Bioavailability
Conditions
Keywords
coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Brief summary
The purpose of this study is to estimate the relative bioavailability of PF-07321332 in different formulations in healthy adult participants.
Interventions
PF-07321332 ritonavir will be administered as single dose orally
DRUGPF-07321332
PF-07321332 will be administered as single oral dose orally.
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 |
|---|---|---|
| Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose | AUClast for nirmatrelvir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUClast for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect. |
| Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose | 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. Natural log-transformed AUCinf for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUCinf for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect. |
| Maximum Plasma Concentration (Cmax) of Nirmatrelvir | 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose | Cmax for nirmatrelvir was observed directly from data. Natural log-transformed Cmax for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed Cmax for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With ECG Abnormalities | Screening (from D-28 to D-2), D1, hr0 of Period 1 (before 1st dose) and D4 of Period 5 (4 days after last dose on study discharge day). Each treatment period was 4 days long (D1 to D4) with a minimum of 4 days washout between each period | Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) were collected. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Baseline up to 35 days after last dose of study intervention (up to 12 weeks) | An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs might arise from symptoms or other complaints reported to the investigator by the participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative), or they might arise from clinical findings of the investigator or other healthcare providers (clinical signs, test results, etc.). TEAEs were those with initial onset or increasing in severity after the first dose of study treatment. |
| Number of Participants With Physical Examination Abnormalities | Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose. Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period | A complete PE included, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief physical examination included, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant reported symptoms. |
| Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose) and Day4 of Period 5 (4 days after the last dose on study discharge day). Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period | The laboratory abnormality parameters included Chemistry: bicarbonate (milliequivalents per liter \[mEq/L\]) \<0.9 x lower limit of normal (LLN), urobilinogen (ehrlich units per deciliter \[EU/dL\]) \>=1, and fibrinogen (milligram/deciliter \[mg/dL\]) \>1.25 x baseline; Urinalysis: URINE hemoglobin (Scalar) \>=1, only those categories in which at least 1 participant had data were reported. All the safety laboratory samples were collected following at least a 4 hour fast. Clinical laboratory evaluations only included treatments of nirmatrelvir SDD suspension/ritonavir 300/100 mg and nirmatrelvir SDD suspension 300 mg. No participant was evaluable for clinical laboratory evaluations for the other treatments. |
| Number of Participants With Vital Signs Abnormalities | Screening (D28-D2), D1 of Period 1 (before 1st dose), D1 hr 0,2,and 6 of each period, and D4 of Period 5 (4 days after the last dose on study discharge day). Each treatment Period was 4 days long (D1-D4) with a minimum 4 days washout between each period | Single supine blood pressure (BP) and pulse rate (PR) were measured with the participant's arm supported at the level of the heart and recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm (preferably the dominant arm) was used throughout the study. Participants were instructed not to speak during measurements. |
Countries
United States
Participant flow
Pre-assignment details
Twelve participants were enrolled to 1 of 6 sequences. Each participant participated in 5 study periods to receive 5 treatments: Treatment A: nirmatrelvir (commercial tablets)/ritonavir 300/100 mg; Treatment B: nirmatrelvir (slower dissolution tablets)/ritonavir 300/100 mg; Treatment C: nirmatrelvir (large particle size tablets)/ritonavir 300/100 mg; Treatment D: nirmatrelvir (spray dried dispersion \[SDD\] suspension)/ritonavir 300/100 mg; Treatment E: nirmatrelvir 300 mg (SDD suspension)
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants enrolled in this study, Enrolled meant a participant's agreement to participate in a clinical study following completion of the informed consent process and screening. Potential participants who were screened for the purpose of determining eligibility for the study, but did not participate in the study, were not considered enrolled, unless otherwise specified by the protocol. A participant was considered enrolled if the informed consent was not withdrawn prior to participating in any study activity after screening. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 48.0 Years |
| Age, Customized 18-44 years | 5 Participants |
| Age, Customized <18 years | 0 Participants |
| Age, Customized 45-64 years | 7 Participants |
| Age, Customized >=65 years | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants |
| Race/Ethnicity, Customized Black or African American, White | 1 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 11 Participants |
| Race/Ethnicity, Customized White | 6 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 10 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 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 4 / 12 | 1 / 12 | 3 / 12 | 0 / 12 | 1 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir
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. Natural log-transformed AUCinf for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUCinf for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
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 (Commercial Tablets)/Ritonavir 300/100 mg | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir | 35540 ng*hr/mL | Geometric Coefficient of Variation 14 |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir | 32430 ng*hr/mL | Geometric Coefficient of Variation 26 |
| Nirmatrelvir (Large Particle Size Tablets)/Ritonavir 300/100 mg | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir | 36420 ng*hr/mL | Geometric Coefficient of Variation 25 |
| Nirmatrelvir (SDD Suspension)/Ritonavir 300/100 mg | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir | 48680 ng*hr/mL | Geometric Coefficient of Variation 15 |
| Nirmatrelvir (SDD Suspension) 300 mg | Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) of Nirmatrelvir | 10580 ng*hr/mL | Geometric Coefficient of Variation 50 |
Comparison: Test: Nirmatrelvir (slower dissolution tablets)/ritonavir 300/100 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [80.46, 103.51]
Comparison: Test: Nirmatrelvir (large particle size tablets)/ritonavir 300/100 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [90.36, 116.26]
Comparison: Test: Nirmatrelvir (SDD suspension)/ritonavir 300/100 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [117.09, 160.27]
Comparison: Test: Nirmatrelvir (SDD suspension) 300 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [25.45, 34.83]
Primary
Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir
AUClast for nirmatrelvir was calculated by Linear/Log trapezoidal method. Natural log-transformed AUClast for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed AUClast for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
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 (Commercial Tablets)/Ritonavir 300/100 mg | Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir | 35020 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 15 |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir | 31700 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
| Nirmatrelvir (Large Particle Size Tablets)/Ritonavir 300/100 mg | Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir | 35990 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
| Nirmatrelvir (SDD Suspension)/Ritonavir 300/100 mg | Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir | 48380 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 15 |
| Nirmatrelvir (SDD Suspension) 300 mg | Area Under the Plasma Concentration-Time Profile From Time 0 to the Time of the Last Quantifiable Concentration (Clast) (AUClast) of Nirmatrelvir | 10530 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 50 |
Comparison: Test: Nirmatrelvir (slower dissolution tablets)/ritonavir 300/100 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [79.85, 102.65]
Comparison: Test: Nirmatrelvir (large particle size tablets)/ritonavir 300/100 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [90.65, 116.53]
Comparison: Test: Nirmatrelvir (SDD suspension)/ritonavir 300/100 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [118.03, 161.69]
Comparison: Test: Nirmatrelvir (SDD suspension) 300 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [25.7, 35.2]
Primary
Maximum Plasma Concentration (Cmax) of Nirmatrelvir
Cmax for nirmatrelvir was observed directly from data. Natural log-transformed Cmax for nirmatrelvir (slower dissolution tablets and large particle size tablets) was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. Natural log-transformed Cmax for Nirmatrelvir (SDD suspension) was analyzed using a mixed effect model with sequence and treatment as fixed effects and participant within sequence as a random effect.
Time frame: 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 48 and 72 hours postdose
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 (Commercial Tablets)/Ritonavir 300/100 mg | Maximum Plasma Concentration (Cmax) of Nirmatrelvir | 3347 ng/mL | Geometric Coefficient of Variation 16 |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Maximum Plasma Concentration (Cmax) of Nirmatrelvir | 3155 ng/mL | Geometric Coefficient of Variation 23 |
| Nirmatrelvir (Large Particle Size Tablets)/Ritonavir 300/100 mg | Maximum Plasma Concentration (Cmax) of Nirmatrelvir | 3635 ng/mL | Geometric Coefficient of Variation 27 |
| Nirmatrelvir (SDD Suspension)/Ritonavir 300/100 mg | Maximum Plasma Concentration (Cmax) of Nirmatrelvir | 8840 ng/mL | Geometric Coefficient of Variation 14 |
| Nirmatrelvir (SDD Suspension) 300 mg | Maximum Plasma Concentration (Cmax) of Nirmatrelvir | 4871 ng/mL | Geometric Coefficient of Variation 30 |
Comparison: Test: Nirmatrelvir (slower dissolution tablets)/ritonavir 300/100 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [80.77, 110.05]
Comparison: Test: Nirmatrelvir (large particle size tablets)/ritonavir 300/100 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [93.04, 126.76]
Comparison: Test: Nirmatrelvir (SDD suspension)/ritonavir 300/100 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [232.32, 300.27]
Comparison: Test: Nirmatrelvir (SDD suspension) 300 mg Reference: Nirmatrelvir (commercial tablets)/ritonavir 300/100 mg90% CI: [128.01, 165.45]
Secondary
Number of Participants With ECG Abnormalities
Standard 12-lead ECGs utilizing limb leads (with a 10 second rhythm strip) were collected. All scheduled ECGs were performed after the participant had rested quietly for at least 5 minutes in a supine position.
Time frame: Screening (from D-28 to D-2), D1, hr0 of Period 1 (before 1st dose) and D4 of Period 5 (4 days after last dose on study discharge day). Each treatment period was 4 days long (D1 to D4) with a minimum of 4 days washout between each period
Population: All participants who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirmatrelvir (Commercial Tablets)/Ritonavir 300/100 mg | Number of Participants With ECG Abnormalities | 0 Participants |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Number of Participants With ECG Abnormalities | 0 Participants |
| Nirmatrelvir (Large Particle Size Tablets)/Ritonavir 300/100 mg | Number of Participants With ECG Abnormalities | 0 Participants |
| Nirmatrelvir (SDD Suspension)/Ritonavir 300/100 mg | Number of Participants With ECG Abnormalities | 0 Participants |
| Nirmatrelvir (SDD Suspension) 300 mg | Number of Participants With ECG Abnormalities | 0 Participants |
Secondary
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
The laboratory abnormality parameters included Chemistry: bicarbonate (milliequivalents per liter \[mEq/L\]) \<0.9 x lower limit of normal (LLN), urobilinogen (ehrlich units per deciliter \[EU/dL\]) \>=1, and fibrinogen (milligram/deciliter \[mg/dL\]) \>1.25 x baseline; Urinalysis: URINE hemoglobin (Scalar) \>=1, only those categories in which at least 1 participant had data were reported. All the safety laboratory samples were collected following at least a 4 hour fast. Clinical laboratory evaluations only included treatments of nirmatrelvir SDD suspension/ritonavir 300/100 mg and nirmatrelvir SDD suspension 300 mg. No participant was evaluable for clinical laboratory evaluations for the other treatments.
Time frame: Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose) and Day4 of Period 5 (4 days after the last dose on study discharge day). Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period
Population: Participants with at least 1 observation of the given laboratory test while on study treatment or during lag time.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirmatrelvir (Commercial Tablets)/Ritonavir 300/100 mg | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bicarbonate (mEq/L) <0.9 x LLN | 1 Participants |
| Nirmatrelvir (Commercial Tablets)/Ritonavir 300/100 mg | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen (EU/dL) >=1 | 1 Participants |
| Nirmatrelvir (Commercial Tablets)/Ritonavir 300/100 mg | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Fibrinogen (mg/dL) >1.25 x Baseline | 0 Participants |
| Nirmatrelvir (Commercial Tablets)/Ritonavir 300/100 mg | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin (Scalar) >=1 | 1 Participants |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | URINE Hemoglobin (Scalar) >=1 | 0 Participants |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Bicarbonate (mEq/L) <0.9 x LLN | 0 Participants |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Fibrinogen (mg/dL) >1.25 x Baseline | 1 Participants |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality) | Urobilinogen (EU/dL) >=1 | 0 Participants |
Secondary
Number of Participants With Physical Examination Abnormalities
A complete PE included, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A brief physical examination included, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant reported symptoms.
Time frame: Screening (from Day-28 to Day-2), Day-1 of Period 1 (before 1st dose. Each treatment period was 4 days long (Day1 to Day4) with a minimum of 4 days washout between each period
Population: All participants who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirmatrelvir (Commercial Tablets)/Ritonavir 300/100 mg | Number of Participants With Physical Examination Abnormalities | 0 Participants |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Number of Participants With Physical Examination Abnormalities | 0 Participants |
| Nirmatrelvir (Large Particle Size Tablets)/Ritonavir 300/100 mg | Number of Participants With Physical Examination Abnormalities | 0 Participants |
| Nirmatrelvir (SDD Suspension)/Ritonavir 300/100 mg | Number of Participants With Physical Examination Abnormalities | 0 Participants |
| Nirmatrelvir (SDD Suspension) 300 mg | Number of Participants With Physical Examination Abnormalities | 0 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. AEs might arise from symptoms or other complaints reported to the investigator by the participant (or, when appropriate, by a caregiver, surrogate, or the participant's legally authorized representative), or they might arise from clinical findings of the investigator or other healthcare providers (clinical signs, test results, etc.). TEAEs were those with initial onset or increasing in severity after the first dose of study treatment.
Time frame: Baseline up to 35 days after last dose of study intervention (up to 12 weeks)
Population: All participants who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirmatrelvir (Commercial Tablets)/Ritonavir 300/100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-Causality AEs | 4 Participants |
| Nirmatrelvir (Commercial Tablets)/Ritonavir 300/100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-Related AEs | 4 Participants |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-Causality AEs | 1 Participants |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-Related AEs | 1 Participants |
| Nirmatrelvir (Large Particle Size Tablets)/Ritonavir 300/100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-Causality AEs | 3 Participants |
| Nirmatrelvir (Large Particle Size Tablets)/Ritonavir 300/100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-Related AEs | 1 Participants |
| Nirmatrelvir (SDD Suspension)/Ritonavir 300/100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-Related AEs | 0 Participants |
| Nirmatrelvir (SDD Suspension)/Ritonavir 300/100 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-Causality AEs | 0 Participants |
| Nirmatrelvir (SDD Suspension) 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-Causality AEs | 1 Participants |
| Nirmatrelvir (SDD Suspension) 300 mg | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Treatment-Related AEs | 1 Participants |
Secondary
Number of Participants With Vital Signs Abnormalities
Single supine blood pressure (BP) and pulse rate (PR) were measured with the participant's arm supported at the level of the heart and recorded to the nearest mm Hg after approximately 5 minutes of rest. The same arm (preferably the dominant arm) was used throughout the study. Participants were instructed not to speak during measurements.
Time frame: Screening (D28-D2), D1 of Period 1 (before 1st dose), D1 hr 0,2,and 6 of each period, and D4 of Period 5 (4 days after the last dose on study discharge day). Each treatment Period was 4 days long (D1-D4) with a minimum 4 days washout between each period
Population: All participants who took at least 1 dose of study intervention. Participants were analyzed according to the product they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nirmatrelvir (Commercial Tablets)/Ritonavir 300/100 mg | Number of Participants With Vital Signs Abnormalities | 0 Participants |
| Nirmatrelvir (Slower Dissolution Tablets)/Ritonavir 300/100 mg | Number of Participants With Vital Signs Abnormalities | 0 Participants |
| Nirmatrelvir (Large Particle Size Tablets)/Ritonavir 300/100 mg | Number of Participants With Vital Signs Abnormalities | 0 Participants |
| Nirmatrelvir (SDD Suspension)/Ritonavir 300/100 mg | Number of Participants With Vital Signs Abnormalities | 0 Participants |
| Nirmatrelvir (SDD Suspension) 300 mg | Number of Participants With Vital Signs Abnormalities | 0 Participants |