The study is planned as a 3 part design with investigator and participant blinded (sponsor-open), placebo controlled, randomized, dose escalation in Part 1 and Part 2; and a randomized, open label design, in Part 3 (if conducted).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
12
10, 30, 100, 300, 600, 1200 milligrams (mg)
10, 30, 100, 300, 600, 900, 1200 milligrams (mg)
Matching Placebo
New Haven Clinical Research Unit
New Haven, Connecticut, United States
Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were AEs that occurred following the start of study treatment (either PF-07202954 or placebo) up to approximately 28 days after the last dose.
Time frame: From start of study treatment on Day 1 up to 28 days post last dose of study treatment (maximum up to 10 weeks)
Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1
Pre-defined criteria for laboratory abnormalities included, hematology: neutrophils/leukocytes (less than \[\<\] 0.8\* lower limit normal \[LLN\]); monocytes/leukocytes (greater than \[\>\] 1.2\* upper limit normal \[ULN\]); clinical chemistry: low density lipoprotein (LDL) (\>1.2\*ULN), creatine kinase (\>2.0\*ULN); and urinalysis: specific gravity (\<1.003); ketones, urine protein, urine hemoglobin, nitrite (greater than equal to \[\>=1\]), urine erythrocytes (\>= 20), red blood cells (RBC) casts (\>1), bacteria (\>20). Number of participants with any laboratory abnormality meeting pre-defined criteria was reported in this outcome measure.
Time frame: From start of study treatment on Day 1 up to 28 days post last dose of study treatment (maximum up to 10 weeks)
Number of Participants According to Categorization of Vital Signs Data: Part 1
Vital signs were categorized according to the following criteria for potential clinical concern: diastolic blood pressure (DBP): \<50 millimeter of mercury (mmHg), increase from baseline \>= 20mmHg; systolic blood pressure (SBP): \<90 mmHg, increase from baseline \>=30mmHg; pulse rate: \<40 beats per minute (bpm), \>120 bpm.
Time frame: From start of study treatment on Day 1 up to 28 days post last dose of study treatment (maximum up to 10 weeks)
Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1
ECG parameters were categorized according to the following criteria for potential clinical concern: PR interval aggregate (msec) \>=300, percent change \>=25/50 percent (%); QRS duration, aggregate (msec) \>=140, percent change \>= 50%; QT interval corrected by Fridericia's formula (QTcF) interval aggregate (msec): \>450 to \<=480, \> 480 to \<=500, \>500, change from baseline: \>30 to \<=60 and change \>60.
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Time frame: From start of study treatment on Day 1 up to 28 days post last dose of study treatment (maximum up to 10 weeks)
Number of Participants With TEAEs: Part 2
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: Up to a maximum of 12 weeks
Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 2
Pre-defined criteria for laboratory abnormalities included, hematology: neutrophils/leukocytes (\<0.8\* LLN); monocytes/leukocytes (\>1.2\* ULN); clinical chemistry: LDL (\>1.2\*ULN), creatine kinase (\>2.0\*ULN); and urinalysis: specific gravity (\<1.003); ketones, urine protein, urine hemoglobin, nitrite (\>=1), urine erythrocytes (\>=20), RBC casts (\>1), bacteria (\>20).
Time frame: Up to a maximum of 12 weeks
Number of Participants According to Categorization of Vital Signs Data: Part 2
Vital signs were planned to be categorized according to the following criteria for potential clinical concern: diastolic blood pressure: \<50 mmHg, increase from baseline \>=20mmHg; systolic blood pressure: \<90 mmHg, increase from baseline \>=30mmHg; pulse rate: \<40 bpm, \>120 bpm.
Time frame: Up to a maximum of 12 weeks
Number of Participants According to Categorization of ECG Data: Part 2
ECG parameters were planned to be categorized according to the following criteria for potential clinical concern: PR interval aggregate (msec) \>=300, percent change \>=25/50%; QRS duration, aggregate (msec) \>=140, percent change \>=50%; QTcF interval aggregate (msec): \>450 to \<=480, \>480 to \<=500, \>500, change from baseline: \>30 to \<=60 and change \>60.
Time frame: Up to a maximum of 12 weeks
Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 3
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Time for Cmax (Tmax) of PF-07202954: Part 3
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 3
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 3
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 1
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Time for Cmax (Tmax) of PF-07202954: Part 1
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 1
AUClast was determined by linear/log trapezoidal method.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 1
AUCinf was determined as 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. Treatment groups with same dose and administration were combined as planned.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Terminal Half-life (t1/2) of PF-07202954: Part 1
T1/2 was calculated as loge (2) divided by kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Treatment groups with same dose and administration were combined as planned.
Time frame: Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)
Maximum Observed Plasma Concentration (Cmax) of PF-07202954 on Day 1, 7 and 14: Part 2
Time frame: Day 1, 7 and 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours)
Time for Cmax (Tmax) of PF-07202954 on Day 1, 7 and 14: Part 2
Time frame: Day 1, 7 and 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours)
Area Under the Plasma Concentration-time Profile From Time 0 to Time Tau (AUCtau) of PF-07202954 on Day 1, 7 and 14: Part 2
Area under the concentration curve from time 0 to end of dosing interval (AUCtau).
Time frame: Day 1, 7 and 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours)
Terminal Half-life (t1/2) of PF-07202954 on Day 14: Part 2
Time frame: Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours)
Amount of Unchanged Drug Recovered in Urine During Dosing Interval (Aetau) of PF-07202954 on Day 14: Part 2
Aetau was defined as amount of unchanged drug recovered in urine during dosing interval.
Time frame: Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours)
Percent of Dose Recovered in Urine as Unchanged Drug Over Dosing Interval (Aetau%) on Day 14: Part 2
Aetau% was defined as percent of dose recovered in urine as unchanged drug over dosing interval.
Time frame: Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours)
Renal Clearance (CLr) of PF-07202954 on Day 14: Part 2
Renal clearance was amount of unchanged drug excreted in urine over the dosing interval divided by AUCtau.
Time frame: Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours)
Number of Participants With TEAEs: Part 3
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.
Time frame: Up to maximum of 6 weeks
Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 3
Pre-defined criteria for laboratory abnormalities included, hematology: neutrophils/leukocytes (\<0.8\* LLN); monocytes/leukocytes (\>1.2\* ULN); clinical chemistry: LDL (\>1.2\*ULN), creatine kinase (\>2.0\*ULN); and urinalysis: specific gravity (\<1.003); ketones, urine protein, urine hemoglobin, nitrite (\>=1), urine erythrocytes (\>=20), RBC casts (\>1), bacteria (\>20).
Time frame: Up to maximum of 6 weeks
Number of Participants According to Categorization of Vital Signs Data: Part 3
Vital signs were planned to be categorized according to the following criteria for potential clinical concern: diastolic blood pressure: \<50 mmHg, increase from baseline \>=20mmHg; systolic blood pressure: \<90 mmHg, increase from baseline \>=30mmHg; pulse rate: \<40 bpm, \>120 bpm.
Time frame: Up to maximum of 6 weeks
Number of Participants According to Categorization of ECG Data: Part 3
ECG parameters were planned to be categorized according to the following criteria for potential clinical concern: PR interval aggregate (msec) \>=300, percent change \>=25/50%; QRS duration, aggregate (msec) \>=140, percent change \>=50%; QTcF interval aggregate (msec): \>450 to \<=480, \>480 to \<=500, \>500, change from baseline: \>30 to \<=60 and change \>60.
Time frame: Up to maximum of 6 weeks