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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A: Nirmatrelvir/ritonavir | Active Comparator | Nirmatrelvir and ritonavir tablets |
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| Treatment B: Nirmatrelvir/ ritonavir | Experimental | Nirmatrelvir/ ritonavir test tablets |
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| Treatment C: Nirmatrelvir/ ritonavir | Experimental | Nirmatrelvir/ ritonavir test tablets |
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| Treatment D: Nirmatrelvir/ ritonavir | Experimental | Nirmatrelvir/ ritonavir test tablets |
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| Treatment E: Nirmatrelvir/ ritonavir | Experimental | Nirmatrelvir/ ritonavir test tablets |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nirmatrelvir/ ritonavir | Drug | Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition |
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| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 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. | 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 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. | 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 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New Haven Clinical Research Unit | New Haven | Connecticut | 06511 | United States |
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| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
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A total of 15 participants were randomized and assigned to receive the study intervention.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 18, 2022 | Sep 11, 2023 |
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| Nirmatrelvir/ritonavir | Drug | Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition |
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| Nirmatrelvir/ritonavir | Drug | Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition |
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| Nirmatrelvir/ ritonavir | Drug | Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition |
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| Nirmatrelvir/ ritonavir | Drug | Single oral dose of nirmatrelvir/ritonavir tablets under fasted condition |
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| 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 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. | 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 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. | 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 |
| From the first dose of study treatment up to 35 days after last dose of study treatment (ie, up to 51 days) |
| 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). | From baseline up to Day 4 of Period 4 (approximately 17 days) |
| 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. | From baseline up to Day 4 of Period 4 (approximately 16 days) |
| 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. | From baseline up to 35 days after last dose of study treatment (ie, up to 51 days) |
| 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. | From baseline up to Day 4 of Period 4 (approximately 16 days) |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| FG004 | 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. |
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| Period 2 |
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| Period 3 |
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| Period 4 |
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All participants who were enrolled in the study.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | 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. |
| BG005 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Age, Customized | Number | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | 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 |
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| 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. | 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | 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 |
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| 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. | All participants who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. | Posted | Count of Participants | Participants | From the first dose of study treatment up to 35 days after last dose of study treatment (ie, up to 51 days) |
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| 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). | Participants with at least one observation of the given laboratory test while on study treatment or during lag time. | Posted | Count of Participants | Participants | From baseline up to Day 4 of Period 4 (approximately 17 days) |
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| 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. | All participants who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. | Posted | Count of Participants | Participants | From baseline up to Day 4 of Period 4 (approximately 16 days) |
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| 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. | All participants who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. | Posted | Count of Participants | Participants | From baseline up to 35 days after last dose of study treatment (ie, up to 51 days) |
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| 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. | All participants who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received. | Posted | Count of Participants | Participants | From baseline up to Day 4 of Period 4 (approximately 16 days) |
|
From the first dose of study treatment up to 35 days after last dose of study treatment (ie, up to 51 days)
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Nirmatrelvir/Ritonavir 300(2*150)/100 mg | Participants received a single oral dose of nirmatrelvir/ritonavir 300 (2*150)/100 mg commercial tablets under fasted conditions (Reference) on Day 1 of each treatment period. | 0 | 11 | 0 | 11 | 2 | 11 |
| EG001 | Nirmatrelvir/Ritonavir 2*(150/50 mg) Low Disintegrant | Participants received a 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) on Day 1 of each treatment period. | 0 | 11 | 0 | 11 | 0 | 11 |
| EG002 | Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Participants received a 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) on Day 1 of each treatment period. | 0 | 11 | 0 | 11 | 2 | 11 |
| EG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. | 0 | 12 | 0 | 12 | 1 | 12 |
| EG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. | 0 | 12 | 0 | 12 | 2 | 12 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation | Gastrointestinal disorders | MedDRA v25.1 | Non-systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA v25.1 | Non-systematic Assessment |
| |
| Wound | Injury, poisoning and procedural complications | MedDRA v25.1 | Non-systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA v25.1 | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 28, 2022 | Sep 11, 2023 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D014777 | Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000719967 | nirmatrelvir and ritonavir drug combination |
Not provided
Not provided
Not provided
| 45-64 years |
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| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
Reference: Nirmatrelvir/ritonavir 300(2*150)/100 mg Test: Nirmatrelvir/ritonavir 2*(150/50 mg) High Disintegrant |
| Ratio (%) of Adjusted Geometric Means |
| 109.15 |
| 2-Sided |
| 90 |
| 98.08 |
| 121.47 |
| Other |
Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio and 90% CI are expressed as percentages. |
| Reference: Nirmatrelvir/ritonavir 300(2*150)/100 mg Test: Nirmatrelvir/ritonavir 2*(150/50 mg) HDL | Ratio of Adjusted Geometric Means | 100.72 | 2-Sided | 90 | 90.79 | 111.74 | Other | Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio and 90% CI are expressed as percentages. |
| Reference: Nirmatrelvir/ritonavir 300(2*150)/100 mg Test: Nirmatrelvir/ritonavir 3*(100/33.3 mg) | Ratio of Adjusted Geometric Means | 110.45 | 2-Sided | 90 | 99.58 | 122.52 | Other | Analysis done using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Ratio and 90% CI are expressed as percentages. |
Participants received a 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) on Day 1 of each treatment period. |
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
|
Participants received a 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) on Day 1 of each treatment period. |
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
|
| OG002 | Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Participants received a 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) on Day 1 of each treatment period. |
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
|
Participants received a 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) on Day 1 of each treatment period. |
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
|
Participants received a 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) on Day 1 of each treatment period.
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
|
Participants received a 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) on Day 1 of each treatment period. |
| OG002 | Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Participants received a 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) on Day 1 of each treatment period. |
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
Participants received a 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) on Day 1 of each treatment period. |
| OG002 | Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant | Participants received a 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) on Day 1 of each treatment period. |
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
Participants received a 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) on Day 1 of each treatment period.
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
| OG002 |
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant |
Participants received a 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) on Day 1 of each treatment period. |
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
| Nirmatrelvir/Ritonavir 2*(150/50 mg) High Disintegrant |
Participants received a 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) on Day 1 of each treatment period. |
| OG003 | Nirmatrelvir/Ritonavir 2*(150/50 mg) HDL | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (2* [150/50 mg]) FDC tablets Test formulation 3 (HDL) under fasted conditions (Test 3) on Day 1 of each treatment period. |
| OG004 | Nirmatrelvir/Ritonavir 3*(100/33.3 mg) | Participants received a single oral dose of nirmatrelvir/ritonavir 300/100 mg (3*[100/33.3 mg]) FDC tablets Test formulation 4 under fasted conditions (Test 4) on Day 1 of each treatment period. |
|
|
|
|