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Trial record 1 of 1 for:    NCT05011513
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Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients (EPIC-SR).

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ClinicalTrials.gov Identifier: NCT05011513
Recruitment Status : Terminated (Enrollment ceased due to a very low rate of hospitalization or death observed in the standard-risk patient population)
First Posted : August 18, 2021
Results First Posted : August 14, 2023
Last Update Posted : August 14, 2023
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition COVID-19
Interventions Drug: PF-07321332
Drug: Ritonavir
Drug: Placebo
Enrollment 1440
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.
Arm/Group Title Nirmatrelvir 300 Milligram (mg) + Ritonavir 100 mg Placebo
Hide Arm/Group Description Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5 Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Period Title: Overall Study
Started 658 638
Treated 654 634
Completed 632 618
Not Completed 26 20
Reason Not Completed
Death             0             1
Lost to Follow-up             4             0
Withdrawal by Subject             18             17
Other             4             2
Arm/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo Total
Hide Arm/Group Description Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5. Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5. Total of all reporting groups
Overall Number of Baseline Participants 654 634 1288
Hide Baseline Analysis Population Description
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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 654 participants 634 participants 1288 participants
41.76  (13.47) 42.63  (13.13) 42.18  (13.31)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 654 participants 634 participants 1288 participants
Female
344
  52.6%
352
  55.5%
696
  54.0%
Male
310
  47.4%
282
  44.5%
592
  46.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 654 participants 634 participants 1288 participants
Hispanic or Latino
272
  41.6%
261
  41.2%
533
  41.4%
Not Hispanic or Latino
378
  57.8%
367
  57.9%
745
  57.8%
Unknown or Not Reported
4
   0.6%
6
   0.9%
10
   0.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 654 participants 634 participants 1288 participants
American Indian or Alaska Native
39
   6.0%
32
   5.0%
71
   5.5%
Asian
69
  10.6%
72
  11.4%
141
  10.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
28
   4.3%
23
   3.6%
51
   4.0%
White
512
  78.3%
498
  78.5%
1010
  78.4%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
6
   0.9%
9
   1.4%
15
   1.2%
1.Primary Outcome
Title Time to Sustained Alleviation of Overall COVID-19 Signs and Symptoms Through Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 654 634
Median (95% Confidence Interval)
Unit of Measure: Days
12.000
(11.000 to 13.000)
13.000
(12.000 to 14.000)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nirmatrelvir 300 mg + Ritonavir 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6027
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 654 634
Measure Type: Count of Participants
Unit of Measure: Participants
TEAEs
169
  25.8%
153
  24.1%
SAEs
8
   1.2%
13
   2.1%
AEs led to discontinuation of study
0
   0.0%
1
   0.2%
AEs led to discontinue study intervention and continued study
16
   2.4%
5
   0.8%
3.Secondary Outcome
Title Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 654 634
Measure Type: Number
Unit of Measure: Percentage of participants
COVID-19 hospitalization 0.765 1.577
Death 0 0.158
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nirmatrelvir 300 mg + Ritonavir 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1796
Comments P-value reported for COVID-19 hospitalization and death due to any cause.
Method Normal approximation
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Death Through Week 24
Hide Description Percentage of participants with death (all-cause) event were reported in this outcome measure.
Time Frame From Day 1 to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 654 634
Measure Type: Number
Unit of Measure: Percentage of participants
0 0.2
5.Secondary Outcome
Title Number of COVID-19 Related Medical Visits Per Day Through Day 28
Hide Description Number of COVID-19 related medical visits per day were reported in this outcome measure.
Time Frame From Day 1 to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 654 634
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Medical visits per day
0.0010
(0.0005 to 0.0019)
0.0020
(0.0010 to 0.0038)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nirmatrelvir 300 mg + Ritonavir 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0971
Comments [Not Specified]
Method Negative binomial
Comments [Not Specified]
6.Secondary Outcome
Title Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28
Hide Description [Not Specified]
Time Frame From Day 1 to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 654 634
Mean (Standard Deviation)
Unit of Measure: Days
Hospitalization 0.049  (0.591) 0.181  (1.787)
ICU 0.000  (0.000) 0.065  (1.004)
7.Secondary Outcome
Title Percentage of Participants With Severe Signs and Symptoms of COVID-19 Through Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 648 633
Measure Type: Number
Unit of Measure: Percentage of participants
19.136 21.643
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nirmatrelvir 300 mg + Ritonavir 100 mg, Placebo
Comments Main effects of treatment, geographic region, baseline SARS-CoV-2 serology status and baseline viral load (< 4 log10 copies/mL, >= 4 log10 copies/mL).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1622
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.819
Confidence Interval (2-Sided) 95%
0.618 to 1.084
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Time to Sustained Resolution of Overall COVID-19 Signs and Symptoms Through Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 428 425
Median (95% Confidence Interval)
Unit of Measure: Days
15.000
(14.000 to 16.000)
16.000
(15.000 to 17.000)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nirmatrelvir 300 mg + Ritonavir 100 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4298
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
9.Secondary Outcome
Title Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 654 634
Median (95% Confidence Interval)
Unit of Measure: Days
Muscle or body aches Number Analyzed 466 participants 449 participants
5.000
(4.000 to 6.000)
5.000
(4.000 to 6.000)
Shortness of breath or difficulty breathing Number Analyzed 222 participants 205 participants
5.000
(4.000 to 6.000)
6.000
(5.000 to 7.000)
Chills or shivering Number Analyzed 318 participants 319 participants
3.000
(3.000 to 4.000)
3.000
(3.000 to 4.000)
Cough Number Analyzed 512 participants 502 participants
7.000
(6.000 to 8.000)
8.000
(7.000 to 9.000)
Diarrhea Number Analyzed 143 participants 117 participants
6.000
(5.000 to 9.000)
4.000
(3.000 to 6.000)
Feeling hot or feverish Number Analyzed 356 participants 350 participants
3.000 [1] 
(NA to NA)
4.000
(3.000 to 4.000)
Headache Number Analyzed 429 participants 424 participants
5.000
(4.000 to 5.000)
5.000
(5.000 to 6.000)
Nausea Number Analyzed 180 participants 165 participants
4.000
(3.000 to 5.000)
4.000
(3.000 to 5.000)
Stuffy or runny nose Number Analyzed 491 participants 484 participants
5.000
(4.000 to 6.000)
7.000
(6.000 to 7.000)
Sore throat Number Analyzed 371 participants 381 participants
4.000
(4.000 to 5.000)
5.000
(4.000 to 6.000)
Vomit Number Analyzed 52 participants 43 participants
3.000
(2.000 to 4.000)
3.000
(2.000 to 7.000)
[1]
Due to variability of data, the number of participants with events available was not sufficient for the calculation of the limits using Kaplan-Meier method.
10.Secondary Outcome
Title Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 654 634
Median (95% Confidence Interval)
Unit of Measure: Days
Muscle or body aches Number Analyzed 466 participants 449 participants
8.000
(7.000 to 9.000)
9.000
(7.000 to 10.000)
Shortness of breath or difficulty breathing Number Analyzed 222 participants 205 participants
7.000
(5.000 to 7.000)
8.000
(7.000 to 11.000)
Chills or shivering Number Analyzed 318 participants 319 participants
4.000
(3.000 to 5.000)
5.000
(4.000 to 6.000)
Cough Number Analyzed 512 participants 502 participants
11.000
(10.000 to 12.000)
12.000
(11.000 to 13.000)
Diarrhea Number Analyzed 143 participants 117 participants
6.000
(6.000 to 8.000)
5.000
(4.000 to 6.000)
Feeling hot or feverish Number Analyzed 356 participants 350 participants
4.000
(3.000 to 5.000)
5.000
(5.000 to 6.000)
Headache Number Analyzed 429 participants 424 participants
7.000
(7.000 to 9.000)
9.000
(8.000 to 10.000)
Nausea Number Analyzed 180 participants 165 participants
6.000
(4.000 to 7.000)
5.000
(4.000 to 7.000)
Stuffy or runny nose Number Analyzed 491 participants 484 participants
9.000
(7.000 to 10.000)
10.000
(9.000 to 11.000)
Sore throat Number Analyzed 371 participants 381 participants
6.000
(6.000 to 7.000)
8.000
(7.000 to 8.000)
Vomit Number Analyzed 52 participants 43 participants
3.000
(2.000 to 4.000)
3.000
(2.000 to 7.000)
11.Secondary Outcome
Title Percentage of Participants With Progression to Worsening Status of COVID-19 Signs and Symptoms
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 648 633
Measure Type: Number
Unit of Measure: Percentage of participants
75.463 78.515
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nirmatrelvir 300 mg + Ritonavir 100 mg, Placebo
Comments 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).
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1086
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.802
Confidence Interval (2-Sided) 95%
0.613 to 1.050
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With Resting Peripheral Oxygen Saturation Greater Than or Equal to (>=) 95% at Day 1 and Day 5
Hide Description Percentage of participants with a resting peripheral oxygen saturation >=95% were reported in this outcome measure.
Time Frame Day 1 and Day 5
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 638 604
Measure Type: Number
Unit of Measure: Percentage of participants
Day 1 Number Analyzed 16 participants 28 participants
62.500 67.857
Day 5 Number Analyzed 638 participants 604 participants
94.671 93.212
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nirmatrelvir 300 mg + Ritonavir 100 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3262
Comments [Not Specified]
Method Breslow-Day Test
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 50.333
Confidence Interval (2-Sided) 95%
13.163 to 192.472
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Odds ratio for Day 5 vs Day 1
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 22.224
Confidence Interval (2-Sided) 95%
8.360 to 59.080
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Plasma Concentration Versus Time Summary of PF-07321332
Hide Description [Not Specified]
Time Frame Day 1: 1 hour post dose; Day 5: 0 minutes pre-dose
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Overall Number of Participants Analyzed 287
Mean (Standard Deviation)
Unit of Measure: Nanograms per milliliter
Day 1 (1 hour post-dose) Number Analyzed 104 participants
2437  (1791.3)
Day 5 (0 minutes pre-dose) Number Analyzed 287 participants
3468  (2454.7)
14.Secondary Outcome
Title Change From Baseline in Logarithm to Base10 (Log10) Transformed Viral Load at Days 3, 5, 10 and 14
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description:
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
Overall Number of Participants Analyzed 515 493
Least Squares Mean (Standard Error)
Unit of Measure: Log 10 copies per milliliter
Day 3 Number Analyzed 515 participants 493 participants
-2.302  (0.096) -1.565  (0.098)
Day 5 Number Analyzed 505 participants 480 participants
-3.669  (0.090) -2.835  (0.093)
Day 10 Number Analyzed 489 participants 478 participants
-4.873  (0.081) -4.642  (0.082)
Day 14 Number Analyzed 508 participants 484 participants
-5.464  (0.072) -5.249  (0.075)
Time Frame SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
Adverse Event Reporting Description Same event may appear as both SAE and non-SAE but are distinct events. An event may be categorized as serious in 1 participant and non-serious in another, or a participant may have experienced both SAE and non-SAE. Safety population comprised of all participants who received at least 1 dose of study intervention during the study.
 
Arm/Group Title Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Hide Arm/Group Description Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5. Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
All-Cause Mortality
Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/654 (0.00%)   1/634 (0.16%) 
Hide Serious Adverse Events
Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   8/654 (1.22%)   13/634 (2.05%) 
Infections and infestations     
COVID-19 * 1  0/654 (0.00%)  1/634 (0.16%) 
COVID-19 pneumonia * 1  3/654 (0.46%)  8/634 (1.26%) 
Pneumonia * 1  1/654 (0.15%)  2/634 (0.32%) 
Pneumonia aspiration * 1  1/654 (0.15%)  0/634 (0.00%) 
Sepsis * 1  0/654 (0.00%)  1/634 (0.16%) 
Investigations     
Creatinine renal clearance decreased * 1  0/654 (0.00%)  1/634 (0.16%) 
Hepatic enzyme increased * 1  1/654 (0.15%)  0/634 (0.00%) 
Metabolism and nutrition disorders     
Electrolyte imbalance * 1  1/654 (0.15%)  0/634 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Colon cancer metastatic * 1  1/654 (0.15%)  0/634 (0.00%) 
Nervous system disorders     
Multiple sclerosis relapse * 1  0/654 (0.00%)  1/634 (0.16%) 
Osmotic demyelination syndrome * 1  1/654 (0.15%)  0/634 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory distress * 1  1/654 (0.15%)  0/634 (0.00%) 
1
Term from vocabulary, MedDRA v25.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Nirmatrelvir 300 mg + Ritonavir 100 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   120/654 (18.35%)   71/634 (11.20%) 
Gastrointestinal disorders     
Diarrhoea * 1  26/654 (3.98%)  19/634 (3.00%) 
Dyspepsia * 1  8/654 (1.22%)  2/634 (0.32%) 
Nausea * 1  21/654 (3.21%)  17/634 (2.68%) 
Vomiting * 1  11/654 (1.68%)  11/634 (1.74%) 
Investigations     
Activated partial thromboplastin time prolonged * 1  7/654 (1.07%)  12/634 (1.89%) 
Alanine aminotransferase increased * 1  14/654 (2.14%)  8/634 (1.26%) 
Aspartate aminotransferase increased * 1  9/654 (1.38%)  4/634 (0.63%) 
Blood thyroid stimulating hormone increased * 1  4/654 (0.61%)  7/634 (1.10%) 
Fibrin D dimer increased * 1  8/654 (1.22%)  9/634 (1.42%) 
Nervous system disorders     
Dysgeusia * 1  44/654 (6.73%)  3/634 (0.47%) 
Headache * 1  6/654 (0.92%)  9/634 (1.42%) 
1
Term from vocabulary, MedDRA v25.0
*
Indicates events were collected by non-systematic assessment
In participant flow, there was discontinuations due to AE, which was captured under "Death" as reason for discontinuation. Adverse event was COVID-19 pneumonia and the participant died due to that event and discontinued study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
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Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer Inc.
Phone: 1-800-718-1021
EMail: ClinicalTrials.gov_Inquiries@pfizer.com
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT05011513    
Other Study ID Numbers: C4671002
2021-002857-28 ( EudraCT Number )
EPIC-SR ( Other Identifier: Alias Study Number )
First Submitted: July 30, 2021
First Posted: August 18, 2021
Results First Submitted: July 20, 2023
Results First Posted: August 14, 2023
Last Update Posted: August 14, 2023