Trial Outcomes & Findings for A Study to Learn About the Study Medicines (Nirmatrelvir Plus Ritonavir) in People Aged 12 Years or Older With COVID-19 and a Compromised Immune System (NCT NCT05438602)

NCT ID: NCT05438602

Last Updated: 2024-09-23

Results Overview

NP swab was collected by healthcare professional (HCP) from participants and were sent to the central laboratory for viral RNA level testing real-time reverse transcriptase-polymerase chain reaction(RT-PCR). Sustained was defined as NP swab SARS-CoV-2 RNA level not \>=2.0 log10 per milliliter (copies/mL) at any study visit (through Day 44) following the first study visit where the participant's NP swab SARS-CoV-2 RNA level \<LLOQ (\<2.0 log10 copies/mL).

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 158 participants
• Primary outcome timeframe: From Day 15 to Day 44
• Results posted on: 2024-09-23

Participant Flow

In this study there were following population enrolled: main study population (MSP) and rebound population (RP). MSP: Non-hospitalized participants aged greater than or equal to (>=) 12 years weighing >= 40 kilogram(kg) who were immunocompromised and diagnosed with symptomatic Coronavirus disease 2019 (COVID-19) were enrolled. RP: Non-hospitalized participants with documented, symptomatic COVID-19 rebound within 14 days after 5-day treatment with nirmatrelvir/ritonavir were enrolled.

Participant milestones

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Treatment (15 Days) STARTED	54	52	51
Treatment (15 Days) COMPLETED	50	49	43
Treatment (15 Days) NOT COMPLETED	4	3	8
Follow-up (Through Day 44) STARTED	54	52	51
Follow-up (Through Day 44) COMPLETED	50	50	45
Follow-up (Through Day 44) NOT COMPLETED	4	2	6
Long-term Follow-up (Through Week 24) STARTED	54	52	51
Long-term Follow-up (Through Week 24) COMPLETED	47	47	44
Long-term Follow-up (Through Week 24) NOT COMPLETED	7	5	7

Reasons for withdrawal

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Treatment (15 Days) Adverse Event	2	1	3
Treatment (15 Days) No longer met eligibility criteria	0	1	0
Treatment (15 Days) Other	0	0	1
Treatment (15 Days) Withdrawal by Subject	2	1	4
Follow-up (Through Day 44) Adverse Event	1	0	0
Follow-up (Through Day 44) Withdrawal by Subject	3	2	6
Long-term Follow-up (Through Week 24) Other	1	0	0
Long-term Follow-up (Through Week 24) Lost to Follow-up	1	0	0
Long-term Follow-up (Through Week 24) Death	1	0	1
Long-term Follow-up (Through Week 24) Withdrawal by Subject	4	5	6

Baseline Characteristics

A Study to Learn About the Study Medicines (Nirmatrelvir Plus Ritonavir) in People Aged 12 Years or Older With COVID-19 and a Compromised Immune System

Baseline characteristics by cohort

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=54 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=51 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Total n=157 Participants Total of all reporting groups
Age, Continuous	57.09 Years STANDARD_DEVIATION 14.77 • n=5 Participants	54.77 Years STANDARD_DEVIATION 16.20 • n=7 Participants	55.63 Years STANDARD_DEVIATION 14.44 • n=5 Participants	55.85 Years STANDARD_DEVIATION 15.08 • n=4 Participants
Age, Customized < 12 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Customized 12 - 17 years	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Age, Customized 18 - 44 years	11 Participants n=5 Participants	9 Participants n=7 Participants	11 Participants n=5 Participants	31 Participants n=4 Participants
Age, Customized 45 - 59 years	19 Participants n=5 Participants	19 Participants n=7 Participants	17 Participants n=5 Participants	55 Participants n=4 Participants
Age, Customized 60 - 64 years	4 Participants n=5 Participants	7 Participants n=7 Participants	10 Participants n=5 Participants	21 Participants n=4 Participants
Age, Customized 65 - 74 years	14 Participants n=5 Participants	11 Participants n=7 Participants	8 Participants n=5 Participants	33 Participants n=4 Participants
Age, Customized >= 75 years	6 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	30 Participants n=7 Participants	26 Participants n=5 Participants	84 Participants n=4 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	22 Participants n=7 Participants	25 Participants n=5 Participants	73 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	36 Participants n=5 Participants	33 Participants n=7 Participants	32 Participants n=5 Participants	101 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	19 Participants n=7 Participants	19 Participants n=5 Participants	54 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) White	50 Participants n=5 Participants	47 Participants n=7 Participants	44 Participants n=5 Participants	141 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants

PRIMARY outcome

Timeframe: From Day 15 to Day 44

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

NP swab was collected by healthcare professional (HCP) from participants and were sent to the central laboratory for viral RNA level testing real-time reverse transcriptase-polymerase chain reaction(RT-PCR). Sustained was defined as NP swab SARS-CoV-2 RNA level not >=2.0 log10 per milliliter (copies/mL) at any study visit (through Day 44) following the first study visit where the participant's NP swab SARS-CoV-2 RNA level <LLOQ (<2.0 log10 copies/mL).

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Percentage of Participants With Sustained Nasopharyngeal (NP) Swab Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribonucleic Acid (RNA) < Lower Limit of Quantitation (LLOQ) From Day 15 to Day 44	61.54 Percentage of participants 0.483 • Interval 0.483 to 0.748	70.83 Percentage of participants 0.580 • Interval 0.58 to 0.837	66.00 Percentage of participants 0.529 • Interval 0.529 to 0.791

SECONDARY outcome

Timeframe: Day 1 through Day 44

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure with non-missing data in the analysis set.

An NP swab was collected by HCP from participants and were sent to the central laboratory for viral RNA level testing RT-PCR. The LLOQ is <2.0 log10 copies/mL. Kaplan-Meier method was used for analysis. Time (days) to first NP swab SARS-CoV-2 RNA<LLOQ (event) was calculated as (First Event Date) - (First Dose Date) +1.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=46 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=44 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=45 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Time to First NP Swab SARS-Cov-2 RNA <LLOQ for Participants With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline	9.500 Days 95% Confidence Interval 6.000 • Interval 6.0 to 15.0	11.000 Days 95% Confidence Interval 10.000 • Interval 10.0 to 15.0	9.000 Days 95% Confidence Interval 6.000 • Interval 6.0 to 11.0

SECONDARY outcome

Timeframe: Day 1 through Day 44

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, 'Number of Participants Analyzed' signifies participants evaluable for this outcome measure with non-missing data in the analysis set.

An NP swab was collected by HCP from participants and were sent to the central laboratory for viral RNA level testing RT-PCR. Sustained was defined as NP swab SARS-CoV-2 RNA level not >=2.0 log10 copies/mL at any study visit (through Day 44) following the first study visit where the participant's NP swab SARS-CoV-2 RNA level < LLOQ. The LLOQ is <2.0 log10 copies/mL. Time (days) to first sustained NP swab SARS-CoV-2 RNA<LLOQ (event) was calculated as (First Event Date) - (First Dose Date) +1.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=46 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=44 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=45 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Time to First Sustained NP Swab SARS-CoV-2 RNA < LLOQ for Participants Through Day 44 With NP Swab SARS-CoV-2 RNA >= LLOQ at Baseline	15.000 Days 95% Confidence Interval 9.000 • Interval 9.0 to 16.0	11.000 Days 95% Confidence Interval 10.000 • Interval 10.0 to 15.0	10.000 Days 95% Confidence Interval 9.000 • Interval 9.0 to 16.0

SECONDARY outcome

Timeframe: Baseline; Days 5, 10, 15, 21, 28, 35, and 44; Weeks 12 and 24

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

A 6-mL blood sample was collected for adult and pediatric participants and was analyzed to measure SARS-CoV-2 RNA <LLOQ in Plasma by RT-PCR. The LLOQ is <2.0 log10 copies/mL.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Baseline	98.08 Percentage of participants 0.930 • Interval 0.93 to 1.0	97.92 Percentage of participants 0.925 • Interval 0.925 to 1.0	92.00 Percentage of participants 0.923 • Interval 0.923 to 1.0
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Day 5	90.38 Percentage of participants 0.925 • Interval 0.925 to 1.0	93.75 Percentage of participants 0.921 • Interval 0.921 to 1.0	92.00 Percentage of participants 0.923 • Interval 0.923 to 1.0
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Day 10	92.31 Percentage of participants 0.926 • Interval 0.926 to 1.0	95.83 Percentage of participants 0.923 • Interval 0.923 to 1.0	92.00 Percentage of participants 0.923 • Interval 0.923 to 1.0
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Day 15	88.46 Percentage of participants 0.923 • Interval 0.923 to 1.0	91.67 Percentage of participants 0.920 • Interval 0.92 to 1.0	88.00 Percentage of participants 0.920 • Interval 0.92 to 1.0
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Day 21	86.54 Percentage of participants 0.921 • Interval 0.921 to 1.0	93.75 Percentage of participants 0.921 • Interval 0.921 to 1.0	88.00 Percentage of participants 0.920 • Interval 0.92 to 1.0
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Day 28	84.62 Percentage of participants 0.920 • Interval 0.92 to 1.0	95.83 Percentage of participants 0.923 • Interval 0.923 to 1.0	78.00 Percentage of participants 0.910 • Interval 0.91 to 1.0
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Day 35	82.69 Percentage of participants 0.918 • Interval 0.918 to 1.0	93.75 Percentage of participants 0.921 • Interval 0.921 to 1.0	84.00 Percentage of participants 0.916 • Interval 0.916 to 1.0
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Day 44	86.54 Percentage of participants 0.921 • Interval 0.921 to 1.0	91.67 Percentage of participants 0.920 • Interval 0.92 to 1.0	88.00 Percentage of participants 0.920 • Interval 0.92 to 1.0
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Week 12	73.08 Percentage of participants	87.50 Percentage of participants	78.00 Percentage of participants
Percentage of Participants With SARS-CoV-2 RNA < LLOQ in Plasma Over Time at Each Visit Through Week 24 Week 24	69.23 Percentage of participants	85.42 Percentage of participants	84.00 Percentage of participants

SECONDARY outcome

Timeframe: Baseline; Days 5, 10, 15, 21, 28, 35 and 44

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

An NP swab was collected by HCP from adult and pediatric participants and were sent to the central laboratory for viral RNA level testing RT-PCR. The LLOQ is <2.0 log10 copies/mL.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 Baseline	5.77 Percentage of participants 0.292 • Interval 0.292 to 1.0	8.33 Percentage of participants 0.398 • Interval 0.398 to 1.0	4.00 Percentage of participants 0.158 • Interval 0.158 to 1.0
Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 Day 5	38.46 Percentage of participants 0.832 • Interval 0.832 to 1.0	29.17 Percentage of participants 0.768 • Interval 0.768 to 1.0	38.00 Percentage of participants 0.824 • Interval 0.824 to 1.0
Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 Day 10	51.92 Percentage of participants 0.872 • Interval 0.872 to 1.0	64.58 Percentage of participants 0.888 • Interval 0.888 to 1.0	58.00 Percentage of participants 0.881 • Interval 0.881 to 1.0
Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 Day 15	69.23 Percentage of participants 0.903 • Interval 0.903 to 1.0	77.08 Percentage of participants 0.905 • Interval 0.905 to 1.0	72.00 Percentage of participants 0.903 • Interval 0.903 to 1.0
Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 Day 21	71.15 Percentage of participants 0.905 • Interval 0.905 to 1.0	91.67 Percentage of participants 0.920 • Interval 0.92 to 1.0	78.00 Percentage of participants 0.910 • Interval 0.91 to 1.0
Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 Day 28	80.77 Percentage of participants 0.916 • Interval 0.916 to 1.0	93.75 Percentage of participants 0.921 • Interval 0.921 to 1.0	76.00 Percentage of participants 0.907 • Interval 0.907 to 1.0
Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 Day 35	80.77 Percentage of participants 0.916 • Interval 0.916 to 1.0	91.67 Percentage of participants 0.920 • Interval 0.92 to 1.0	84.00 Percentage of participants 0.916 • Interval 0.916 to 1.0
Percentage of Participants With SARS-CoV-2 RNA <LLOQ in NP Swabs at Each Study Visit Through Day 44 Day 44	78.85 Percentage of participants 0.914 • Interval 0.914 to 1.0	91.67 Percentage of participants 0.920 • Interval 0.92 to 1.0	88.00 Percentage of participants 0.920 • Interval 0.92 to 1.0

SECONDARY outcome

Timeframe: Baseline; Days 5, 10, 15, 21, 28, 35 and 44

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here "Number of Participants Analyzed" were participants evaluable for this outcome measure. All participants reported under "Number of Participants Analyzed" contributed data to table but may not have evaluable data for every row. Here, "number analyzed" signifies participants with non-missing data in the analysis set and evaluable at specified time points.

An NP swab was collected by HCP from adult and pediatric participants and were sent to the central laboratory for viral RNA level testing RT-PCR.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 5	-3.449 log10 copies/mL Standard Deviation 1.730	-3.621 log10 copies/mL Standard Deviation 1.521	-3.746 log10 copies/mL Standard Deviation 1.687
Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 10	-4.167 log10 copies/mL Standard Deviation 2.292	-4.931 log10 copies/mL Standard Deviation 1.899	-5.002 log10 copies/mL Standard Deviation 1.942
Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 15	-4.827 log10 copies/mL Standard Deviation 2.476	-5.773 log10 copies/mL Standard Deviation 1.473	-6.009 log10 copies/mL Standard Deviation 2.093
Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 21	-5.472 log10 copies/mL Standard Deviation 2.028	-6.328 log10 copies/mL Standard Deviation 1.472	-6.319 log10 copies/mL Standard Deviation 1.967
Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 28	-5.938 log10 copies/mL Standard Deviation 2.138	-6.509 log10 copies/mL Standard Deviation 1.571	-6.530 log10 copies/mL Standard Deviation 1.770
Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 35	-6.237 log10 copies/mL Standard Deviation 1.746	-6.596 log10 copies/mL Standard Deviation 1.453	-6.633 log10 copies/mL Standard Deviation 1.816
Change From Baseline in SARS-CoV-2 RNA Level in NP Swabs at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 44	-5.916 log10 copies/mL Standard Deviation 1.865	-6.597 log10 copies/mL Standard Deviation 1.445	-6.707 log10 copies/mL Standard Deviation 1.922

SECONDARY outcome

Timeframe: Baseline; Days 5, 10, 15, 21, 28, 35 and 44

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure. Here, "Number Analyzed" signifies participants with non-missing data in the analysis set and evaluable at specified time points.

A 6-mL blood sample was collected for adult and pediatric participants and was analyzed to measure SARS-CoV-2 RNA by RT-PCR.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=8 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=10 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=15 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 35	-1.700 log10 copies/mL Standard Deviation 0.000	-1.700 log10 copies/mL Standard Deviation 0.000	-1.894 log10 copies/mL Standard Deviation 0.392
Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 44	-1.700 log10 copies/mL Standard Deviation 0.000	-1.700 log10 copies/mL Standard Deviation 0.000	-1.880 log10 copies/mL Standard Deviation 0.380
Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 5	-1.457 log10 copies/mL Standard Deviation 0.643	-1.360 log10 copies/mL Standard Deviation 0.717	-1.528 log10 copies/mL Standard Deviation 0.626
Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 10	-1.487 log10 copies/mL Standard Deviation 0.601	-1.700 log10 copies/mL Standard Deviation 0.000	-1.880 log10 copies/mL Standard Deviation 0.380
Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 15	-1.700 log10 copies/mL Standard Deviation 0.000	-1.700 log10 copies/mL Standard Deviation 0.000	-1.880 log10 copies/mL Standard Deviation 0.380
Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 21	-1.700 log10 copies/mL Standard Deviation 0.000	-1.700 log10 copies/mL Standard Deviation 0.000	-1.880 log10 copies/mL Standard Deviation 0.380
Change From Baseline in SARS-CoV-2 RNA Level in Plasma at Days 5, 10, 15, 21, 28, 35 and 44 Change at Day 28	-1.700 log10 copies/mL Standard Deviation 0.000	-1.700 log10 copies/mL Standard Deviation 0.000	-1.910 log10 copies/mL Standard Deviation 0.405

SECONDARY outcome

Timeframe: Day 16 through Day 44

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Rebound in SARS-CoV-2 RNA level in NP swabs at follow up (ie, any study visit after end of treatment through Day 44) was defined as a half (0.5) log10 copies/mL increase or greater in SARS-CoV-2 RNA level relative to end of treatment SARS-CoV-2 RNA level based on treatment regimen, with a follow-up viral RNA level >= 2.5 log10 copies/mL.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Number of Participants With Rebound in SARS-CoV-2 RNA Level in NP Swabs at Follow up	9 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 of dosing up to Week 24

Population: Safety population included all randomized participants who received at least 1 dose of the study intervention.

An adverse event (AE) was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAE was an AE that occurred after initiation of study treatment that was not present at the time of treatment start or an AE that increased in severity after the initiation of medication, if the event was present at the time of treatment start emerges. SAE was an AE resulting in any of the following outcomes or considered medically significant: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or birth defect.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=54 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=51 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Treatment Discontinuation SAEs	5 Participants	1 Participants	4 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Treatment Discontinuation TEAEs	28 Participants	34 Participants	31 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events (AEs) Leading to Treatment Discontinuation AEs Leading to Study Treatment Discontinuation	1 Participants	1 Participants	4 Participants

SECONDARY outcome

Timeframe: Day 1 through Day 28

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Hospitalization >24 h is defined as >24h of acute care in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with severe COVID-19. This included specialized acute medical care unit within an assisted living facility or nursing home. This did not include hospitalization for the purposes of public health and/or clinical trial execution.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Percentage of Participants With COVID-19-Related Hospitalization >24 Hours (h) or Death Through Day 28 Hospitalization	3.846 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With COVID-19-Related Hospitalization >24 Hours (h) or Death Through Day 28 Death	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 through Week 24

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Death due to any cause through week 24 was considered. Kaplan-Meier method was used for evaluation.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Percentage of Participants With Death Through Week 24	1.923 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 through Day 44 and Day 1 through Week 24

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

COVID-19 related hospitalization is defined as >24h of acute care in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with severe COVID-19. This included specialized acute medical care unit within an assisted living facility or nursing home. This did not include hospitalization for the purposes of public health and/or clinical trial execution.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Percentage of Participants With COVID-19-Related Hospitalization Through Day 44 and Week 24 Through Day 44	3.846 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With COVID-19-Related Hospitalization Through Day 44 and Week 24 Through Week 24	3.846 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 through Day 44 and Day 1 through Week 24

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Percentage of Participants With COVID-19-Related Intensive Care Unit (ICU) Admission Through Day 44 and Week 24 Through Day 44	1.923 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With COVID-19-Related Intensive Care Unit (ICU) Admission Through Day 44 and Week 24 Through Week 24	1.923 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 through Day 44 and Day 1 through Week 24

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Invasive mechanical ventilation or ECMO were types of oxygen support received in hospital.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Percentage of Participants With Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Through Day 44 and Week 24 Through Day 44	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With Invasive Mechanical Ventilation or Extracorporeal Membrane Oxygenation (ECMO) Through Day 44 and Week 24 Through Week 24	0 Percentage of participants	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Day 1 through Day 44 and Day 1 through Week 24

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Hospitalization >24 hours is defined as >24h of acute care in a hospital or similar acute care facility, including emergency rooms or temporary facilities instituted to address medical needs of those with severe COVID-19.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Mean Number of Days in Hospital and ICU Stay Through Day 44 and Through Week 24 Hospital Stay: Up to Day 44	0.635 Days Standard Deviation 3.453 • Interval 3.453 to	0.000 Days Standard Deviation 0.000 • Interval 0.0 to	0.000 Days Standard Deviation 0.000 • Interval 0.0 to
Mean Number of Days in Hospital and ICU Stay Through Day 44 and Through Week 24 Hospital Stay: Up to Week 24	0.635 Days Standard Deviation 3.453 • Interval 3.453 to	0.000 Days Standard Deviation 0.000 • Interval 0.0 to	0.000 Days Standard Deviation 0.000 • Interval 0.0 to
Mean Number of Days in Hospital and ICU Stay Through Day 44 and Through Week 24 ICU Stay: Up to Day 44	0.442 Days Standard Deviation 3.190 • Interval 3.19 to	0.000 Days Standard Deviation 0.000 • Interval 0.0 to	0.000 Days Standard Deviation 0.000 • Interval 0.0 to
Mean Number of Days in Hospital and ICU Stay Through Day 44 and Through Week 24 ICU Stay: Up to Week 24	0.442 Days Standard Deviation 3.190 • Interval 3.19 to	0.000 Days Standard Deviation 0.000 • Interval 0.0 to	0.000 Days Standard Deviation 0.000 • Interval 0.0 to

SECONDARY outcome

Timeframe: Day 1 through Day 44 and Day 1 through Week 24

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Mean Number of COVID-19-Related Medical Visits Through Day 44 and Through Week 24 Through Day 44	0.115 Medical visits Standard Deviation 0.615 • Interval 0.615 to	0.000 Medical visits Standard Deviation 0.000 • Interval 0.0 to	0.000 Medical visits Standard Deviation 0.000 • Interval 0.0 to
Mean Number of COVID-19-Related Medical Visits Through Day 44 and Through Week 24 Through Week 24	0.115 Medical visits Standard Deviation 0.615 • Interval 0.615 to	0.000 Medical visits Standard Deviation 0.000 • Interval 0.0 to	0.020 Medical visits Standard Deviation 0.141 • Interval 0.141 to

SECONDARY outcome

Timeframe: Day 1 through Day 44

Population: Evaluable analysis set analyzed. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure. All participants reported under "Number of Participants Analyzed"' contributed data to table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants with non-missing data and with baseline severity of mild, moderate and severe of targeted signs/symptoms.

Symptoms alleviation through day44 of each targeted COVID-19 sign/symptom was defined as first time when each targeted symptom scored as moderate/severe at study entry are scored as mild or absent and a targeted symptom scored mild or absent at study entry are scored as absent.COVID-19 targeted signs/symptoms were muscle or body aches,shortness of breath(SOB)or difficulty breathing,chills or shivering, cough,diarrhea,feeling hot or feverish,headache,nausea,stuffy or runny nose,sense of smell,sense of taste,sore throat,low energy or tiredness, vomit.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Chills or shivering	5.000 Days Interval 4.0 to 6.0	4.000 Days Interval 4.0 to 5.0	5.000 Days Interval 4.0 to 5.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 SOB or difficulty breathing	6.000 Days Interval 4.0 to 9.0	9.000 Days Interval 4.0 to 9.0	6.000 Days Interval 4.0 to 13.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Muscle or body aches	6.000 Days Interval 4.0 to 9.0	9.000 Days Interval 4.0 to 9.0	9.000 Days Interval 5.0 to 13.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Cough	6.000 Days Interval 5.0 to 9.0	9.000 Days Interval 6.0 to 9.0	10.000 Days Interval 5.0 to 13.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Diarrhea	9.000 Days Interval 5.0 to 10.0	5.000 Days Interval 4.0 to 9.0	9.000 Days Interval 4.0 to 22.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Feeling hot or feverish	5.000 Days Interval 4.0 to 6.0	4.000 Days Interval 4.0 to 5.0	5.000 Days Interval 4.0 to 5.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Headache	9.000 Days Interval 4.0 to 15.0	5.000 Days Interval 4.0 to 9.0	5.000 Days Interval 4.0 to 9.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Nausea	9.000 Days Interval 4.0 to 13.0	4.000 Days Interval 4.0 to 5.0	6.000 Days Interval 4.0 to 13.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Stuffy or runny nose	9.000 Days Interval 6.0 to 11.0	9.000 Days Interval 5.0 to 9.0	9.000 Days Interval 5.0 to 10.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Sense of smell	9.000 Days Interval 6.0 to 10.0	9.000 Days Interval 4.0 to 10.0	9.000 Days Interval 5.0 to 10.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Sense of taste	10.000 Days Interval 5.0 to 10.0	9.000 Days Interval 4.0 to 10.0	9.000 Days Interval 6.0 to 13.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Sore throat	6.000 Days Interval 4.0 to 6.0	5.000 Days Interval 4.0 to 9.0	5.000 Days Interval 4.0 to 9.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Low energy or tiredness	9.000 Days Interval 6.0 to 13.0	9.000 Days Interval 5.0 to 10.0	9.000 Days Interval 5.0 to 14.0
Time to First Alleviation of Each Targeted Signs and Symptoms Through Day 44 Vomit	6.000 Days Interval 4.0 to The upper limit of CI could not be estimated due to insufficient number of participants with event.	4.000 Days The number of participants response in the participant's diary and participants with events available were not sufficient for calculation of the limits using Kaplan-Meier method	4.500 Days Interval 4.0 to The upper limit of CI could not be estimated due to insufficient number of participants with event.

SECONDARY outcome

Timeframe: Day 1 through Day 44

Population: Evaluable analysis set analyzed. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure. All participants reported under "Number of Participants Analyzed"' contributed data to table but may not have evaluable data for every row. Here, "Number Analyzed" signifies number of participants with non-missing data and with baseline severity of mild, moderate and severe of targeted signs and symptoms.

Symptoms resolution through day 44 of each targeted COVID-19 sign/symptom was defined as the first time when each targeted symptom scored as mild, moderate or severe at study entry are scored as absent. COVID -19 targeted signs/symptoms were muscle or body aches, SOB or difficulty breathing, chills or shivering, cough, diarrhoea, feeling hot or feverish, headache, nausea, stuffy or runny nose, sense of smell, sense of taste, sore throat, low energy or tiredness, vomit.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Sore throat	9.000 Days Interval 5.0 to 11.0	9.500 Days Interval 9.0 to 13.0	9.000 Days Interval 9.0 to 10.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Sense of taste	10.000 Days Interval 9.0 to 14.0	10.500 Days Interval 9.0 to 21.0	10.000 Days Interval 6.0 to 13.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Low energy or tiredness	27.000 Days Interval 13.0 to 33.0	20.000 Days Interval 13.0 to 35.0	22.000 Days Interval 15.0 to The upper limit of CI could not be estimated due to insufficient number of participants with event.
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Vomit	6.000 Days Interval 4.0 to The upper limit of CI could not be estimated due to insufficient number of participants with event.	4.000 Days Interval 4.0 to The upper limit of CI could not be estimated due to insufficient number of participants with event.	4.500 Days Interval 4.0 to The upper limit of CI could not be estimated due to insufficient number of participants with event.
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Muscle or body aches	14.500 Days Interval 10.0 to 19.0	11.000 Days Interval 9.0 to 21.0	10.000 Days Interval 6.0 to 20.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 SOB or difficulty breathing	9.000 Days Interval 5.0 to 13.0	9.500 Days Interval 9.0 to 19.0	12.000 Days Interval 6.0 to 19.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Chills or shivering	6.000 Days Interval 4.0 to 9.0	4.000 Days Interval 4.0 to 9.0	5.000 Days Interval 4.0 to 6.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Cough	13.000 Days Interval 10.0 to 20.0	12.000 Days Interval 9.0 to 21.0	19.500 Days Interval 11.0 to 22.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Diarrhea	9.000 Days Interval 6.0 to 10.0	9.000 Days Interval 4.0 to 13.0	16.500 Days Interval 4.0 to 26.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Feeling hot or feverish	9.000 Days Interval 5.0 to 9.0	7.000 Days Interval 4.0 to 9.0	5.000 Days Interval 4.0 to 6.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Headache	13.000 Days Interval 9.0 to 15.0	10.000 Days Interval 9.0 to 15.0	9.000 Days Interval 5.0 to 11.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Nausea	9.000 Days Interval 4.0 to 14.0	4.000 Days Interval 4.0 to 9.0	9.000 Days Interval 4.0 to 13.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Stuffy or runny nose	14.000 Days Interval 10.0 to 22.0	13.000 Days Interval 9.0 to 15.0	13.000 Days Interval 9.0 to 16.0
Time to First Resolution of Each Targeted Signs and Symptoms Through Day 44 Sense of smell	10.000 Days Interval 9.0 to 15.0	9.000 Days Interval 5.0 to 11.0	9.000 Days Interval 5.0 to 10.0

SECONDARY outcome

Timeframe: Day 1 through Day 44

Population: Evaluable analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.

COVID-19 targeted signs/symptoms were muscle or body aches, SOB or difficulty breathing, chills or shivering, cough, diarrhea, feeling hot or feverish, headache, nausea, stuffy or runny nose, sense of smell, sense of taste, sore throat, low energy or tiredness, vomit.

Outcome measures

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=52 Participants Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=48 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=50 Participants Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Percentage of Participants With Any Severe Targeted Signs and Symptoms Attributed to COVID-19 Through Day 44	28.85 Percentage of participants	31.25 Percentage of participants	38.00 Percentage of participants

Adverse Events

Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day

Serious events: 5 serious events

Other events: 12 other events

Deaths: 1 deaths

Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Nirmatrelvir + Ritonavir 15 Day

Serious events: 4 serious events

Other events: 19 other events

Deaths: 1 deaths

Serious adverse events

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=54 participants at risk Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=52 participants at risk Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=51 participants at risk Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/54 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	2.0% 1/51 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Nervous system disorders Haemorrhage intracranial	0.00% 0/54 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	2.0% 1/51 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Gastrointestinal disorders Intestinal obstruction	1.9% 1/54 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/51 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Infections and infestations COVID-19	1.9% 1/54 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/51 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Infections and infestations Fungal infection	0.00% 0/54 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	1.9% 1/52 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/51 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Infections and infestations Pneumonia	0.00% 0/54 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	2.0% 1/51 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Infections and infestations Pseudomonas infection	0.00% 0/54 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	2.0% 1/51 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Infections and infestations Urinary tract infection	1.9% 1/54 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/51 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Follicular lymphoma	1.9% 1/54 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/51 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
General disorders Pyrexia	1.9% 1/54 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/51 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Other adverse events

Measure	Nirmatrelvir + Ritonavir 5 Day Then Placebo 10 Day n=54 participants at risk Eligible participants were randomized to receive nirmatrelvir 300 milligram (mg) and ritonavir 100 mg orally every 12 hours (q12h) for 5 days. Participants with estimated glomerular filtration rate (eGFR) \>=30 to less than (\<) 60 milliliters per minute (mL/min)/1.73 square meter (m\^2) or estimated creatinine clearance (eCrCl) \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 5 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 10 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 10 Day Then Placebo 5 Day n=52 participants at risk Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 10 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 10 days. Participants then received placebo for nirmatrelvir and placebo for ritonavir q12h for next 5 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.	Nirmatrelvir + Ritonavir 15 Day n=51 participants at risk Eligible participants were randomized to receive nirmatrelvir 300 mg and ritonavir 100 mg orally q12h for 5 days. Participants with eGFR \>=30 to \<60 mL/min/1.73 m\^2 or eCrCl \>=30 to \<60 mL/min received nirmatrelvir 150 mg and ritonavir 100 mg orally q12h for 15 days. Participants had follow-up through Day 44. Participants had long term follow-up through Week 24.
Investigations Blood thyroid stimulating hormone increased	0.00% 0/54 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	0.00% 0/52 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	5.9% 3/51 • Number of events 3 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Nervous system disorders Dysgeusia	11.1% 6/54 • Number of events 6 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	23.1% 12/52 • Number of events 12 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	27.5% 14/51 • Number of events 14 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Nervous system disorders Headache	1.9% 1/54 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	5.8% 3/52 • Number of events 4 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	2.0% 1/51 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Gastrointestinal disorders Diarrhoea	9.3% 5/54 • Number of events 5 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	7.7% 4/52 • Number of events 4 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	7.8% 4/51 • Number of events 5 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
Gastrointestinal disorders Nausea	1.9% 1/54 • Number of events 1 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	3.8% 2/52 • Number of events 2 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.	9.8% 5/51 • Number of events 5 • Day 1 of dosing up to Week 24 Safety analysis set included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention.

Additional Information

Pfizer Inc.

Pfizer ClinicalTrials.gov Call Center

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquires@pfizer.com

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