SARS-CoV-2 Infection
Conditions
Keywords
COVID-19, SARS COVID-19
Brief summary
The purpose of the study is to understand the effects and safety of PF-07817883 treatment. The study wants to know how PF-07817883 treatment lowers the level of the virus that causes COVID 19. To understand that samples are collected from adult participants who have the symptoms of COVID 19 but are not hospitalized. The study is seeking for participants who: * are 18 years of age or older at the time of entering the study. * have a positive rapid antigen test within 48 hours before entering the study. Rapid antigen test is a test done to confirm the presence of a specific virus in the body. * have onset of signs or symptoms of COVID-19 within 5 days before entering the study. * have at least 1 of the specified signs or symptoms of COVID-19 present on the day of entering the study. Around 228 participants with a confirmed case of COVID 19 are planned to be taken into the study. Participants will be randomly grouped to receive PF-07817883. Three groups will receive 100, 300, 600mg of PF-07817883 and one of the groups will receive placebo (a pill that doesn't have any medicines) orally every 12 hours for 5 days. The study is going to last up to 5 weeks. This includes the initial period of selecting participants, participants receiving the medicine or the placebo and then a 4-week follow-up period after giving the participants the last medicine. The study team will monitor how each participant is doing with the study treatment during the study.
Interventions
DRUGPF-07817883
Arm 1: low dose Arm 2: medium dose Arm 3: high dose
DRUGPlacebo
Placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Participants ≥18 to \<65 years of age at the time of the Screening Visit. * WOCBP may be enrolled. * All fertile participants must agree to use a highly effective method of contraception. 2. Confirmed SARS-CoV-2 infection as determined by RAT in NP specimen collected within 48 hours prior to randomization. Investigator sites will use test kits that are authorized for use in this study and the test result must be available to confirm eligibility. 3. Initial onset of signs/symptoms attributable to COVID-19 within 5 days prior to the day of randomization and at least 1 of the specified signs/symptoms attributable to COVID-19 present on the day of randomization.
Exclusion criteria
1. Current need for hospitalization or anticipated need for hospitalization within 24h after randomization in the clinical opinion of the site investigator. 2. Known medical history of active liver disease (other than nonalcoholic hepatic steatosis), including chronic or active hepatitis B or C infection, primary biliary cirrhosis, Child-Pugh Class B or Class C, or acute liver failure. 3. History of hypersensitivity or other contraindication to any of the components of the study interventions, as determined by the investigator. 4. Suspected or confirmed concurrent active systemic infection other than COVID-19 that may interfere with the evaluation of response to the study intervention. 5. Immunocompromised with ≥1 of the following: 1. Solid organ (eg, liver, heart, lung or kidney) transplant recipient who is receiving immunosuppressive therapy. 2. Receipt of CAR-T-cell therapy or HCT either within 2 years of transplantation or receiving immunosuppressive therapy. 3. Moderate or severe primary immunodeficiency (eg, DiGeorge syndrome, Wiskott-Aldrich syndrome). 4. Use of at least 1 of the following immune-weakening medications: iii. Has received corticosteroids equivalent to prednisone ≥20 mg daily for at least 14 consecutive days within 30 days prior to study entry. iv. Active treatment causing significant immunosuppression, including alkylating agents, antimetabolites, transplant-related immunosuppressive drugs, cancer chemotherapeutic agents, TNF blockers, or other highly immunosuppressive drugs such as biologics. 5. Hematological malignancy (including leukemia, lymphoma and myeloma) or active immunosuppressive treatment for solid tumor. 6. HIV infection with CD4 cell count \<200 mm3 from known medical history within the past 6 months of screening. 6. known severe renal impairment (eGFR of \<30 mL/min/1.73 m2 within 6 months of the screening visit, using the serum creatinine-based CKD-EPI formula12). 7. Oxygen saturation of \<92% on room air obtained at rest within 24h prior to randomization. 8. Has received or is expected to receive any other antiviral for the treatment of COVID 19, including remdesivir, PAXLOVID, molnupiravir, mAb treatment (within 30 days or 5 half-lives \[whichever is longer\] prior to screening) or received convalescent COVID-19 plasma within 12 months. 9. Expected to receive any dose of a SARS-CoV-2 vaccine within 14 days of randomization or during the study. 10. Current or previous administration with an investigational product (drug or vaccine) within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Authorized or products with conditional approval are not considered investigational. 11. Known prior participation in this trial 12. Known history of any of the following abnormalities in clinical laboratory tests (within past 6 months of the screening visit): * T bili ≥2 × ULN (except for Gilbert's syndrome) * AST or ALT ≥2.5 × ULN * Abs neutrophil count \<1000/mm3.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Logarithm Base 10 (Log10) Transformed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribo Nucleic Acid (RNA) Level on Day 5 | Baseline (Day 1), Day 5 | Change from baseline in SARS-CoV-2 RNA level at Day 5 was analyzed using Mixed Effects Repeated Measures (MMRM) model with fixed effects including treatment, visit, visit by treatment interaction, and baseline viral load. Covariates included days from baseline since symptom onset (\<=3 versus \[vs.\] \>3 days), vaccination status (complete or partial vs. unvaccinated), baseline anti-N serology status and age at screening (years). Participants were excluded from the analysis if baseline viral load was less than 4\*log10 copies/milliliter, missing, or not detected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | From start of study intervention up to 28 days after last dose of study intervention (up to 33 days) | An AE was any untoward medical occurrence in a study participant after administration of a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An adverse event is considered a treatment-emergent adverse event (TEAE) if the event started on or after the study medication start date and time. An SAE was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) or resulted in congenital anomaly/birth defect or was considered an important medical event. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations | From start of study intervention up to 28 days after last dose of study intervention (up to 33 days) | An AE was any untoward medical occurrence in a study participant after administration of a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An adverse event is considered a treatment-emergent adverse event (TEAE) if the event started on or after the study medication start date and time. Participants with an AE record indicating the AE caused permanent discontinuation from the study were reported under discontinuations from study due to TEAEs. Permanent discontinuations from study intervention due to TEAEs included those participants who had an AE record that indicated that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study. |
| Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Baseline (Day 1), Day 3, Day 10 and Day 14 | Change from baseline in SARS-CoV-2 RNA level at Day 3, Day 10 and Day 14 were analyzed using MMRM model with fixed effects including treatment, visit, visit by treatment interaction, and baseline viral load. Covariates included days from baseline since symptom onset (\<=3 vs. \>3 days), vaccination status (complete or partial vs. unvaccinated), baseline anti-N serology status and age at screening (years). Participants were excluded from the analysis if baseline viral load was less than 4\*log10 copies/milliliter, missing, or not detected. |
| Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | From start of study intervention up to 28 days after last dose of study intervention (up to 33 days). | Vital signs included blood pressure and pulse rate and were assessed with the participant in the supine or seated position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Pre-defined criteria for vital sign abnormalities was as systolic blood pressure (millimeter of mercury \[mmHg\]): value \< 90, change \>= 30 increase and change \>= 30 decrease, diastolic blood pressure (mmHg): value \<50; change \>= 20 increase and change \>= 20 decrease, pulse rate (beats per minute \[bpm\]): value \< 40 and value \> 120. |
| Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | From baseline (Day 1) up to Day 10 | Twelve lead ECGs were collected using an ECG machine that automatically calculated heart rate and measured PR interval, QT interval, and QT interval correct by Frederica formula (QTcF). ECG abnormalities included: PR interval (millisecond \[msec\]): value \>=280, change \>40 increase; QT interval aggregate (msec): value \> 500), QTcF interval (450 \< value =\< 480; 480 \< value =\< 500; value \> 500; 30 \< change \<= 60 increase and change \> 60 increase). |
| Number of Participants With Laboratory Test Abnormalities | From start of study intervention up to 28 days after last dose of study intervention (up to 33 days). | The following laboratory parameters were assessed according to pre-specified criteria for abnormalities: a) hematology; hemoglobin (gram per deciliter \[g/dL\]), (less than\[\<\]0.8\*lower limit of normal \[LLN\]), erythrocytes(10\^12/Liter \[L\])(\< 0.8\*LLN), lymphocytes(10\^9/L)(more than\[\>\]1.2\*upper limit of normal \[ULN\]), neutrophils(\> 1.2\*ULN and \< 0.8\*LLN), basophils(10\^9/L)(\> 1.2\*ULN) and eosinophils (10\^9/L)(\> 1.2\*ULN). b) clinical chemistry; bilirubin(mg/dL)(\> 1.5\*ULN), urea nitrogen(mg/dL)(\> 1.3\*ULN), creatinine(mg/dL)(\> 1.3\*ULN), potassium(milli equivalence per millilitre \[mEq/L\], (\< 0.9\*LLN and \> 1.1\*ULN), calcium (mg/dL)(\< 0.9\*LLN), bicarbonate(mEq/L)(\< 0.9\*LLN and \> 1.1\*ULN), glucose (mg/dL)(\> 1.5\*ULN), creatine kinase(units per litre \[U/L) (\> 2.0\* ULN), D-Dimer(nanogram per milliliter\[ng/mL\]), (\>1.5\*ULN) and c)urinalysis; bacteria (low power field \[LPF\]\>20). Number of participants with any laboratory abnormalities meeting pre-specified criteria are reported in this outcome measure. |
Countries
United States
Participant flow
Pre-assignment details
A total of 278 participants were screened, of which 37 failed screening and 1 participant was not randomized due to investigational product shortage at site. A total of 240 participants were randomized and assigned to study intervention.
Participants by arm
| Arm | Count |
|---|---|
| PF-07817883 100mg Participants received PF-07817883, 100 mg orally q12h for 5 days (10 doses total). Participants were followed up for 4 weeks. | 40 |
| PF-07817883 300mg Participants received PF-07817883, 300 mg orally every q12h for 5 days (10 doses total). Participants were followed up for 4 weeks. | 39 |
| PF-07817883 600mg Participants received PF-07817883, 600 mg orally every q12h for 5 days (10 doses total). Participants were followed up for 4 weeks. | 79 |
| Placebo Participants received placebo orally every q12h for 5 days (10 doses total). Participants were followed up for 4 weeks. | 79 |
| Total | 237 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow Up (Up to 4 Weeks) | Withdrawal by Subject | 0 | 0 | 1 | 0 |
| Treatment (Up to 5 Days) | Adverse Event | 0 | 1 | 1 | 0 |
| Treatment (Up to 5 Days) | Non-compliance with study drug | 0 | 0 | 0 | 1 |
| Treatment (Up to 5 Days) | Other | 0 | 1 | 0 | 0 |
| Treatment (Up to 5 Days) | Randomized not treated | 0 | 1 | 1 | 1 |
| Treatment (Up to 5 Days) | Withdrawal by Subject | 1 | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | PF-07817883 100mg | PF-07817883 300mg | PF-07817883 600mg | Placebo | Total |
|---|---|---|---|---|---|
| Age, Continuous | 43.6 Years STANDARD_DEVIATION 12.3 | 41.9 Years STANDARD_DEVIATION 11.31 | 41.4 Years STANDARD_DEVIATION 11.6 | 41.5 Years STANDARD_DEVIATION 12.97 | 41.9 Years STANDARD_DEVIATION 12.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 31 Participants | 63 Participants | 64 Participants | 193 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 8 Participants | 15 Participants | 15 Participants | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 6 Participants | 2 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 12 Participants | 6 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) White | 39 Participants | 35 Participants | 60 Participants | 69 Participants | 203 Participants |
| Sex: Female, Male Female | 23 Participants | 29 Participants | 50 Participants | 45 Participants | 147 Participants |
| Sex: Female, Male Male | 17 Participants | 10 Participants | 29 Participants | 34 Participants | 90 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 39 | 0 / 79 | 0 / 79 |
| other Total, other adverse events | 0 / 40 | 1 / 39 | 2 / 79 | 4 / 79 |
| serious Total, serious adverse events | 0 / 40 | 1 / 39 | 0 / 79 | 0 / 79 |
Outcome results
Primary
Change From Baseline in Logarithm Base 10 (Log10) Transformed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribo Nucleic Acid (RNA) Level on Day 5
Change from baseline in SARS-CoV-2 RNA level at Day 5 was analyzed using Mixed Effects Repeated Measures (MMRM) model with fixed effects including treatment, visit, visit by treatment interaction, and baseline viral load. Covariates included days from baseline since symptom onset (\<=3 versus \[vs.\] \>3 days), vaccination status (complete or partial vs. unvaccinated), baseline anti-N serology status and age at screening (years). Participants were excluded from the analysis if baseline viral load was less than 4\*log10 copies/milliliter, missing, or not detected.
Time frame: Baseline (Day 1), Day 5
Population: The modified full analysis set (MFAS) included all participants in the full analysis set (FAS) who had SARS-CoV-2 RNA level greater than or equal to (\>=) 4\*log10 copies/mL at baseline. Participants were analyzed according to the study intervention to which they were randomized. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| PF-07817883 100mg | Change From Baseline in Logarithm Base 10 (Log10) Transformed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribo Nucleic Acid (RNA) Level on Day 5 | -3.883 Log10 copies/milliliter |
| PF-07817883 300mg | Change From Baseline in Logarithm Base 10 (Log10) Transformed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribo Nucleic Acid (RNA) Level on Day 5 | -4.015 Log10 copies/milliliter |
| PF-07817883 600mg | Change From Baseline in Logarithm Base 10 (Log10) Transformed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribo Nucleic Acid (RNA) Level on Day 5 | -4.380 Log10 copies/milliliter |
| Placebo | Change From Baseline in Logarithm Base 10 (Log10) Transformed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Ribo Nucleic Acid (RNA) Level on Day 5 | -3.213 Log10 copies/milliliter |
p-value: 0.018180% CI: [-1.08, -0.262]Mixed Models Analysis
p-value: 0.012780% CI: [-1.26, -0.344]Mixed Models Analysis
p-value: <0.000180% CI: [-1.506, -0.827]Mixed Models Analysis
Secondary
Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14
Change from baseline in SARS-CoV-2 RNA level at Day 3, Day 10 and Day 14 were analyzed using MMRM model with fixed effects including treatment, visit, visit by treatment interaction, and baseline viral load. Covariates included days from baseline since symptom onset (\<=3 vs. \>3 days), vaccination status (complete or partial vs. unvaccinated), baseline anti-N serology status and age at screening (years). Participants were excluded from the analysis if baseline viral load was less than 4\*log10 copies/milliliter, missing, or not detected.
Time frame: Baseline (Day 1), Day 3, Day 10 and Day 14
Population: The MFAS included all participants in the FAS who had SARS-CoV-2 RNA level \>= 4\*log10 copies/mL at baseline. Participants were analyzed according to the study intervention to which they were randomized. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure. 'Number Analyzed' signifies number of participants evaluable for the specified rows.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| PF-07817883 100mg | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 3 | -2.006 Log10 copies/milliliter |
| PF-07817883 100mg | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 14 | -5.682 Log10 copies/milliliter |
| PF-07817883 100mg | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 10 | -5.027 Log10 copies/milliliter |
| PF-07817883 300mg | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 3 | -2.702 Log10 copies/milliliter |
| PF-07817883 300mg | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 14 | -5.500 Log10 copies/milliliter |
| PF-07817883 300mg | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 10 | -5.085 Log10 copies/milliliter |
| PF-07817883 600mg | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 10 | -5.305 Log10 copies/milliliter |
| PF-07817883 600mg | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 3 | -2.546 Log10 copies/milliliter |
| PF-07817883 600mg | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 14 | -5.826 Log10 copies/milliliter |
| Placebo | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 3 | -1.398 Log10 copies/milliliter |
| Placebo | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 14 | -5.443 Log10 copies/milliliter |
| Placebo | Change From Baseline in Log10 Transformed SARS-CoV-2 RNA Level on Days 3, 10 and 14 | Day 10 | -5.091 Log10 copies/milliliter |
Comparison: Day 3p-value: 0.037880% CI: [-1.046, -0.17]Mixed Models Analysis
Comparison: Day 3p-value: 0.000380% CI: [-1.782, -0.826]Mixed Models Analysis
Comparison: Day 3p-value: <0.000180% CI: [-1.509, -0.788]Mixed Models Analysis
Comparison: Day 10p-value: 0.593180% CI: [-0.287, 0.416]Mixed Models Analysis
Comparison: Day 10p-value: 0.50880% CI: [-0.369, 0.381]Mixed Models Analysis
Comparison: Day 10p-value: 0.169280% CI: [-0.501, 0.073]Mixed Models Analysis
Comparison: Day 14p-value: 0.117280% CI: [-0.497, 0.019]Mixed Models Analysis
Comparison: Day 14p-value: 0.397980% CI: [-0.337, 0.224]Mixed Models Analysis
Comparison: Day 14p-value: 0.010980% CI: [-0.595, -0.17]Mixed Models Analysis
Secondary
Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities
Twelve lead ECGs were collected using an ECG machine that automatically calculated heart rate and measured PR interval, QT interval, and QT interval correct by Frederica formula (QTcF). ECG abnormalities included: PR interval (millisecond \[msec\]): value \>=280, change \>40 increase; QT interval aggregate (msec): value \> 500), QTcF interval (450 \< value =\< 480; 480 \< value =\< 500; value \> 500; 30 \< change \<= 60 increase and change \> 60 increase).
Time frame: From baseline (Day 1) up to Day 10
Population: The SAS included all participants randomly assigned to study intervention and who have taken at least 1 dose of study intervention. Participants were analyzed according to the intervention they actually received. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | PR Interval, value >= 280 (msec) | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | PR Interval, change > 40 increase (msec) | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QT Interval (msec) value >500 | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTcF Interval, 450 < value =< 480 (msec) | 1 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, 480 < value =< 500 (msec) | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, value > 500 (msec) | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, 30 < change <= 60 increase (msec) | 5 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, change > 60 increase (msec) | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, value > 500 (msec) | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, 480 < value =< 500 (msec) | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | PR Interval, change > 40 increase (msec) | 2 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, change > 60 increase (msec) | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, 30 < change <= 60 increase (msec) | 6 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTcF Interval, 450 < value =< 480 (msec) | 1 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QT Interval (msec) value >500 | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | PR Interval, value >= 280 (msec) | 0 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, 30 < change <= 60 increase (msec) | 6 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QT Interval (msec) value >500 | 0 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTcF Interval, 450 < value =< 480 (msec) | 2 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, 480 < value =< 500 (msec) | 0 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, value > 500 (msec) | 0 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, change > 60 increase (msec) | 0 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | PR Interval, value >= 280 (msec) | 0 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | PR Interval, change > 40 increase (msec) | 1 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QT Interval (msec) value >500 | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTcF Interval, 450 < value =< 480 (msec) | 6 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | PR Interval, change > 40 increase (msec) | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | PR Interval, value >= 280 (msec) | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, 480 < value =< 500 (msec) | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, change > 60 increase (msec) | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, 30 < change <= 60 increase (msec) | 9 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria For ECG Abnormalities | QTCF Interval, value > 500 (msec) | 0 Participants |
Secondary
Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities
Vital signs included blood pressure and pulse rate and were assessed with the participant in the supine or seated position with a completely automated device after at least 5 minutes of rest for the participant in a quiet setting without distractions. Pre-defined criteria for vital sign abnormalities was as systolic blood pressure (millimeter of mercury \[mmHg\]): value \< 90, change \>= 30 increase and change \>= 30 decrease, diastolic blood pressure (mmHg): value \<50; change \>= 20 increase and change \>= 20 decrease, pulse rate (beats per minute \[bpm\]): value \< 40 and value \> 120.
Time frame: From start of study intervention up to 28 days after last dose of study intervention (up to 33 days).
Population: The SAS included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the intervention they actually received. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; value < 90 (mmHg) | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; change >= 30 (mmHg) increase | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; change >= 20 (mmHg) increase | 1 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; value <50 (mmHg) | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Pulse rate; value < 40 (bpm) | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; change >= 30 (mmHg) decrease | 1 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; change >= 20 (mmHg) decrease | 0 Participants |
| PF-07817883 100mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Pulse rate; value > 120 (bpm) | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Pulse rate; value < 40 (bpm) | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; value <50 (mmHg) | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; change >= 20 (mmHg) increase | 1 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; value < 90 (mmHg) | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Pulse rate; value > 120 (bpm) | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; change >= 30 (mmHg) increase | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; change >= 20 (mmHg) decrease | 0 Participants |
| PF-07817883 300mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; change >= 30 (mmHg) decrease | 2 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; change >= 20 (mmHg) increase | 1 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; change >= 20 (mmHg) decrease | 2 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; value < 90 (mmHg) | 1 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Pulse rate; value < 40 (bpm) | 0 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; change >= 30 (mmHg) increase | 1 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Pulse rate; value > 120 (bpm) | 0 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; change >= 30 (mmHg) decrease | 0 Participants |
| PF-07817883 600mg | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; value <50 (mmHg) | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; change >= 30 (mmHg) decrease | 3 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Pulse rate; value > 120 (bpm) | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; value < 90 (mmHg) | 1 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Systolic blood pressure; change >= 30 (mmHg) increase | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Pulse rate; value < 40 (bpm) | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; value <50 (mmHg) | 0 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; change >= 20 (mmHg) increase | 2 Participants |
| Placebo | Number of Participants Meeting Pre-defined Criteria of Vital Sign Abnormalities | Diastolic blood pressure; change >= 20 (mmHg) decrease | 2 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities
The following laboratory parameters were assessed according to pre-specified criteria for abnormalities: a) hematology; hemoglobin (gram per deciliter \[g/dL\]), (less than\[\<\]0.8\*lower limit of normal \[LLN\]), erythrocytes(10\^12/Liter \[L\])(\< 0.8\*LLN), lymphocytes(10\^9/L)(more than\[\>\]1.2\*upper limit of normal \[ULN\]), neutrophils(\> 1.2\*ULN and \< 0.8\*LLN), basophils(10\^9/L)(\> 1.2\*ULN) and eosinophils (10\^9/L)(\> 1.2\*ULN). b) clinical chemistry; bilirubin(mg/dL)(\> 1.5\*ULN), urea nitrogen(mg/dL)(\> 1.3\*ULN), creatinine(mg/dL)(\> 1.3\*ULN), potassium(milli equivalence per millilitre \[mEq/L\], (\< 0.9\*LLN and \> 1.1\*ULN), calcium (mg/dL)(\< 0.9\*LLN), bicarbonate(mEq/L)(\< 0.9\*LLN and \> 1.1\*ULN), glucose (mg/dL)(\> 1.5\*ULN), creatine kinase(units per litre \[U/L) (\> 2.0\* ULN), D-Dimer(nanogram per milliliter\[ng/mL\]), (\>1.5\*ULN) and c)urinalysis; bacteria (low power field \[LPF\]\>20). Number of participants with any laboratory abnormalities meeting pre-specified criteria are reported in this outcome measure.
Time frame: From start of study intervention up to 28 days after last dose of study intervention (up to 33 days).
Population: The SAS included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the intervention they actually received. Here 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-07817883 100mg | Number of Participants With Laboratory Test Abnormalities | 4 Participants |
| PF-07817883 300mg | Number of Participants With Laboratory Test Abnormalities | 4 Participants |
| PF-07817883 600mg | Number of Participants With Laboratory Test Abnormalities | 18 Participants |
| Placebo | Number of Participants With Laboratory Test Abnormalities | 13 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a study participant after administration of a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An adverse event is considered a treatment-emergent adverse event (TEAE) if the event started on or after the study medication start date and time. An SAE was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions) or resulted in congenital anomaly/birth defect or was considered an important medical event.
Time frame: From start of study intervention up to 28 days after last dose of study intervention (up to 33 days)
Population: The safety analysis set (SAS) included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the intervention they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07817883 100mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| PF-07817883 100mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 2 Participants |
| PF-07817883 300mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 5 Participants |
| PF-07817883 300mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 1 Participants |
| PF-07817883 600mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| PF-07817883 600mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 11 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | SAEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs | 9 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations
An AE was any untoward medical occurrence in a study participant after administration of a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An adverse event is considered a treatment-emergent adverse event (TEAE) if the event started on or after the study medication start date and time. Participants with an AE record indicating the AE caused permanent discontinuation from the study were reported under discontinuations from study due to TEAEs. Permanent discontinuations from study intervention due to TEAEs included those participants who had an AE record that indicated that action taken with study treatment was drug withdrawn but AE did not cause the participant to be discontinued from study.
Time frame: From start of study intervention up to 28 days after last dose of study intervention (up to 33 days)
Population: The SAS included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the intervention they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-07817883 100mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations | Discontinuations from study due to TEAEs | 0 Participants |
| PF-07817883 100mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations | Permanent discontinuations from study intervention due to TEAEs | 0 Participants |
| PF-07817883 300mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations | Permanent discontinuations from study intervention due to TEAEs | 0 Participants |
| PF-07817883 300mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations | Discontinuations from study due to TEAEs | 1 Participants |
| PF-07817883 600mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations | Discontinuations from study due to TEAEs | 0 Participants |
| PF-07817883 600mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations | Permanent discontinuations from study intervention due to TEAEs | 1 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations | Discontinuations from study due to TEAEs | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuations | Permanent discontinuations from study intervention due to TEAEs | 0 Participants |