Trial Outcomes & Findings for Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients (EPIC-SR). (NCT NCT05011513)
NCT ID: NCT05011513
Last Updated: 2023-08-14
Results Overview
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.
TERMINATED
PHASE2/PHASE3
1440 participants
From Day 1 to Day 28
2023-08-14
Participant Flow
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.
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.
Participant milestones
| Measure |
Nirmatrelvir 300 Milligram (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
|
Placebo
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Overall Study
STARTED
|
658
|
638
|
|
Overall Study
Treated
|
654
|
634
|
|
Overall Study
COMPLETED
|
632
|
618
|
|
Overall Study
NOT COMPLETED
|
26
|
20
|
Reasons for withdrawal
| Measure |
Nirmatrelvir 300 Milligram (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
|
Placebo
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Lost to Follow-up
|
4
|
0
|
|
Overall Study
Withdrawal by Subject
|
18
|
17
|
|
Overall Study
Other
|
4
|
2
|
Baseline Characteristics
Evaluation of Protease Inhibition for COVID-19 in Standard-Risk Patients (EPIC-SR).
Baseline characteristics by cohort
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
Total
n=1288 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.76 Years
STANDARD_DEVIATION 13.47 • n=5 Participants
|
42.63 Years
STANDARD_DEVIATION 13.13 • n=7 Participants
|
42.18 Years
STANDARD_DEVIATION 13.31 • n=5 Participants
|
|
Sex: Female, Male
Female
|
344 Participants
n=5 Participants
|
352 Participants
n=7 Participants
|
696 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
310 Participants
n=5 Participants
|
282 Participants
n=7 Participants
|
592 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
272 Participants
n=5 Participants
|
261 Participants
n=7 Participants
|
533 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
378 Participants
n=5 Participants
|
367 Participants
n=7 Participants
|
745 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
39 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
71 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
69 Participants
n=5 Participants
|
72 Participants
n=7 Participants
|
141 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
28 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
51 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
512 Participants
n=5 Participants
|
498 Participants
n=7 Participants
|
1010 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From Day 1 to Day 28Population: 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.
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.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Time to Sustained Alleviation of Overall COVID-19 Signs and Symptoms Through Day 28
|
12.000 Days
Interval 11.0 to 13.0
|
13.000 Days
Interval 12.0 to 14.0
|
SECONDARY outcome
Timeframe: From start of study intervention (Day 1) up to Day 34Population: 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.
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.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation
TEAEs
|
169 Participants
|
153 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs and AEs Leading to Study and Study Drug Discontinuation
SAEs
|
8 Participants
|
13 Participants
|
|
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
|
1 Participants
|
|
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
|
5 Participants
|
SECONDARY outcome
Timeframe: From Day 1 to Day 28Population: 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.
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.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28
COVID-19 hospitalization
|
0.765 Percentage of participants
|
1.577 Percentage of participants
|
|
Percentage of Participants With COVID-19 Related Hospitalization or Death From Any Cause Through Day 28
Death
|
0 Percentage of participants
|
0.158 Percentage of participants
|
SECONDARY outcome
Timeframe: From Day 1 to Week 24Population: 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.
Percentage of participants with death (all-cause) event were reported in this outcome measure.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Percentage of Participants With Death Through Week 24
|
0 Percentage of participants
|
0.2 Percentage of participants
|
SECONDARY outcome
Timeframe: From Day 1 to Day 28Population: 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.
Number of COVID-19 related medical visits per day were reported in this outcome measure.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Number of COVID-19 Related Medical Visits Per Day Through Day 28
|
0.0010 Medical visits per day
Interval 0.0005 to 0.0019
|
0.0020 Medical visits per day
Interval 0.001 to 0.0038
|
SECONDARY outcome
Timeframe: From Day 1 to Day 28Population: 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.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28
Hospitalization
|
0.049 Days
Standard Deviation 0.591
|
0.181 Days
Standard Deviation 1.787
|
|
Duration of Hospitalization and Intensive Care Unit (ICU) Stay Through Day 28
ICU
|
0.000 Days
Standard Deviation 0.000
|
0.065 Days
Standard Deviation 1.004
|
SECONDARY outcome
Timeframe: From Day 1 to Day 28Population: 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.
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.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=648 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=633 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Percentage of Participants With Severe Signs and Symptoms of COVID-19 Through Day 28
|
19.136 Percentage of participants
|
21.643 Percentage of participants
|
SECONDARY outcome
Timeframe: From Day 1 to Day 28Population: 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.
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.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=428 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=425 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Time to Sustained Resolution of Overall COVID-19 Signs and Symptoms Through Day 28
|
15.000 Days
Interval 14.0 to 16.0
|
16.000 Days
Interval 15.0 to 17.0
|
SECONDARY outcome
Timeframe: From Day 1 to Day 28Population: 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.
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.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Muscle or body aches
|
5.000 Days
Interval 4.0 to 6.0
|
5.000 Days
Interval 4.0 to 6.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Shortness of breath or difficulty breathing
|
5.000 Days
Interval 4.0 to 6.0
|
6.000 Days
Interval 5.0 to 7.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Chills or shivering
|
3.000 Days
Interval 3.0 to 4.0
|
3.000 Days
Interval 3.0 to 4.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Cough
|
7.000 Days
Interval 6.0 to 8.0
|
8.000 Days
Interval 7.0 to 9.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Diarrhea
|
6.000 Days
Interval 5.0 to 9.0
|
4.000 Days
Interval 3.0 to 6.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Feeling hot or feverish
|
3.000 Days
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.
|
4.000 Days
Interval 3.0 to 4.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Headache
|
5.000 Days
Interval 4.0 to 5.0
|
5.000 Days
Interval 5.0 to 6.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Nausea
|
4.000 Days
Interval 3.0 to 5.0
|
4.000 Days
Interval 3.0 to 5.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Stuffy or runny nose
|
5.000 Days
Interval 4.0 to 6.0
|
7.000 Days
Interval 6.0 to 7.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Sore throat
|
4.000 Days
Interval 4.0 to 5.0
|
5.000 Days
Interval 4.0 to 6.0
|
|
Time to Sustained Alleviation of Each COVID-19 Signs and Symptoms Through Day 28
Vomit
|
3.000 Days
Interval 2.0 to 4.0
|
3.000 Days
Interval 2.0 to 7.0
|
SECONDARY outcome
Timeframe: From Day 1 to Day 28Population: 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.
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.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Muscle or body aches
|
8.000 Days
Interval 7.0 to 9.0
|
9.000 Days
Interval 7.0 to 10.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Shortness of breath or difficulty breathing
|
7.000 Days
Interval 5.0 to 7.0
|
8.000 Days
Interval 7.0 to 11.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Chills or shivering
|
4.000 Days
Interval 3.0 to 5.0
|
5.000 Days
Interval 4.0 to 6.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Cough
|
11.000 Days
Interval 10.0 to 12.0
|
12.000 Days
Interval 11.0 to 13.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Diarrhea
|
6.000 Days
Interval 6.0 to 8.0
|
5.000 Days
Interval 4.0 to 6.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Feeling hot or feverish
|
4.000 Days
Interval 3.0 to 5.0
|
5.000 Days
Interval 5.0 to 6.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Headache
|
7.000 Days
Interval 7.0 to 9.0
|
9.000 Days
Interval 8.0 to 10.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Nausea
|
6.000 Days
Interval 4.0 to 7.0
|
5.000 Days
Interval 4.0 to 7.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Stuffy or runny nose
|
9.000 Days
Interval 7.0 to 10.0
|
10.000 Days
Interval 9.0 to 11.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Sore throat
|
6.000 Days
Interval 6.0 to 7.0
|
8.000 Days
Interval 7.0 to 8.0
|
|
Time to Sustained Resolution of Each COVID-19 Signs and Symptoms Through Day 28
Vomit
|
3.000 Days
Interval 2.0 to 4.0
|
3.000 Days
Interval 2.0 to 7.0
|
SECONDARY outcome
Timeframe: From Day 1 to Day 28Population: 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.
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).
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=648 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=633 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Percentage of Participants With Progression to Worsening Status of COVID-19 Signs and Symptoms
|
75.463 Percentage of participants
|
78.515 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 5Population: 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.
Percentage of participants with a resting peripheral oxygen saturation \>=95% were reported in this outcome measure.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=638 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=604 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
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
|
67.857 Percentage of participants
|
|
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
|
93.212 Percentage of participants
|
SECONDARY outcome
Timeframe: Day 1: 1 hour post dose; Day 5: 0 minutes pre-dosePopulation: 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.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=287 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Plasma Concentration Versus Time Summary of PF-07321332
Day 1 (1 hour post-dose)
|
2437 Nanograms per milliliter
Standard Deviation 1791.3
|
—
|
|
Plasma Concentration Versus Time Summary of PF-07321332
Day 5 (0 minutes pre-dose)
|
3468 Nanograms per milliliter
Standard Deviation 2454.7
|
—
|
SECONDARY outcome
Timeframe: Baseline, Days 3, 5, 10 and 14Population: 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.
Nasal samples were collected to estimate the viral load in participants in terms of logarithm to base 10 (log10) copies per milliliter.
Outcome measures
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=515 Participants
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=493 Participants
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
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
|
-4.642 Log 10 copies per milliliter
Standard Error 0.082
|
|
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
|
-1.565 Log 10 copies per milliliter
Standard Error 0.098
|
|
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 0.090
|
-2.835 Log 10 copies per milliliter
Standard Error 0.093
|
|
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
|
-5.249 Log 10 copies per milliliter
Standard Error 0.075
|
Adverse Events
Nirmatrelvir 300 mg + Ritonavir 100 mg
Placebo
Serious adverse events
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 participants at risk
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 participants at risk
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Infections and infestations
COVID-19
|
0.00%
0/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.16%
1/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Infections and infestations
COVID-19 pneumonia
|
0.46%
3/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
1.3%
8/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Infections and infestations
Pneumonia
|
0.15%
1/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.32%
2/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Infections and infestations
Pneumonia aspiration
|
0.15%
1/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.00%
0/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Infections and infestations
Sepsis
|
0.00%
0/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.16%
1/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Investigations
Creatinine renal clearance decreased
|
0.00%
0/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.16%
1/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Investigations
Hepatic enzyme increased
|
0.15%
1/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.00%
0/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.15%
1/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.00%
0/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer metastatic
|
0.15%
1/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.00%
0/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Nervous system disorders
Multiple sclerosis relapse
|
0.00%
0/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.16%
1/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Nervous system disorders
Osmotic demyelination syndrome
|
0.15%
1/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.00%
0/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.15%
1/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.00%
0/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
Other adverse events
| Measure |
Nirmatrelvir 300 mg + Ritonavir 100 mg
n=654 participants at risk
Participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally every 12 hours from Day 1 to 5.
|
Placebo
n=634 participants at risk
Participants were randomized to receive placebo matched to nirmatrelvir/ritonavir every 12 hours for 10 doses from Day 1 through Day 5.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
4.0%
26/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
3.0%
19/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Gastrointestinal disorders
Dyspepsia
|
1.2%
8/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.32%
2/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Gastrointestinal disorders
Nausea
|
3.2%
21/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
2.7%
17/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Gastrointestinal disorders
Vomiting
|
1.7%
11/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
1.7%
11/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Investigations
Activated partial thromboplastin time prolonged
|
1.1%
7/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
1.9%
12/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Investigations
Alanine aminotransferase increased
|
2.1%
14/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
1.3%
8/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Investigations
Aspartate aminotransferase increased
|
1.4%
9/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.63%
4/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Investigations
Blood thyroid stimulating hormone increased
|
0.61%
4/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
1.1%
7/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Investigations
Fibrin D dimer increased
|
1.2%
8/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
1.4%
9/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Nervous system disorders
Dysgeusia
|
6.7%
44/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
0.47%
3/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
|
Nervous system disorders
Headache
|
0.92%
6/654 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
1.4%
9/634 • SAEs and Non-SAEs: From Day 1 to Week 24; All-cause mortality: till Week 24
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER