Healthy Participants
Conditions
Brief summary
The purposes of this study are: * To see how the new medicine (PF-07853578) under study is tolerated. And if there are any important side effects. And, how people feel after taking single increasing amount of the medicine by mouth. * To measure the amount of study medicine in your blood after the medicine is taken by mouth. This study is seeking for participants who: * are females of 18 to 65 years old and are not able to give birth to a child. * are males of 18 to 65 years old. * have body mass index of 16 to 31 kilograms per meter squared. * have a total body weight of more than 50 kilograms (110 pounds). Participants will be randomly selected to receive either study medicine (PF-07853578) or placebo (a pill that has no medicine in it). Participants may receive up to 4 amounts of study medicine and up to 2 amounts of placebo.
Interventions
DRUGPF-07853578
PF-07853578 will be administered as oral solutions or suspensions as escalating single doses to be determined.
DRUGPlacebo
Placebo will be administered as oral solutions or suspensions as escalating single doses to be determined.
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 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Female participants of non-childbearing potential and male participants aged 18 to 65 years at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring. 2. BMI of 16 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb).
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). 2. 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, with the exception of moderate or strong cytochrome P450 3A (CYP3A) inducers or inhibitors which are prohibited within 14 days plus 5 half-lives prior to the first dose of study intervention. 3. 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). Participation in studies of other investigational products (drug or vaccine) at any time during their participation in this study. 4. Screening supine blood pressure (BP) ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants \<60 years; and ≥150/90 mm/Hg for participants ≥60 years old, following at least 5 minutes of supine rest. 5. Renal impairment as defined by an estimated glomerular filtration rate (eGFR) of \<75 mL/min/1.73m². 6. Hematuria as defined by \>1+ heme on urine dipstick. 7. Albuminuria as defined by albumin/creatine (Cr) ratio on spot urine albumin (UA) \>30 mg/g. 8. Standard 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results. 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: * Alanine aminotransferase (ALT), aspartate aminotransferase (AST), Bilirubin ≥1.05×ULN. * Total cholesterol, triglycerides, or direct LDL ≥1.25×ULN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Day 1-11 in each period, along with the 29-36 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 1-11 in each period, along with the 29-36 day post final dose follow-up | Pre-defined categorical criteria for laboratory abnormalities included: Lymphocytes \<0.8 x lower limit of normal (LLN); Basophils/Leukocytes \> 1.2 x upper limit of normal (ULN); Eosinophils/Leukocytes \>1.2 x ULN; Monocytes/Leukocytes \>1.2 x ULN; low-density lipoprotein (LDL) Direct Endpoint Measure \>1.2 x ULN; Triglycerides \>1.3 x ULN; Specific Gravity \<1.003 or \>1.030; pH \>8; Ketones ≥1; Urobilinogen (EU) ≥1; URINE Bilirubin ≥1; Leukocyte Esterase ≥1. |
| Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Day 1-11 in each period, along with the 29-36 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 1-11 in each period, along with the 29-36 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, c) ≥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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration Observed in Plasma (Cmax) | Pre-dose (0 hour) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment period (Periods 1-4) | Maximum observed plasma PF-07328948 concentration. Observed directly from data. |
| Terminal Half-Life (t1/2) | Pre-dose (0 hour) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment 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 were used in the regression. |
| Time to Achieve Cmax (Tmax) | Pre-dose (0 hour) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment period (Periods 1-4) | Observed directly from data as time of first occurrence. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | Pre-dose (0 hours) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment 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 hour) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment period (Periods 1-4) | Area under the plasma concentration-time curve from time 0 extrapolated to infinite time. AUCinf = AUClast + (Clast\*/kel), where Clast\* was 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. |
Countries
United States
Participant flow
Pre-assignment details
A total of 23 participants were enrolled, and received at least 1 dose of study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Cohort 1 included 4 sequences, each sequence of which included 4 treatment periods: Placebo Fasted-\>PF-07853578 10 mg \[10 mg\]-\>100 mg-\>500 mg; 1 mg (low dosage strength \[LDS\])-\>Placebo Fasted-\>100 mg-\>500 mg; 1 mg (LDS)-\>10 mg-\>Placebo Fasted-\>500 mg; and 1 mg (LDS)-\>10 mg-\>100 mg-\>Placebo Fasted | 8 |
| Cohort 2 Cohort 2 included 4 sequences, each sequence of which included 4 treatment periods: Placebo Fasted-\>30 mg-\>300 mg-\>300 mg Fed; 3 mg-\>Placebo Fasted-\>300 mg-\>300 mg fed; 3 mg-\>30 mg-\>Placebo Fasted-\>Placebo Fed; and 3 mg-\>30 mg-\>300 mg-\>300 mg fed | 8 |
| Cohort 3 Cohort 3 included 2 sequences, each sequence of which included 2 treatment periods: Placebo Fasted-\>Placebo Fasted; and 8 mg-\>8 mg (intermediate dosage strength \[IDS\]) | 7 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Other | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort 1 | Cohort 2 | Cohort 3 |
|---|---|---|---|---|
| Age, Customized 18-44 years | 17 Participants | 6 Participants | 5 Participants | 6 Participants |
| Age, Customized 45-64 years | 6 Participants | 2 Participants | 3 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 7 Participants | 7 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 8 Participants | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 21 Participants | 7 Participants | 7 Participants | 7 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 | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 4 | 0 / 14 | 0 / 1 |
| other Total, other adverse events | 1 / 5 | 2 / 6 | 3 / 5 | 2 / 5 | 2 / 5 | 1 / 6 | 0 / 5 | 1 / 6 | 4 / 5 | 0 / 4 | 3 / 14 | 0 / 1 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 5 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 6 | 0 / 5 | 0 / 4 | 0 / 14 | 0 / 1 |
Outcome results
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 1-11 in each period, along with the 29-36 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) |
|---|---|---|---|
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 1 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| 3 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| 3 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| 3 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 2 Participants |
| 3 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| 8 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 1 Participants |
| 8 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| 8 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 3 Participants |
| 8 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 2 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| 10 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 2 Participants |
| 10 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| 10 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 2 Participants |
| 10 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| 30 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| 30 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 1 Participants |
| 30 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| 30 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 0 Participants |
| 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| 100 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| 300 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| 300 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| 300 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 1 Participants |
| 300 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| 300 mg Fed | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| 300 mg Fed | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| 300 mg Fed | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| 300 mg Fed | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 4 Participants |
| 500 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related SAEs | 0 Participants |
| 500 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 0 Participants |
| 500 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 0 Participants |
| 500 mg | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| Placebo Fasted | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality SAEs | 0 Participants |
| Placebo Fasted | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | All-causality AEs | 3 Participants |
| Placebo Fasted | Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) | Treatment-related AEs | 1 Participants |
| Placebo Fasted | 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) | All-causality AEs | 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 SAEs | 0 Participants |
| Placebo Fed | 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, c) ≥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 1-11 in each period, along with the 29-36 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) |
|---|---|---|
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| 3 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 1 Participants |
| 8 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| 10 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| 30 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| 100 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| 300 mg Fed | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| 500 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| Placebo Fasted | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 0 Participants |
| Placebo Fed | Number of Participants With Abnormal Electrocardiogram (ECG) Meeting Pre-Defined Categorical Criteria | 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 \<0.8 x lower limit of normal (LLN); Basophils/Leukocytes \> 1.2 x upper limit of normal (ULN); Eosinophils/Leukocytes \>1.2 x ULN; Monocytes/Leukocytes \>1.2 x ULN; low-density lipoprotein (LDL) Direct Endpoint Measure \>1.2 x ULN; Triglycerides \>1.3 x ULN; Specific Gravity \<1.003 or \>1.030; pH \>8; Ketones ≥1; Urobilinogen (EU) ≥1; URINE Bilirubin ≥1; Leukocyte Esterase ≥1.
Time frame: Day 1-11 in each period, along with the 29-36 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) |
|---|---|---|
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 4 Participants |
| 3 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 5 Participants |
| 8 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 5 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 4 Participants |
| 10 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 5 Participants |
| 30 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 5 Participants |
| 100 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 4 Participants |
| 300 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 4 Participants |
| 300 mg Fed | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 2 Participants |
| 500 mg | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 1 Participants |
| Placebo Fasted | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 11 Participants |
| Placebo Fed | Number of Participants With Clinical Laboratory Abnormalities Meeting Pre-Defined Categorical Criteria Without Regard to Baseline Abnormality | 1 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 1-11 in each period, along with the 29-36 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) |
|---|---|---|---|
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| 3 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| 3 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| 3 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| 3 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| 3 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 1 Participants |
| 3 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| 3 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| 3 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| 8 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| 8 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| 8 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| 8 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| 8 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| 8 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 1 Participants |
| 8 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| 8 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| 10 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| 30 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 1 Participants |
| 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| 100 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 2 Participants |
| 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| 300 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| 300 mg Fed | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 1 Participants |
| 300 mg Fed | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| 300 mg Fed | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| 300 mg Fed | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| 300 mg Fed | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| 300 mg Fed | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| 300 mg Fed | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 1 Participants |
| 300 mg Fed | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| 500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | DBP <50 mmHg | 0 Participants |
| 500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| 500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| 500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| 500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| 500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 0 Participants |
| 500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| 500 mg | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 0 Participants |
| Placebo Fasted | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 increase | 0 Participants |
| Placebo Fasted | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in DBP ≥20 decrease | 1 Participants |
| Placebo Fasted | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg decrease | 1 Participants |
| Placebo Fasted | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | SBP <90 mmHg | 0 Participants |
| Placebo Fasted | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Change from baseline in SBP ≥30 mmHg increase | 0 Participants |
| Placebo Fasted | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate > 120 bpm | 0 Participants |
| Placebo Fasted | Number of Participants With Vital Signs Abnormalities Meeting Pre-Defined Categorical Criteria | Pulse rate < 40 bpm | 0 Participants |
| Placebo Fasted | 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 | Pulse rate < 40 bpm | 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 > 120 bpm | 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 | DBP <50 mmHg | 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 |
| 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 |
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\* was 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 hour) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment 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 |
|---|---|---|---|
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 18.29 ng*hr/mL | Geometric Coefficient of Variation 31 |
| 3 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 46.69 ng*hr/mL | Geometric Coefficient of Variation 73 |
| 8 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 111.5 ng*hr/mL | Geometric Coefficient of Variation 60 |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 114.1 ng*hr/mL | Geometric Coefficient of Variation 44 |
| 10 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 157.0 ng*hr/mL | Geometric Coefficient of Variation 33 |
| 30 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 470.6 ng*hr/mL | Geometric Coefficient of Variation 55 |
| 100 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 1876 ng*hr/mL | Geometric Coefficient of Variation 29 |
| 300 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 4649 ng*hr/mL | Geometric Coefficient of Variation 59 |
| 300 mg Fed | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 6822 ng*hr/mL | Geometric Coefficient of Variation 67 |
| 500 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to Extrapolated Infinite Time (AUCinf) | 8066 ng*hr/mL | Geometric Coefficient of Variation 27 |
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 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment 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 |
|---|---|---|---|
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 17.03 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
| 3 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 43.52 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 77 |
| 8 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 105.8 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 62 |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 111.6 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 44 |
| 10 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 153.3 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 33 |
| 30 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 462.4 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54 |
| 100 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 1825 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| 300 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 4590 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 58 |
| 300 mg Fed | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 6747 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 66 |
| 500 mg | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Measured Concentration (AUClast) | 7774 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
Secondary
Maximum Concentration Observed in Plasma (Cmax)
Maximum observed plasma PF-07328948 concentration. Observed directly from data.
Time frame: Pre-dose (0 hour) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment 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 |
|---|---|---|---|
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Maximum Concentration Observed in Plasma (Cmax) | 7.196 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 14 |
| 3 mg | Maximum Concentration Observed in Plasma (Cmax) | 7.226 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 52 |
| 8 mg | Maximum Concentration Observed in Plasma (Cmax) | 14.87 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 66 |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Maximum Concentration Observed in Plasma (Cmax) | 41.92 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| 10 mg | Maximum Concentration Observed in Plasma (Cmax) | 17.92 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| 30 mg | Maximum Concentration Observed in Plasma (Cmax) | 43.91 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 45 |
| 100 mg | Maximum Concentration Observed in Plasma (Cmax) | 119.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
| 300 mg | Maximum Concentration Observed in Plasma (Cmax) | 355.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
| 300 mg Fed | Maximum Concentration Observed in Plasma (Cmax) | 690.6 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 53 |
| 500 mg | Maximum Concentration Observed in Plasma (Cmax) | 449.2 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
Secondary
Terminal Half-Life (t1/2)
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 were used in the regression.
Time frame: Pre-dose (0 hour) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment 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 (MEAN) | Dispersion |
|---|---|---|---|
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Terminal Half-Life (t1/2) | 5.748 hours (hr) | Standard Deviation 4.1227 |
| 3 mg | Terminal Half-Life (t1/2) | 12.78 hours (hr) | Standard Deviation 3.6983 |
| 8 mg | Terminal Half-Life (t1/2) | 15.19 hours (hr) | Standard Deviation 7.1273 |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Terminal Half-Life (t1/2) | 8.692 hours (hr) | Standard Deviation 2.4278 |
| 10 mg | Terminal Half-Life (t1/2) | 11.26 hours (hr) | Standard Deviation 4.7825 |
| 30 mg | Terminal Half-Life (t1/2) | 13.15 hours (hr) | Standard Deviation 2.599 |
| 100 mg | Terminal Half-Life (t1/2) | 13.00 hours (hr) | Standard Deviation 3.8601 |
| 300 mg | Terminal Half-Life (t1/2) | 10.44 hours (hr) | Standard Deviation 2.7311 |
| 300 mg Fed | Terminal Half-Life (t1/2) | 11.28 hours (hr) | Standard Deviation 2.707 |
| 500 mg | Terminal Half-Life (t1/2) | 14.38 hours (hr) | Standard Deviation 3.0237 |
Secondary
Time to Achieve Cmax (Tmax)
Observed directly from data as time of first occurrence.
Time frame: Pre-dose (0 hour) and 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 10 hours and 12 hours post Day 1 dosing of each treatment 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) |
|---|---|---|
| PF-07853578 1 mg (1mg) (Low Dosage Strength [LDS] Solution) | Time to Achieve Cmax (Tmax) | 0.500 hours (hr) |
| 3 mg | Time to Achieve Cmax (Tmax) | 1.08 hours (hr) |
| 8 mg | Time to Achieve Cmax (Tmax) | 1.00 hours (hr) |
| 8 mg (Intermediate Dosage Strength [IDS] Solution) | Time to Achieve Cmax (Tmax) | 0.517 hours (hr) |
| 10 mg | Time to Achieve Cmax (Tmax) | 1.00 hours (hr) |
| 30 mg | Time to Achieve Cmax (Tmax) | 2.00 hours (hr) |
| 100 mg | Time to Achieve Cmax (Tmax) | 3.00 hours (hr) |
| 300 mg | Time to Achieve Cmax (Tmax) | 2.00 hours (hr) |
| 300 mg Fed | Time to Achieve Cmax (Tmax) | 4.00 hours (hr) |
| 500 mg | Time to Achieve Cmax (Tmax) | 3.02 hours (hr) |