Biological Availability, Healthy Participants
Conditions
Keywords
Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Nirmatrelvir, Paxlovid
Brief summary
The purpose of this study is to estimate the relative bioavailability of nirmatrelvir/ritonavir of 4 different FDC tablet formulations relative to the commercial tablet formulation under fasted conditions in healthy adult participants.
Interventions
Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition
Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 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 treatment period | Cmax was defined as maximum plasma concentration. Cmax for ritonavir was observed directly from data. |
| AUCinf of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 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 treatment period | 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 of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 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 treatment period | 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 of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 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 treatment period | Cmax was defined as maximum plasma concentration. Cmax for nirmatrelvir was observed directly from data. |
| AUCinf of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 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 treatment period | 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 of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 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 treatment period | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | From baseline up to Day 4 of Period 4 (approximately 17 days) | 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). |
| Number of Participants With Clinically Significant Change From Baseline in Vital Signs | From baseline up to Day 4 of Period 4 (approximately 16 days) | 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. |
| Number of Participants With Clinically Significant Physical Examination Values | From baseline up to 35 days after last dose of study treatment (ie, up to 51 days) | 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. |
| Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) | From baseline up to Day 4 of Period 4 (approximately 16 days) | 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. |
| Number of Participants With All-Causality and Treatment-Related TEAEs | From the first dose of study treatment up to 35 days after last dose of study treatment (ie, up to 51 days) | 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. |
Countries
United States
Participant flow
Pre-assignment details
A total of 15 participants were randomized and assigned to receive the study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Sequence 1: Treatment A-> B-> C-> D Period 1: Treatment A: Single oral dose of nirmatrelvir/ritonavir 300 (2\*150)/100 mg commercial tablets under fasted conditions (Reference). Period 2: Treatment B: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) fixed dose combination (FDC) tablets Test formulation 1 (low disintegrant) under fasted conditions (Test 1).
Period 3: Treatment C: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 2 (high disintegrant) under fasted conditions (Test 2).
Period 4: Treatment D: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 3 (high drug loading \[HDL\]) under fasted conditions (Test 3).
Each enrolled participant participated in 4 study periods to receive 4 different treatments according to the sequence determined by randomization. On Day 1 of each period, participants received a single oral dose of treatment as per the randomization schedule and a minimum of 4 days washout was planned between each treatment. | 3 |
| Sequence 2: Treatment B-> C-> D-> E Period 1: Treatment B: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 1 (low disintegrant) under fasted conditions (Test 1).
Period 2: Treatment C: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 2 (high disintegrant) under fasted conditions (Test 2).
Period 3: Treatment D: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\* \[150/50 mg\]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3).
Period 4: Treatment E: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (3\*\[100/33.3 mg\]) FDC tablets Test formulation 4 under fasted conditions (Test 4).
Each enrolled participant participated in 4 study periods to receive 4 different treatments according to the sequence determined by randomization. On Day 1 of each period, participants received a single oral dose of treatment as per the randomization schedule and a minimum of 4 days washout was planned between each treatment. | 3 |
| Sequence 3: Treatment C-> D-> E-> A Period 1: Treatment C: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 2 (high disintegrant) under fasted conditions (Test 2).
Period 2: Treatment D: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3).
Period 3: Treatment E: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (3\*\[100/33.3 mg\]) FDC tablets Test formulation 4 under fasted conditions (Test 4).
Period 4: Treatment A: Single oral dose of nirmatrelvir/ritonavir 300 (2\*150)/100 mg commercial tablets under fasted conditions (Reference).
Each enrolled participant participated in 4 study periods to receive 4 different treatments according to the sequence determined by randomization. On Day 1 of each period, participants received a single oral dose of treatment as per the randomization schedule and a minimum of 4 days washout was planned between each treatment. | 3 |
| Sequence 4: Treatment D-> E-> A-> B Period 1: Treatment D: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3).
Period 2: Treatment E: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (3\*\[100/33.3 mg\]) FDC tablets Test formulation 4 under fasted conditions (Test 4).
Period 3: Treatment A: Single oral dose of nirmatrelvir/ritonavir 300 (2\*150)/100 mg commercial tablets under fasted conditions (Reference).
Period 4: Treatment B: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 1 (low disintegrant) under fasted conditions (Test 1).
Each enrolled participant participated in 4 study periods to receive 4 different treatments according to the sequence determined by randomization. On Day 1 of each period, participants received a single oral dose of treatment as per the randomization schedule and a minimum of 4 days washout was planned between each treatment. | 3 |
| Sequence 5: Treatment E-> A-> B-> C Period 1: Treatment E: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (3\*\[100/33.3 mg\]) FDC tablets Test formulation 4 under fasted conditions (Test 4).
Period 2: Treatment A: Single oral dose of nirmatrelvir/ritonavir 300 (2\*150)/100 mg commercial tablets under fasted conditions (Reference).
Period 3: Treatment B: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 1 (low disintegrant) under fasted conditions (Test 1).
Period 4: Treatment C: Single oral dose of nirmatrelvir/ritonavir 300/100 mg (2\*\[150/50 mg\]) FDC tablets Test formulation 2 (high disintegrant) under fasted conditions (Test 2).
Each enrolled participant participated in 4 study periods to receive 4 different treatments according to the sequence determined by randomization. On Day 1 of each period, participants received a single oral dose of treatment as per the randomization schedule and a minimum of 4 days washout was planned between each treatment. | 3 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 4 | Per sponsor due to study timelines | 0 | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Sequence 1: Treatment A-> B-> C-> D | Sequence 2: Treatment B-> C-> D-> E | Sequence 3: Treatment C-> D-> E-> A | Sequence 4: Treatment D-> E-> A-> B | Sequence 5: Treatment E-> A-> B-> C | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 30.3 Years STANDARD_DEVIATION 2.52 | 56.7 Years STANDARD_DEVIATION 4.16 | 50.0 Years STANDARD_DEVIATION 10.58 | 53.3 Years STANDARD_DEVIATION 17.1 | 51.7 Years STANDARD_DEVIATION 6.51 | 48.4 Years STANDARD_DEVIATION 12.64 |
| Age, Customized 18-44 years | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 5 Participants |
| Age, Customized 45-64 years | 0 Participants | 3 Participants | 2 Participants | 1 Participants | 3 Participants | 9 Participants |
| Age, Customized >=65 years | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 2 / 11 | 0 / 11 | 2 / 11 | 1 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 12 |
Outcome results
Primary
AUCinf of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)
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.
Time frame: 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 treatment period
Population: All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | AUCinf of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 27040 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 36 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | AUCinf of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 29350 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | AUCinf of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 30680 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 21 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | AUCinf of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 28200 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 40 |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | AUCinf of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 33660 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) Low Disintegrant90% CI: [94.54, 116.68]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) High Disintegrant90% CI: [98.08, 121.47]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) HDL90% CI: [90.79, 111.74]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 3\*(100/33.3 mg)90% CI: [99.58, 122.52]
Primary
AUCinf of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)
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.
Time frame: 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 treatment period
Population: All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | AUCinf of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3420 ng*hr/mL | Geometric Coefficient of Variation 76 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | AUCinf of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3230 ng*hr/mL | Geometric Coefficient of Variation 81 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | AUCinf of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3453 ng*hr/mL | Geometric Coefficient of Variation 54 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | AUCinf of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 2921 ng*hr/mL | Geometric Coefficient of Variation 85 |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | AUCinf of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 4130 ng*hr/mL | Geometric Coefficient of Variation 62 |
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) Low Disintegrant90% CI: [76.24, 103.53]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) High Disintegrant90% CI: [81.41, 111.11]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) HDL90% CI: [73.73, 99.7]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 3\*(100/33.3 mg)90% CI: [80.09, 108.26]
Primary
AUClast of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)
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.
Time frame: 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 treatment period
Population: All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | AUClast of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 26620 ng*hr/mL | Geometric Coefficient of Variation 37 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | AUClast of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 28890 ng*hr/mL | Geometric Coefficient of Variation 28 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | AUClast of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 30350 ng*hr/mL | Geometric Coefficient of Variation 21 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | AUClast of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 27630 ng*hr/mL | Geometric Coefficient of Variation 42 |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | AUClast of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 33060 ng*hr/mL | Geometric Coefficient of Variation 31 |
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) Low Disintegrant90% CI: [93.78, 117.24]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) High Disintegrant90% CI: [97.93, 122.89]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) HDL90% CI: [89.69, 111.8]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 3\*(100/33.3 mg)90% CI: [98.36, 122.57]
Primary
AUClast of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)
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.
Time frame: 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 treatment period
Population: All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | AUClast of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3224 ng*hr/mL | Geometric Coefficient of Variation 76 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | AUClast of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3044 ng*hr/mL | Geometric Coefficient of Variation 84 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | AUClast of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3297 ng*hr/mL | Geometric Coefficient of Variation 53 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | AUClast of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 2735 ng*hr/mL | Geometric Coefficient of Variation 87 |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | AUClast of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3821 ng*hr/mL | Geometric Coefficient of Variation 66 |
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) Low Disintegrant90% CI: [74.64, 104.78]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) High Disintegrant90% CI: [80.8, 114.06]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) HDL90% CI: [71.15, 99.43]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 3\*(100/33.3 mg)90% CI: [76.99, 107.54]
Primary
Cmax of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)
Cmax was defined as maximum plasma concentration. Cmax for nirmatrelvir was observed directly from data.
Time frame: 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 treatment period
Population: All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Cmax of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 2709 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Cmax of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3111 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 34 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Cmax of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3181 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Cmax of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3051 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 42 |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Cmax of Nirmatrelvir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 3556 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) Low Disintegrant90% CI: [94.97, 127.06]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) High Disintegrant90% CI: [98.92, 132.98]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) HDL90% CI: [94.64, 126.14]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 3\*(100/33.3 mg)90% CI: [100.48, 133.87]
Primary
Cmax of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation)
Cmax was defined as maximum plasma concentration. Cmax for ritonavir was observed directly from data.
Time frame: 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 treatment period
Population: All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Cmax of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 371.3 ng/mL | Geometric Coefficient of Variation 67 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Cmax of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 334.2 ng/mL | Geometric Coefficient of Variation 93 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Cmax of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 374.5 ng/mL | Geometric Coefficient of Variation 47 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Cmax of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 319.5 ng/mL | Geometric Coefficient of Variation 84 |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Cmax of Ritonavir Following the Administration of 4 Different Nirmatrelvir/Ritonavir FDC Tablets (Test Formulations) Compared to the Nirmatrelvir/Ritonavir 300(2*150)/100 mg Tablets (Reference Formulation) | 411.3 ng/mL | Geometric Coefficient of Variation 77 |
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) Low Disintegrant90% CI: [65.85, 103.74]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) High Disintegrant90% CI: [75.28, 119.49]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 2\*(150/50 mg) HDL90% CI: [65.18, 102.07]
Comparison: Reference: Nirmatrelvir/ritonavir 300(2\*150)/100 mg Test: Nirmatrelvir/ritonavir 3\*(100/33.3 mg)90% CI: [70.65, 110.57]
Secondary
Number of Participants With All-Causality and Treatment-Related TEAEs
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.
Time frame: From the first dose of study treatment up to 35 days after last dose of study treatment (ie, up to 51 days)
Population: All participants who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related TEAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality TEAEs | 2 Participants |
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality TEAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related TEAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality TEAEs | 2 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related TEAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality TEAEs | 1 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related TEAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality TEAEs | 2 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with all-causality SAEs | 0 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With All-Causality and Treatment-Related TEAEs | Number of participants with treatment-related TEAEs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG)
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.
Time frame: From baseline up to Day 4 of Period 4 (approximately 16 days)
Population: All participants who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) | 0 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) | 0 Participants |
Secondary
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
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.
Time frame: From baseline up to Day 4 of Period 4 (approximately 16 days)
Population: All participants who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With Clinically Significant Change From Baseline in Vital Signs | 0 Participants |
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis
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).
Time frame: From baseline up to Day 4 of Period 4 (approximately 17 days)
Population: Participants with at least one observation of the given laboratory test while on study treatment or during lag time.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Neutrophils (10^9/L) <0.8*lower limit of normal (LLN) | 0 Participants |
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Fibrinogen (mg/dL) >1.25*baseline | 2 Participants |
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Monocytes/Leukocytes (%) >1.2*upper limit of normal (ULN) | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Monocytes/Leukocytes (%) >1.2*upper limit of normal (ULN) | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Neutrophils (10^9/L) <0.8*lower limit of normal (LLN) | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Fibrinogen (mg/dL) >1.25*baseline | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Monocytes/Leukocytes (%) >1.2*upper limit of normal (ULN) | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Neutrophils (10^9/L) <0.8*lower limit of normal (LLN) | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Fibrinogen (mg/dL) >1.25*baseline | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Neutrophils (10^9/L) <0.8*lower limit of normal (LLN) | 1 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Fibrinogen (mg/dL) >1.25*baseline | 1 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Monocytes/Leukocytes (%) >1.2*upper limit of normal (ULN) | 1 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Monocytes/Leukocytes (%) >1.2*upper limit of normal (ULN) | 2 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Neutrophils (10^9/L) <0.8*lower limit of normal (LLN) | 0 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With Clinically Significant Laboratory Abnormalities in Hematology, Chemistry, and Urinalysis | Fibrinogen (mg/dL) >1.25*baseline | 0 Participants |
Secondary
Number of Participants With Clinically Significant Physical Examination Values
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.
Time frame: From baseline up to 35 days after last dose of study treatment (ie, up to 51 days)
Population: All participants who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Number of Participants With Clinically Significant Physical Examination Values | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Number of Participants With Clinically Significant Physical Examination Values | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Number of Participants With Clinically Significant Physical Examination Values | 0 Participants |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Number of Participants With Clinically Significant Physical Examination Values | 0 Participants |
| Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Number of Participants With Clinically Significant Physical Examination Values | 0 Participants |