Relative Bioavailability Study of Nirmatrelvir/Ritonavir 4 Different Fixed Dose Combination Tablets Relative to the Commercial Tablets in Healthy Participants

AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time. 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 (Clast). AUClast for nirmatrelvir was calculated by Linear/Log trapezoidal method.

Cmax was defined as maximum plasma concentration. Cmax for nirmatrelvir was observed directly from data.

AUCinf was defined as area under the plasma concentration-time profile from time 0 extrapolated to infinite time. 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 (Clast). AUClast for ritonavir was calculated by Linear/Log trapezoidal method.

Cmax was defined as maximum plasma concentration. Cmax for ritonavir was observed directly from data.

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness to study treatment was assessed by the investigator. A serious adverse event (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. Treatment-emergent were events between first dose of study treatment and up to approximately 51 days that were absent before treatment or that worsened relative to pretreatment state.

Hematology included hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelet and white blood cell count, total neutrophils, eosinophils, etc. Chemistry included blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, bicarbonate, aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein, fibrinogen, etc. Urinalysis included pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, microscopy and culture. Clinical significance was judged by the investigator and those met the criteria of AE are listed here. Clinically significant laboratory abnormalities reported for at least 1 participant in the whole study are presented here. Baseline was defined as the last measurement taken prior to first dosing (Period 1 Day -1).

Vital signs (temperature, pulse rate and blood pressure) were obtained with participants following at least 5 minutes of supine rest. Clinical significance of vital signs was determined at the investigator's discretion. Baseline was defined as pre-dose measurement taken on Day 1 of each period.

A complete physical examination (PE) included, at a minimum, height, weight, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief PE included, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant-reported symptoms. Clinical significance of physical examination values was determined at the investigator's discretion.

A 12-lead ECG was obtained using an ECG machine that automatically calculated the heart rate and measured pulse rate, QT, and QTc intervals and QRS complex. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. Clinical significance of ECG values was determined at the investigator's discretion. Baseline was defined as pre-dose measurement taken on Day 1 of Period 1.