COVID-19
Conditions
Keywords
SARS-CoV-2 Infection
Brief summary
The primary hypothesis to be tested is whether or not there is a difference in time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28 between PF-07321332/ritonavir and placebo.
Detailed description
Throughout the study period, provision will be made to allow study visits to be conducted at a participant's home or at another non-clinic location, if available. The total study duration is up to 24 weeks.
Interventions
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Eligible participants with a confirmed diagnosis of SARS-CoV-2 infection will be randomized (1:1) to receive PF-07321332/ritonavir or placebo orally every 12 hours for 5 days (10 doses total).
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed SARS-CoV-2 infection 5 days prior to randomization * Initial onset of COVID-19 signs/symptoms within 5 days of randomization * Fertile participants must agree to use a highly effective method of contraception
Exclusion criteria
* Has at least one underlying medical condition associated with an increased risk of developing severe illness from COVID-19 * History of or need for hospitalization for the medical treatment of COVID-19 * Prior diagnosis of SARS-CoV-2 infection (reinfection) * Known medical history of liver disease * Receiving dialysis or have known renal impairment * Known Human Immunodeficiency Virus (HIV) infection with viral load \> 400 copies/ml or taking prohibited medications for HIV treatment * Suspected or confirmed concurrent active systemic infection other than COVID-19 * Current or expected use of any medications or substances that are highly dependent on Cytochrome P450 3A4 (CYP3A4) for clearance or are strong inducers of CYP3A4 * Has received or is expected to receive monoclonal antibody treatment or convalescent COVID-19 plasma * Has received any SARS-CoV-2 vaccine within 12 months of screening * Participating in another interventional clinical study with an investigational compound or device, including those for COVID-19 * Known prior participation in this trial or other trial involving PF-07321332 * Oxygen saturation of \< 92% on room air * Females who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sustained Alleviation of Overall COVID-19 Signs and Symptoms Through Day 28 | From Day 1 to Day 28 | Sustained alleviation of targeted COVID-19 signs/symptoms was defined as the event occurring on the first 4 consecutive days when all symptoms scored as moderate or severe at the time of enrollment were scored as mild or absent and those scored mild or absent at the time of enrollment were scored as absent. Missing severity at baseline was considered as mild. Time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28, was calculated as time (days) from start of study intervention or placebo (Day 1) until sustained alleviation of all targeted COVID-19 associated signs and symptoms. In this outcome measure time to sustained alleviation is reported consolidated for overall COVID-19 signs and symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Death Through Week 24 | From Day 1 to Week 24 | Percentage of participants with death (all-cause) event were reported in this outcome measure. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | From start of study intervention (Day 1) up to Day 34 | An AE was defined as 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. An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening ; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity ; congenital anomaly/birth defect; or that was considered as an important medical event. TEAEs were defined as events that started on or after the study medication start date and time. AEs included both serious and all non-serious adverse events. AEs that led to study discontinuation and AEs that led to discontinuation of study intervention and then continued study were also reported in this outcome measure. |
| Number of COVID-19 Related Medical Visits Per Day Through Day 28 | From Day 1 to Day 28 | Number of COVID-19 related medical visits per day were reported in this outcome measure. |
| Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28 | From Day 1 to Day 28 | — |
| Percentage of Participants With Severe Signs and Symptoms of COVID-19 Through Day 28 | From Day 1 to Day 28 | Participants recorded a daily severity rating of their symptom severity over the past 24 hours based on a 4-point scale in which 0 was reported if no symptoms were present; 1 if mild; 2 if moderate; and 3 if severe. A participant with severe score for any targeted symptoms post-baseline was counted as severe. Vomiting and diarrhea each was rated on a 4-point frequency scale where 0 was reported for no occurrence, 1 for 1 to 2 times, 2 for 3 to 4 times, and 3 for 5 or greater. Sense of smell and sense of taste each be rated on a 3-point Likert scale where 0 was reported if the sense of smell/taste was the same as usual, 1 if the sense of smell/taste was less than usual, and 2 for no sense of smell/taste. |
| Time to Sustained Resolution of Overall COVID-19 Signs and Symptoms Through Day 28 | From Day 1 to Day 28 | Sustained resolution was defined as when targeted symptoms are scored as absent for 4 consecutive days. The first day of the 4 consecutive-day period was considered the first event date. |
| Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28 | From Day 1 to Day 28 | Percentage of participants with COVID-19 related hospitalization or death from any cause during the first 28 days of the study was estimated using the Kaplan-Meier (KM) method. |
| Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | From Day 1 to Day 28 | Sustained resolution was defined as when targeted symptoms are scored as absent for 4 consecutive days. The first day of the 4 consecutive-day period was considered the first event date. In this outcome measure time to sustained resolution is reported consolidated for each COVID-19 signs and symptoms. |
| Percentage of Participants With Progression to Worsening Status of COVID-19 Signs and Symptoms | From Day 1 to Day 28 | Participants recorded a daily severity rating of their symptom severity over the past 24 hours based on a 4-point scale in which 0 was reported if no symptoms were present; 1 if mild; 2 if moderate; and 3 if severe. Vomiting and diarrhea was rated on a 4-point frequency scale where 0 is reported for no occurrence, 1 (mild) for 1 to 2 times, 2 (moderate) for 3 to 4 times, and 3 (severe) for 5 or greater. Progression to a worsening status for any targeted symptom was based up on increasing severity (i.e. the first time any targeted symptoms worsened after treatment relative to baseline). |
| Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5 | Day 1 and Day 5 | Percentage of participants with a resting peripheral oxygen saturation \>=95% were reported in this outcome measure. |
| Plasma Concentration Versus Time Summary of PF-07321332 | Day 1: 1 hour post dose; Day 5: 0 minutes pre-dose | — |
| Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Baseline, Days 3, 5, 10 and 14 | Nasal samples were collected to estimate the viral load in participants in terms of logarithm to base 10 (log10) copies per milliliter. |
| Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | From Day 1 to Day 28 | Sustained alleviation of targeted COVID-19 signs/symptoms was defined as the event occurring on the first 4 consecutive days when all symptoms scored as moderate or severe at the time of enrollment were scored as mild or absent and those scored mild or absent at the time of enrollment were scored as absent. Missing severity at baseline was treated as mild. Time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28, was calculated as time (days) from start of study intervention or placebo (Day 1) until sustained alleviation of all targeted COVID-19 associated signs and symptoms. In this outcome measure time to sustained alleviation is reported for each COVID-19 signs and symptoms. |
Countries
Argentina, Brazil, Bulgaria, Colombia, Czechia, Hungary, Japan, Malaysia, Mexico, Poland, Puerto Rico, Romania, Slovakia, South Africa, South Korea, Spain, Thailand, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
Participants who had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by reverse transcription polymerase chain reaction (RT-PCR) within 5 days prior to randomization were included in the study.
Pre-assignment details
A total of 1440 participants signed informed consent form. Out of which, 1296 subjects were randomized and assigned to study drug. 1288 participants were treated and remaining 8 participants were not treated.
Participants by arm
| Arm | Count |
|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5. | 654 |
| Placebo Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5. | 634 |
| Total | 1,288 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 0 | 1 |
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Other | 4 | 2 |
| Overall Study | Withdrawal by Subject | 18 | 17 |
Baseline characteristics
| Characteristic | Nirmatrelvir 300 mg + Ritonavir 100 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 41.76 Years STANDARD_DEVIATION 13.47 | 42.63 Years STANDARD_DEVIATION 13.13 | 42.18 Years STANDARD_DEVIATION 13.31 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 272 Participants | 261 Participants | 533 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 378 Participants | 367 Participants | 745 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 10 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 39 Participants | 32 Participants | 71 Participants |
| Race (NIH/OMB) Asian | 69 Participants | 72 Participants | 141 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants | 23 Participants | 51 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 9 Participants | 15 Participants |
| Race (NIH/OMB) White | 512 Participants | 498 Participants | 1010 Participants |
| Sex: Female, Male Female | 344 Participants | 352 Participants | 696 Participants |
| Sex: Female, Male Male | 310 Participants | 282 Participants | 592 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 654 | 1 / 634 |
| other Total, other adverse events | 120 / 654 | 71 / 634 |
| serious Total, serious adverse events | 8 / 654 | 13 / 634 |
Outcome results
Primary
Time to Sustained Alleviation of Overall COVID-19 Signs and Symptoms Through Day 28
Sustained alleviation of targeted COVID-19 signs/symptoms was defined as the event occurring on the first 4 consecutive days when all symptoms scored as moderate or severe at the time of enrollment were scored as mild or absent and those scored mild or absent at the time of enrollment were scored as absent. Missing severity at baseline was considered as mild. Time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28, was calculated as time (days) from start of study intervention or placebo (Day 1) until sustained alleviation of all targeted COVID-19 associated signs and symptoms. In this outcome measure time to sustained alleviation is reported consolidated for overall COVID-19 signs and symptoms.
Time frame: From Day 1 to Day 28
Population: Modified intent-to-treat (mITT1) population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Overall COVID-19 Signs and Symptoms Through Day 28 | 12.000 Days |
| Placebo | Time to Sustained Alleviation of Overall COVID-19 Signs and Symptoms Through Day 28 | 13.000 Days |
p-value: 0.6027Log Rank
Secondary
Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14
Nasal samples were collected to estimate the viral load in participants in terms of logarithm to base 10 (log10) copies per milliliter.
Time frame: Baseline, Days 3, 5, 10 and 14
Population: mITT1 population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized. Here ''Overall Number of Participants Analyzed''=participants evaluable for this outcome measure and ''number analyzed''= participants evaluable at specified time points.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Day 3 | -2.302 Log 10 copies per milliliter | Standard Error 0.096 |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Day 5 | -3.669 Log 10 copies per milliliter | Standard Error 0.09 |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Day 10 | -4.873 Log 10 copies per milliliter | Standard Error 0.081 |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Day 14 | -5.464 Log 10 copies per milliliter | Standard Error 0.072 |
| Placebo | Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Day 14 | -5.249 Log 10 copies per milliliter | Standard Error 0.075 |
| Placebo | Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Day 3 | -1.565 Log 10 copies per milliliter | Standard Error 0.098 |
| Placebo | Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Day 10 | -4.642 Log 10 copies per milliliter | Standard Error 0.082 |
| Placebo | Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14 | Day 5 | -2.835 Log 10 copies per milliliter | Standard Error 0.093 |
Secondary
Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28
Time frame: From Day 1 to Day 28
Population: mITT1 population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28 | Hospitalization | 0.049 Days | Standard Deviation 0.591 |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28 | ICU | 0.000 Days | Standard Deviation 0 |
| Placebo | Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28 | Hospitalization | 0.181 Days | Standard Deviation 1.787 |
| Placebo | Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28 | ICU | 0.065 Days | Standard Deviation 1.004 |
Secondary
Number of COVID-19 Related Medical Visits Per Day Through Day 28
Number of COVID-19 related medical visits per day were reported in this outcome measure.
Time frame: From Day 1 to Day 28
Population: mITT1 population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Number of COVID-19 Related Medical Visits Per Day Through Day 28 | 0.0010 Medical visits per day |
| Placebo | Number of COVID-19 Related Medical Visits Per Day Through Day 28 | 0.0020 Medical visits per day |
p-value: 0.0971Negative binomial
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation
An AE was defined as 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. An SAE was defined as any untoward medical occurrence at any dose that resulted in any of the following outcomes: death; life-threatening ; required inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity ; congenital anomaly/birth defect; or that was considered as an important medical event. TEAEs were defined as events that started on or after the study medication start date and time. AEs included both serious and all non-serious adverse events. AEs that led to study discontinuation and AEs that led to discontinuation of study intervention and then continued study were also reported in this outcome measure.
Time frame: From start of study intervention (Day 1) up to Day 34
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Participants were analyzed according to the intervention they actually received. A randomized but not treated participant was excluded from the safety analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | TEAEs | 169 Participants |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | AEs led to discontinuation of study | 0 Participants |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | AEs led to discontinue study intervention and continued study | 16 Participants |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | SAEs | 8 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | AEs led to discontinue study intervention and continued study | 5 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | TEAEs | 153 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | SAEs | 13 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation | AEs led to discontinuation of study | 1 Participants |
Secondary
Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28
Percentage of participants with COVID-19 related hospitalization or death from any cause during the first 28 days of the study was estimated using the Kaplan-Meier (KM) method.
Time frame: From Day 1 to Day 28
Population: Modified Intent-To-Treat (mITT1) population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28 | COVID-19 hospitalization | 0.765 Percentage of participants |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28 | Death | 0 Percentage of participants |
| Placebo | Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28 | COVID-19 hospitalization | 1.577 Percentage of participants |
| Placebo | Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28 | Death | 0.158 Percentage of participants |
p-value: 0.1796Normal approximation
Secondary
Percentage of Participants With Death Through Week 24
Percentage of participants with death (all-cause) event were reported in this outcome measure.
Time frame: From Day 1 to Week 24
Population: Modified Intent-To-Treat (mITT1) population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Percentage of Participants With Death Through Week 24 | 0 Percentage of participants |
| Placebo | Percentage of Participants With Death Through Week 24 | 0.2 Percentage of participants |
Secondary
Percentage of Participants With Progression to Worsening Status of COVID-19 Signs and Symptoms
Participants recorded a daily severity rating of their symptom severity over the past 24 hours based on a 4-point scale in which 0 was reported if no symptoms were present; 1 if mild; 2 if moderate; and 3 if severe. Vomiting and diarrhea was rated on a 4-point frequency scale where 0 is reported for no occurrence, 1 (mild) for 1 to 2 times, 2 (moderate) for 3 to 4 times, and 3 (severe) for 5 or greater. Progression to a worsening status for any targeted symptom was based up on increasing severity (i.e. the first time any targeted symptoms worsened after treatment relative to baseline).
Time frame: From Day 1 to Day 28
Population: mITT1 population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized. Here, ''Overall Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Percentage of Participants With Progression to Worsening Status of COVID-19 Signs and Symptoms | 75.463 Percentage of participants |
| Placebo | Percentage of Participants With Progression to Worsening Status of COVID-19 Signs and Symptoms | 78.515 Percentage of participants |
Comparison: Main effects of treatment, geographic region, symptom onset duration (\<=3, \>3), baseline SARS-CoV-2 serology status (positive/negative), vaccination status (complete/not vaccinated) and baseline viral load (\<4 log10 copies/mL, \>=4 log10 copies/mL).p-value: 0.108695% CI: [0.613, 1.05]Regression, Logistic
Secondary
Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5
Percentage of participants with a resting peripheral oxygen saturation \>=95% were reported in this outcome measure.
Time frame: Day 1 and Day 5
Population: mITT1 population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized. Here ''Overall Number of Participants Analyzed''=participants evaluable for this outcome measure and ''number analyzed''= participants evaluable at specified time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5 | Day 1 | 62.500 Percentage of participants |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5 | Day 5 | 94.671 Percentage of participants |
| Placebo | Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5 | Day 1 | 67.857 Percentage of participants |
| Placebo | Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5 | Day 5 | 93.212 Percentage of participants |
p-value: 0.326295% CI: [13.163, 192.472]Breslow-Day Test
Comparison: Odds ratio for Day 5 vs Day 195% CI: [8.36, 59.08]
Secondary
Percentage of Participants With Severe Signs and Symptoms of COVID-19 Through Day 28
Participants recorded a daily severity rating of their symptom severity over the past 24 hours based on a 4-point scale in which 0 was reported if no symptoms were present; 1 if mild; 2 if moderate; and 3 if severe. A participant with severe score for any targeted symptoms post-baseline was counted as severe. Vomiting and diarrhea each was rated on a 4-point frequency scale where 0 was reported for no occurrence, 1 for 1 to 2 times, 2 for 3 to 4 times, and 3 for 5 or greater. Sense of smell and sense of taste each be rated on a 3-point Likert scale where 0 was reported if the sense of smell/taste was the same as usual, 1 if the sense of smell/taste was less than usual, and 2 for no sense of smell/taste.
Time frame: From Day 1 to Day 28
Population: mITT1 population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized. Here, ''Overall Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Percentage of Participants With Severe Signs and Symptoms of COVID-19 Through Day 28 | 19.136 Percentage of participants |
| Placebo | Percentage of Participants With Severe Signs and Symptoms of COVID-19 Through Day 28 | 21.643 Percentage of participants |
Comparison: Main effects of treatment, geographic region, baseline SARS-CoV-2 serology status and baseline viral load (\< 4 log10 copies/mL, \>= 4 log10 copies/mL).p-value: 0.162295% CI: [0.618, 1.084]Regression, Logistic
Secondary
Plasma Concentration Versus Time Summary of PF-07321332
Time frame: Day 1: 1 hour post dose; Day 5: 0 minutes pre-dose
Population: Safety analysis set included all participants who received at least 1 dose of study intervention. Participants were analyzed according to the intervention they actually received. A randomized but not treated participant was excluded from the safety analyses. Here ''Overall Number of Participants Analyzed''=participants evaluable for this outcome measure and ''number analyzed''= participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Plasma Concentration Versus Time Summary of PF-07321332 | Day 1 (1 hour post-dose) | 2437 Nanograms per milliliter | Standard Deviation 1791.3 |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Plasma Concentration Versus Time Summary of PF-07321332 | Day 5 (0 minutes pre-dose) | 3468 Nanograms per milliliter | Standard Deviation 2454.7 |
Secondary
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Sustained alleviation of targeted COVID-19 signs/symptoms was defined as the event occurring on the first 4 consecutive days when all symptoms scored as moderate or severe at the time of enrollment were scored as mild or absent and those scored mild or absent at the time of enrollment were scored as absent. Missing severity at baseline was treated as mild. Time to sustained alleviation of all targeted COVID-19 signs and symptoms through Day 28, was calculated as time (days) from start of study intervention or placebo (Day 1) until sustained alleviation of all targeted COVID-19 associated signs and symptoms. In this outcome measure time to sustained alleviation is reported for each COVID-19 signs and symptoms.
Time frame: From Day 1 to Day 28
Population: mITT1 population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized. Here, ''Number Analyzed'' signifies participants evaluable at specific rows.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Cough | 7.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Stuffy or runny nose | 5.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Feeling hot or feverish | 3.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Sore throat | 4.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Chills or shivering | 3.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Vomit | 3.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Headache | 5.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Muscle or body aches | 5.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Diarrhea | 6.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Shortness of breath or difficulty breathing | 5.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Nausea | 4.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Shortness of breath or difficulty breathing | 6.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Cough | 8.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Diarrhea | 4.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Feeling hot or feverish | 4.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Headache | 5.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Nausea | 4.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Stuffy or runny nose | 7.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Sore throat | 5.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Vomit | 3.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Muscle or body aches | 5.000 Days |
| Placebo | Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28 | Chills or shivering | 3.000 Days |
Secondary
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Sustained resolution was defined as when targeted symptoms are scored as absent for 4 consecutive days. The first day of the 4 consecutive-day period was considered the first event date. In this outcome measure time to sustained resolution is reported consolidated for each COVID-19 signs and symptoms.
Time frame: From Day 1 to Day 28
Population: mITT1 population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized. Here ''Overall Number of Participants Analyzed''=participants evaluable for this outcome measure and ''number analyzed''= participants evaluable at specified time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Muscle or body aches | 8.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Shortness of breath or difficulty breathing | 7.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Chills or shivering | 4.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Cough | 11.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Diarrhea | 6.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Stuffy or runny nose | 9.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Feeling hot or feverish | 4.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Headache | 7.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Nausea | 6.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Sore throat | 6.000 Days |
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Vomit | 3.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Stuffy or runny nose | 10.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Muscle or body aches | 9.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Feeling hot or feverish | 5.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Shortness of breath or difficulty breathing | 8.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Vomit | 3.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Chills or shivering | 5.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Headache | 9.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Cough | 12.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Sore throat | 8.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Diarrhea | 5.000 Days |
| Placebo | Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28 | Nausea | 5.000 Days |
Secondary
Time to Sustained Resolution of Overall COVID-19 Signs and Symptoms Through Day 28
Sustained resolution was defined as when targeted symptoms are scored as absent for 4 consecutive days. The first day of the 4 consecutive-day period was considered the first event date.
Time frame: From Day 1 to Day 28
Population: mITT1 population included all participants randomly assigned to study intervention, who received at least 1 dose of study intervention. Participants were analyzed according to the study intervention they were randomized. In this outcome measure time to sustained resolution is reported consolidated for overall COVID-19 signs and symptoms. Here, ''Overall Number of Participants Analyzed'' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nirmatrelvir 300 mg + Ritonavir 100 mg | Time to Sustained Resolution of Overall COVID-19 Signs and Symptoms Through Day 28 | 15.000 Days |
| Placebo | Time to Sustained Resolution of Overall COVID-19 Signs and Symptoms Through Day 28 | 16.000 Days |
p-value: 0.4298Log Rank