day 1 of each period. 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.
Trial Locations
- Locations (1)
Pfizer Clinical Research Unit - Brussels
🇧🇪Brussels, Bruxelles-capitale, Région DE, Belgium