Healthy
Conditions
Brief summary
This study is the first clinical study with PF-07328948. The safety, tolerability, and plasma pharmacokinetics and pharmacodynamics of PF-07328948 after administration of escalating, single, oral doses will be evaluated.
Interventions
DRUGPF-07328948
investigational drug administered orally
DRUGPlacebo
Placebo matching active drug administered orally
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Female participants of non-childbearing potential and males must be 18 to 60 years of age, inclusive, at the time of signing the Informed Consent Document (ICD). 2. Female participants of non-childbearing potential and males who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. 3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
Exclusion criteria
1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). * Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy). * History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, HBcAb, or HCVAb. Hepatitis B vaccination is allowed. 2. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. 3. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention. 4. Receipt of a COVID-19 vaccine within 7 days before screening or within 7 days before any visit in which a safety lab is planned. Vaccination with a COVID 19 vaccine that occurs greater than 7 days from either screening or any visit in which a safety lab is planned is permitted. 5. 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). 6. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. 7. Renal impairment as defined by an eGFR \<75 mL/min/1.73m2 calculated using CKD EPI SCr formulas. 8. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF \>450 ms, complete LBBB, signs of an acute or indeterminate age myocardial infarction, STT interval changes suggestive of myocardial ischemia, second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the uncorrected QT interval is \>450 ms, this interval should be rate corrected using the Fridericia method only and the resulting QTcF should be used for decision-making and reporting. 9. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary: * AST or ALT level ≥1.25× ULN; * Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ULN. 10. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit, or 3 ounces (90 mL) of wine). 11. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Day 1-8 per period, along with the 28-35 day post-final dose follow-up | Maximum increase from baseline in PR Interval, QRS Duration, and QTcF Interval was reported. |
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Day 1-8 per period, along with the 28-35 day post-final dose follow-up | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An adverse event is considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were flagged as TEAEs. The algorithm did not consider any events that started prior to the first dose date. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | Day 1-8 per period, along with the 28-35 day post-final dose follow-up | Pre-defined categorical criteria for laboratory abnormalities included: lymphocytes/Leukocytes \<0.8 x lower limit of normal (LLN) or \>1.2 x upper limit of normal (ULN); Neutrophils \<0.8 x LLN; Neutrophils/Leukocytes \<0.8 x LLN; Eosinophils/Leukocytes \>1.2 x ULN; Monocytes/Leukocytes \>1.2 x ULN; Bilirubin \>1.5 x ULN; Indirect Bilirubin \>1.5 x ULN; Ketones (Scalar) ≥1; URINE Hemoglobin (Scalar) ≥1; URINE Bilirubin (Scalar) ≥1; Leukocyte Esterase (Scalar) ≥1; and Bacteria (/HPF) \>20. |
| Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Day 1-8 per period, along with the 28-35 day post-final dose follow-up | Vital signs categorical criteria: 1) supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) \<50 mmHg; 3) supine pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (≥) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP ≥ 20 mmHg. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Day 1-8 per period, along with the 28-35 day post-final dose follow-up | ECG categorical criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) ≥300 millisecond (msec), b) ≥25% increase when baseline is \> 200 msec or ≥50% increase when baseline is less than or equal to (≤) 200 msec. 2\. QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) ≥140 msec, b) ≥50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and ≤480 msec, b) \>480 msec and ≤500 msec, c) \>500 msec, d) \>30 msec and ≤60 msec increase from baseline, e) \>60 msec increase from baseline |
| Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | Day 1-8 per period, along with the 28-35 day post-final dose follow-up | Maximum increase from baseline in ECG Mean Heart Rate was reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration Observed in Plasma (Cmax) | Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4) | Maximum observed plasma PF-07328948 concentration. Observed directly from data. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4) | Area under the plasma concentration time-curve from zero to the last measured concentration. It was determined by using linear/Log trapezoidal method. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4) | Area under the plasma concentration-time curve from time 0 extrapolated to infinite time. AUCinf = AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis, and Kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, AUClast = Area under the plasma concentration time-curve from zero to the last measured concentration. |
| Terminal Half-Life (t1/2) of PF-07328948 | Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4) | Terminal elimination half-life. t1/2 = Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log linear decline will be used in the regression. |
| Time to Achieve Cmax (Tmax) | Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4) | Observed directly from data as time of first occurrence. |
Countries
United States
Participant flow
Pre-assignment details
A total of 20 participants were enrolled, and received at least one dose of study intervention.
Participants by arm
| Arm | Count |
|---|---|
| PF-07328948 10 mg, PF-07328948 30 mg, PF-07328948 100 mg, Placebo Participants were assigned to Cohort 1 in four sequences (Sequence: PF-07328948 10 mg, 30 mg, 100 mg, placebo; Sequence: 10 mg, 30 mg, placebo, 300 mg; Sequence: 10 mg, placebo, 100 mg, 300 mg; and Sequence: placebo, 30 mg, 100 mg, 300 mg). | 3 |
| PF-07328948 10 mg, PF-07328948 30 mg, Placebo, PF-07328948 300 mg Participants were assigned to Cohort 1 in four sequences (Sequence: PF-07328948 10 mg, 30 mg, 100 mg, placebo; Sequence: 10 mg, 30 mg, placebo, 300 mg; Sequence: 10 mg, placebo, 100 mg, 300 mg; and Sequence: placebo, 30 mg, 100 mg, 300 mg). | 2 |
| PF-07328948 10 mg, Placebo, PF-07328948 100 mg, PF-07328948 300 mg Participants were assigned to Cohort 1 in four sequences (Sequence: PF-07328948 10 mg, 30 mg, 100 mg, placebo; Sequence: 10 mg, 30 mg, placebo, 300 mg; Sequence: 10 mg, placebo, 100 mg, 300 mg; and Sequence: placebo, 30 mg, 100 mg, 300 mg). | 2 |
| Placebo, PF-07328948 30 mg, PF-07328948 100 mg, PF-07328948 300 mg Participants were assigned to Cohort 1 in four sequences (Sequence: PF-07328948 10 mg, 30 mg, 100 mg, placebo; Sequence: 10 mg, 30 mg, placebo, 300 mg; Sequence: 10 mg, placebo, 100 mg, 300 mg; and Sequence: placebo, 30 mg, 100 mg, 300 mg). | 2 |
| PF-07328948 750 mg, PF-07328948 F mg, PF-07328948 G mg, Placebo Participants assigned to sentinel dose in Cohort 2 Period 1 were terminated after Period 1. (The letters 'F', 'G' and 'H' stand for the planned escalating doses.) | 1 |
| Placebo, PF-07328948 F mg, PF-07328948 G mg, PF-07328948 H mg Participants assigned to sentinel dose in Cohort 2 Period 1 were terminated after Period 1. (The letters 'F', 'G' and 'H' stand for the planned escalating doses.) | 1 |
| PF-07328948 300 mg, PF-07328948 750 mg, PF-07328948 1500 mg, PF-07328948 750 mg (Fed) Participants were assigned to Cohort 3 in four sequences (Sequence: 300 mg, 750 mg, 1500 mg, 750 mg \[fed\]; Sequence: 300 mg, 750 mg, placebo, 750 mg \[fed\]; Sequence: 300 mg, placebo, 1500 mg, placebo \[fed\]; and Sequence: placebo, 750 mg, 1500 mg, 750 mg \[fed\]). | 2 |
| PF-07328948 300 mg, PF-07328948 750 mg, Placebo, PF-07328948 750 mg (Fed) Participants were assigned to Cohort 3 in four sequences (Sequence: 300 mg, 750 mg, 1500 mg, 750 mg \[fed\]; Sequence: 300 mg, 750 mg, placebo, 750 mg \[fed\]; Sequence: 300 mg, placebo, 1500 mg, placebo \[fed\]; and Sequence: placebo, 750 mg, 1500 mg, 750 mg \[fed\]). | 3 |
| PF-07328948 300 mg, Placebo, PF-07328948 1500 mg, Placebo (Fed) Participants were assigned to Cohort 3 in four sequences (Sequence: 300 mg, 750 mg, 1500 mg, 750 mg \[fed\]; Sequence: 300 mg, 750 mg, placebo, 750 mg \[fed\]; Sequence: 300 mg, placebo, 1500 mg, placebo \[fed\]; and Sequence: placebo, 750 mg, 1500 mg, 750 mg \[fed\]). | 2 |
| Placebo, PF-07328948 750 mg, PF-07328948 1500 mg, PF-07328948 750 mg (Fed) Participants were assigned to Cohort 3 in four sequences (Sequence: 300 mg, 750 mg, 1500 mg, 750 mg \[fed\]; Sequence: 300 mg, 750 mg, placebo, 750 mg \[fed\]; Sequence: 300 mg, placebo, 1500 mg, placebo \[fed\]; and Sequence: placebo, 750 mg, 1500 mg, 750 mg \[fed\]). | 2 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | PF-07328948 10 mg, PF-07328948 30 mg, Placebo, PF-07328948 300 mg | PF-07328948 10 mg, Placebo, PF-07328948 100 mg, PF-07328948 300 mg | Placebo, PF-07328948 30 mg, PF-07328948 100 mg, PF-07328948 300 mg | PF-07328948 750 mg, PF-07328948 F mg, PF-07328948 G mg, Placebo | Placebo, PF-07328948 F mg, PF-07328948 G mg, PF-07328948 H mg | PF-07328948 300 mg, PF-07328948 750 mg, PF-07328948 1500 mg, PF-07328948 750 mg (Fed) | PF-07328948 10 mg, PF-07328948 30 mg, PF-07328948 100 mg, Placebo | PF-07328948 300 mg, PF-07328948 750 mg, Placebo, PF-07328948 750 mg (Fed) | PF-07328948 300 mg, Placebo, PF-07328948 1500 mg, Placebo (Fed) | Placebo, PF-07328948 750 mg, PF-07328948 1500 mg, PF-07328948 750 mg (Fed) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Customized 18-44 years | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 13 Participants |
| Age, Customized 45-60 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 3 Participants | 1 Participants | 2 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 9 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 0 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 2 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 12 | 0 / 7 | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 3 / 13 | 1 / 2 | 3 / 6 | 2 / 5 | 1 / 5 | 5 / 12 | 3 / 7 | 1 / 5 | 2 / 6 |
| serious Total, serious adverse events | 1 / 13 | 0 / 2 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 12 | 0 / 7 | 0 / 5 | 0 / 6 |
Outcome results
Primary
Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval)
Maximum increase from baseline in PR Interval, QRS Duration, and QTcF Interval was reported.
Time frame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QTcF Interval (msec) | 6.95 msec | Standard Deviation 5.949 |
| Placebo | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in PR Interval (msec) | 5.15 msec | Standard Deviation 5.536 |
| Placebo | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QRS Duration (msec) | 3.54 msec | Standard Deviation 3.227 |
| Placebo (Fed) | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QRS Duration (msec) | 10.60 msec | Standard Deviation 3.111 |
| Placebo (Fed) | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in PR Interval (msec) | 5.10 msec | Standard Deviation 1.414 |
| Placebo (Fed) | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QTcF Interval (msec) | 7.40 msec | Standard Deviation 3.96 |
| PF-07328948 10 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in PR Interval (msec) | 2.30 msec | Standard Deviation 4.26 |
| PF-07328948 10 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QRS Duration (msec) | 1.73 msec | Standard Deviation 2.534 |
| PF-07328948 10 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QTcF Interval (msec) | 3.10 msec | Standard Deviation 4.9 |
| PF-07328948 30 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QRS Duration (msec) | 2.44 msec | Standard Deviation 2.014 |
| PF-07328948 30 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in PR Interval (msec) | 2.12 msec | Standard Deviation 2.139 |
| PF-07328948 30 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QTcF Interval (msec) | 3.40 msec | Standard Deviation 2.879 |
| PF-07328948 100 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QTcF Interval (msec) | 1.78 msec | Standard Deviation 6.634 |
| PF-07328948 100 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in PR Interval (msec) | 0.80 msec | Standard Deviation 4.54 |
| PF-07328948 100 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QRS Duration (msec) | 0.14 msec | Standard Deviation 0.969 |
| PF-07328948 300 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QTcF Interval (msec) | 2.84 msec | Standard Deviation 4.702 |
| PF-07328948 300 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QRS Duration (msec) | 4.11 msec | Standard Deviation 2.858 |
| PF-07328948 300 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in PR Interval (msec) | 3.93 msec | Standard Deviation 3.215 |
| PF-07328948 750 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QTcF Interval (msec) | 6.90 msec | Standard Deviation 11.844 |
| PF-07328948 750 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QRS Duration (msec) | 0.91 msec | Standard Deviation 3.065 |
| PF-07328948 750 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in PR Interval (msec) | 6.86 msec | Standard Deviation 8.703 |
| PF-07328948 750 mg (Fed) | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in PR Interval (msec) | 10.00 msec | Standard Deviation 5.477 |
| PF-07328948 750 mg (Fed) | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QRS Duration (msec) | 6.20 msec | Standard Deviation 3.251 |
| PF-07328948 750 mg (Fed) | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QTcF Interval (msec) | 1.50 msec | Standard Deviation 5.236 |
| PF-07328948 1500 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QRS Duration (msec) | 4.40 msec | Standard Deviation 5.303 |
| PF-07328948 1500 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in PR Interval (msec) | 5.73 msec | Standard Deviation 1.952 |
| PF-07328948 1500 mg | Change From Baseline in ECG Parameters (PR Interval, QRS Duration, and QTcF Interval) | Maximum increase from baseline in QTcF Interval (msec) | 8.47 msec | Standard Deviation 8.281 |
Primary
Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate)
Maximum increase from baseline in ECG Mean Heart Rate was reported.
Time frame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | 9.52 bpm | Standard Deviation 5.179 |
| Placebo (Fed) | Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | 12.45 bpm | Standard Deviation 2.616 |
| PF-07328948 10 mg | Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | 9.75 bpm | Standard Deviation 2.752 |
| PF-07328948 30 mg | Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | 12.88 bpm | Standard Deviation 3.321 |
| PF-07328948 100 mg | Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | 8.36 bpm | Standard Deviation 4.821 |
| PF-07328948 300 mg | Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | 16.32 bpm | Standard Deviation 14.132 |
| PF-07328948 750 mg | Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | 15.53 bpm | Standard Deviation 3.892 |
| PF-07328948 750 mg (Fed) | Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | 16.32 bpm | Standard Deviation 4.437 |
| PF-07328948 1500 mg | Change From Baseline in Electrocardiogram (ECG) Parameters (ECG Mean Heart Rate) | 13.42 bpm | Standard Deviation 3.845 |
Primary
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An adverse event is considered a TEAE if the event started during the effective duration of treatment. All events that started on or after the first dosing day and time/start time, if collected, but before the end of the study were flagged as TEAEs. The algorithm did not consider any events that started prior to the first dose date. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time frame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 1 Participants |
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 1 Participants |
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 3 Participants |
| Placebo | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 1 Participants |
| Placebo (Fed) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| Placebo (Fed) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| Placebo (Fed) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| Placebo (Fed) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 1 Participants |
| PF-07328948 10 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| PF-07328948 10 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 3 Participants |
| PF-07328948 10 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| PF-07328948 10 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| PF-07328948 30 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| PF-07328948 30 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| PF-07328948 30 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 2 Participants |
| PF-07328948 30 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| PF-07328948 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 1 Participants |
| PF-07328948 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| PF-07328948 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| PF-07328948 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| PF-07328948 300 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 4 Participants |
| PF-07328948 300 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 5 Participants |
| PF-07328948 300 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| PF-07328948 300 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| PF-07328948 750 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 2 Participants |
| PF-07328948 750 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 3 Participants |
| PF-07328948 750 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| PF-07328948 750 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 1 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| PF-07328948 1500 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 1 Participants |
| PF-07328948 1500 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| PF-07328948 1500 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 2 Participants |
| PF-07328948 1500 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria
ECG categorical criteria: 1. PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): a) ≥300 millisecond (msec), b) ≥25% increase when baseline is \> 200 msec or ≥50% increase when baseline is less than or equal to (≤) 200 msec. 2\. QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): a) ≥140 msec, b) ≥50% increase from baseline. 3\. QTcF interval (QT corrected using the Fridericia formula): a) \>450 msec and ≤480 msec, b) \>480 msec and ≤500 msec, c) \>500 msec, d) \>30 msec and ≤60 msec increase from baseline, e) \>60 msec increase from baseline
Time frame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >500 msec | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >60 msec | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >480 and ≤500 msec | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | PR interval ≥300 msec | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >450 and ≤480 msec | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in PR interval ≥25/50% increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in QRS interval ≥50% increase | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| Placebo | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QRS interval ≥140 msec | 0 Participants |
| Placebo (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| Placebo (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in PR interval ≥25/50% increase | 0 Participants |
| Placebo (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >500 msec | 0 Participants |
| Placebo (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >450 and ≤480 msec | 0 Participants |
| Placebo (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >60 msec | 0 Participants |
| Placebo (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | PR interval ≥300 msec | 0 Participants |
| Placebo (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in QRS interval ≥50% increase | 0 Participants |
| Placebo (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >480 and ≤500 msec | 0 Participants |
| Placebo (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QRS interval ≥140 msec | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >450 and ≤480 msec | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in QRS interval ≥50% increase | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >60 msec | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in PR interval ≥25/50% increase | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | PR interval ≥300 msec | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >500 msec | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QRS interval ≥140 msec | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >480 and ≤500 msec | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >500 msec | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >60 msec | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QRS interval ≥140 msec | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >450 and ≤480 msec | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in QRS interval ≥50% increase | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | PR interval ≥300 msec | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in PR interval ≥25/50% increase | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >480 and ≤500 msec | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in QRS interval ≥50% increase | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | PR interval ≥300 msec | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in PR interval ≥25/50% increase | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QRS interval ≥140 msec | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >450 and ≤480 msec | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >480 and ≤500 msec | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >500 msec | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >60 msec | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | PR interval ≥300 msec | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >500 msec | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in QRS interval ≥50% increase | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QRS interval ≥140 msec | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >60 msec | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >480 and ≤500 msec | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >450 and ≤480 msec | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in PR interval ≥25/50% increase | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in QRS interval ≥50% increase | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >480 and ≤500 msec | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >500 msec | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in PR interval ≥25/50% increase | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >60 msec | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | PR interval ≥300 msec | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >450 and ≤480 msec | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QRS interval ≥140 msec | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | PR interval ≥300 msec | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >450 and ≤480 msec | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QRS interval ≥140 msec | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >480 and ≤500 msec | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in PR interval ≥25/50% increase | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >60 msec | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >500 msec | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in QRS interval ≥50% increase | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >30 and ≤60 msec | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | PR interval ≥300 msec | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >480 and ≤500 msec | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in PR interval ≥25/50% increase | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >450 and ≤480 msec | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | Change in QTcF interval >60 msec | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QRS interval ≥140 msec | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | QTcF interval >500 msec | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | %Change in QRS interval ≥50% increase | 0 Participants |
Primary
Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality
Pre-defined categorical criteria for laboratory abnormalities included: lymphocytes/Leukocytes \<0.8 x lower limit of normal (LLN) or \>1.2 x upper limit of normal (ULN); Neutrophils \<0.8 x LLN; Neutrophils/Leukocytes \<0.8 x LLN; Eosinophils/Leukocytes \>1.2 x ULN; Monocytes/Leukocytes \>1.2 x ULN; Bilirubin \>1.5 x ULN; Indirect Bilirubin \>1.5 x ULN; Ketones (Scalar) ≥1; URINE Hemoglobin (Scalar) ≥1; URINE Bilirubin (Scalar) ≥1; Leukocyte Esterase (Scalar) ≥1; and Bacteria (/HPF) \>20.
Time frame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 0 Participants |
| Placebo (Fed) | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 1 Participants |
| PF-07328948 30 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 2 Participants |
| PF-07328948 100 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 1 Participants |
| PF-07328948 300 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 3 Participants |
| PF-07328948 750 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 3 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 1 Participants |
| PF-07328948 1500 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 2 Participants |
Primary
Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria
Vital signs categorical criteria: 1) supine systolic blood pressure (SBP) \<90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) \<50 mmHg; 3) supine pulse rate \<40 or \>120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine SBP greater than or equal to (≥) 30 mmHg; 5) change from baseline (increase or decrease) in supine DBP ≥ 20 mmHg.
Time frame: Day 1-8 per period, along with the 28-35 day post-final dose follow-up
Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. Participants were analyzed according to the study intervention they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 1 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| Placebo | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| Placebo (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| Placebo (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| Placebo (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| Placebo (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| Placebo (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| Placebo (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| Placebo (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| Placebo (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| PF-07328948 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| PF-07328948 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| PF-07328948 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 1 Participants |
| PF-07328948 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 1 Participants |
| PF-07328948 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 1 Participants |
| PF-07328948 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| PF-07328948 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| PF-07328948 750 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 1 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| PF-07328948 750 mg (Fed) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| PF-07328948 1500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf)
Area under the plasma concentration-time curve from time 0 extrapolated to infinite time. AUCinf = AUClast + (Clast\*/kel), where Clast\* is the predicted plasma concentration at the last quantifiable timepoint estimated from the log-linear regression analysis, and Kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve, AUClast = Area under the plasma concentration time-curve from zero to the last measured concentration.
Time frame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
Population: All participants randomly assigned to study intervention and who received at least 1 dose of study intervention and had at least 1 of the PK parameters of interest calculated. Number of participants analyzed = participants who were evaluable for this OM and contributed to the summary statistics of this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-07328948 10 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 39050 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 19 |
| PF-07328948 30 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 114300 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
| PF-07328948 100 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 378000 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
| PF-07328948 300 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 427600 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| PF-07328948 750 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 774600 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast)
Area under the plasma concentration time-curve from zero to the last measured concentration. It was determined by using linear/Log trapezoidal method.
Time frame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
Population: All participants randomly assigned to study intervention and who received at least 1 dose of study intervention and had at least 1 of the PK parameters of interest calculated. Number of participants analyzed = participants who were evaluable for this OM and contributed to the summary statistics of this OM.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 0.0000 nanogram*hour per milliliter (ng*hr/mL) | — |
| Placebo (Fed) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 4396 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 11 |
| PF-07328948 10 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 35030 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
| PF-07328948 30 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 110200 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
| PF-07328948 100 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 363600 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
| PF-07328948 300 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 409300 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 26 |
| PF-07328948 750 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 742700 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
Secondary
Maximum Concentration Observed in Plasma (Cmax)
Maximum observed plasma PF-07328948 concentration. Observed directly from data.
Time frame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
Population: All participants randomly assigned to study intervention and who received at least 1 dose of study intervention and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Maximum Concentration Observed in Plasma (Cmax) | 294.7 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 111 |
| Placebo (Fed) | Maximum Concentration Observed in Plasma (Cmax) | 1549 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 11 |
| PF-07328948 10 mg | Maximum Concentration Observed in Plasma (Cmax) | 7049 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| PF-07328948 30 mg | Maximum Concentration Observed in Plasma (Cmax) | 19100 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| PF-07328948 100 mg | Maximum Concentration Observed in Plasma (Cmax) | 40220 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| PF-07328948 300 mg | Maximum Concentration Observed in Plasma (Cmax) | 37440 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 13 |
| PF-07328948 750 mg | Maximum Concentration Observed in Plasma (Cmax) | 61030 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
Secondary
Terminal Half-Life (t1/2) of PF-07328948
Terminal elimination half-life. t1/2 = Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log linear decline will be used in the regression.
Time frame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
Population: All participants randomly assigned to study intervention and who received at least 1 dose of study intervention and had at least 1 of the PK parameters of interest calculated. Number of participants analyzed = participants who were evaluable for this OM and contributed to the summary statistics of this OM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-07328948 10 mg | Terminal Half-Life (t1/2) of PF-07328948 | 11.58 hours (hr) | Standard Deviation 4.2565 |
| PF-07328948 30 mg | Terminal Half-Life (t1/2) of PF-07328948 | 9.941 hours (hr) | Standard Deviation 2.498 |
| PF-07328948 100 mg | Terminal Half-Life (t1/2) of PF-07328948 | 16.13 hours (hr) | Standard Deviation 6.5277 |
| PF-07328948 300 mg | Terminal Half-Life (t1/2) of PF-07328948 | 16.90 hours (hr) | Standard Deviation 5.1749 |
| PF-07328948 750 mg | Terminal Half-Life (t1/2) of PF-07328948 | 15.90 hours (hr) | Standard Deviation 5.5106 |
Secondary
Time to Achieve Cmax (Tmax)
Observed directly from data as time of first occurrence.
Time frame: Pre-dose (0 hours) and 0.5 hours, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours and 12 hours post Day 1 dosing of each Period (Periods 1-4)
Population: All participants randomly assigned to study intervention and who received at least 1 dose of study intervention and had at least 1 of the PK parameters of interest calculated.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo | Time to Achieve Cmax (Tmax) | 1.10 hours (hr) |
| Placebo (Fed) | Time to Achieve Cmax (Tmax) | 3.00 hours (hr) |
| PF-07328948 10 mg | Time to Achieve Cmax (Tmax) | 2.00 hours (hr) |
| PF-07328948 30 mg | Time to Achieve Cmax (Tmax) | 3.00 hours (hr) |
| PF-07328948 100 mg | Time to Achieve Cmax (Tmax) | 3.02 hours (hr) |
| PF-07328948 300 mg | Time to Achieve Cmax (Tmax) | 4.00 hours (hr) |
| PF-07328948 750 mg | Time to Achieve Cmax (Tmax) | 3.04 hours (hr) |