Liver Fibrosis, Non-Alcoholic Fatty Liver Disease
Conditions
Brief summary
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).
Interventions
DRUGPF-07202954 Repeat Dose
10, 30, 100, 300, 600, 1200 milligrams (mg)
DRUGPF-07202954 Single Dose
10, 30, 100, 300, 600, 900, 1200 milligrams (mg)
DRUGPlacebo
Matching Placebo
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
- healthy subjects (all 3 Parts) * evidence of steatosis on FibroScan (Part 2 only) * BMI 17.5 to 30.5 kg/m2 (Part 1, Part 3) * BMI 17.5 to 35.4 kg/m2 (Part 2)
Exclusion criteria
- evidence of clinically significant disease * subjects on chronic medications * clinically significant, abnormal laboratory results, vital signs, or cardiac conduction abnormalities * contraindication to MRI (Part 2, only)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 3 | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose) | — |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1 | From start of study treatment on Day 1 up to 28 days post last dose of study treatment (maximum up to 10 weeks) | 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. |
| Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1 | From start of study treatment on Day 1 up to 28 days post last dose of study treatment (maximum up to 10 weeks) | 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. |
| Number of Participants According to Categorization of Vital Signs Data: Part 1 | From start of study treatment on Day 1 up to 28 days post last dose of study treatment (maximum up to 10 weeks) | 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. |
| Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | From start of study treatment on Day 1 up to 28 days post last dose of study treatment (maximum up to 10 weeks) | 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. |
| Number of Participants With TEAEs: Part 2 | Up to a maximum of 12 weeks | 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. |
| Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 2 | Up to a maximum of 12 weeks | 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). |
| Number of Participants According to Categorization of Vital Signs Data: Part 2 | Up to a maximum of 12 weeks | 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. |
| Number of Participants According to Categorization of ECG Data: Part 2 | Up to a maximum of 12 weeks | 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. |
| Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 3 | 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 | 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 | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose) | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With TEAEs: Part 3 | Up to maximum of 6 weeks | 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. |
| Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 3 | Up to maximum of 6 weeks | 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). |
| Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 1 | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose) | — |
| Number of Participants According to Categorization of ECG Data: Part 3 | Up to maximum of 6 weeks | 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. |
| Number of Participants According to Categorization of Vital Signs Data: Part 3 | Up to maximum of 6 weeks | 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 for Cmax (Tmax) of PF-07202954: Part 1 | 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 | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose) | AUClast was determined by linear/log trapezoidal method. |
| Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 1 | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose) | 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. |
| Terminal Half-life (t1/2) of PF-07202954: Part 1 | Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose) | 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. |
| Maximum Observed Plasma Concentration (Cmax) of PF-07202954 on Day 1, 7 and 14: Part 2 | 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 | 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 | 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 concentration curve from time 0 to end of dosing interval (AUCtau). |
| Terminal Half-life (t1/2) of PF-07202954 on Day 14: Part 2 | 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 | Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours) | Aetau was defined as amount of unchanged drug recovered in urine during dosing interval. |
| Percent of Dose Recovered in Urine as Unchanged Drug Over Dosing Interval (Aetau%) on Day 14: Part 2 | Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours) | Aetau% was defined as percent of dose recovered in urine as unchanged drug over dosing interval. |
| Renal Clearance (CLr) of PF-07202954 on Day 14: Part 2 | Day 14 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 10, 12, 14, 16 and 24 hours) | Renal clearance was amount of unchanged drug excreted in urine over the dosing interval divided by AUCtau. |
Countries
United States
Participant flow
Recruitment details
Study originally had 3 parts. Sponsor strategically decided not to conduct Part 2 and 3, based on results from Part 1 of the study. This decision was not due to any safety concern from Part 1 of the study. The study was concluded following Part 1; hence, no participants were enrolled in Part 2 and 3.
Participants by arm
| Arm | Count |
|---|---|
| Part 1 Cohort 1: All Participants All participants who were randomized to either of the four treatment sequences in Cohort 1 and received placebo and escalating doses of PF-07202954 either with std meal or with high fat/high calorie meal in Periods 1, 2, 3 or 4 were included. All doses were administered once on Day 1 of each period via the oral route. The dosing in each period was separated by an interval of at least 10 days. | 6 |
| Part 1 Cohort 2: All Participants All participants who were randomized to either of the four treatment sequences in Cohort 2 and received placebo and escalating doses of PF-07202954 with either std meal or under fasting condition in Period 1, 2, 3 or 4 were included. All doses were administered once on Day 1 of each period via the oral route. The dosing in each period was separated by an interval of at least 10 days. | 6 |
| Total | 12 |
Baseline characteristics
| Characteristic | Part 1 Cohort 1: All Participants | Part 1 Cohort 2: All Participants | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 9 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 4 | 0 / 4 | 0 / 9 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 2 |
| other Total, other adverse events | 3 / 11 | 0 / 4 | 1 / 4 | 2 / 9 | 1 / 5 | 0 / 4 | 1 / 5 | 0 / 2 |
| serious Total, serious adverse events | 0 / 11 | 0 / 4 | 0 / 4 | 0 / 9 | 0 / 5 | 0 / 4 | 0 / 5 | 0 / 2 |
Outcome results
Primary
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)
Population: Data was not collected as no participants were enrolled in Part 3 of the study.
Primary
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)
Population: Data was not collected as no participants were enrolled in Part 3 of the study.
Primary
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)
Population: Data was not collected as no participants were enrolled in Part 3 of the study.
Primary
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
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Primary
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.
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)
Population: Safety population included all participants who were randomly assigned to study treatment and who took at least 1 dose of study treatment. Treatment groups with same dose and administration were combined as planned.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >30 to <=60 | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): percent change >=50% | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >=500 | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >480 to <=500 | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): change >60 | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): percent change >=25/50% | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >450 to <=480 | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): >=140 | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): >=300 | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): >=140 | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): >=300 | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): percent change >=50% | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >30 to <=60 | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >450 to <=480 | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): change >60 | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): percent change >=25/50% | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >480 to <=500 | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >=500 | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): >=140 | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >480 to <=500 | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): change >60 | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): percent change >=25/50% | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): >=300 | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >30 to <=60 | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): percent change >=50% | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >=500 | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >450 to <=480 | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): percent change >=50% | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): >=140 | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >450 to <=480 | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >30 to <=60 | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): percent change >=25/50% | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): change >60 | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >=500 | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): >=300 | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >480 to <=500 | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >450 to <=480 | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): >=300 | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): percent change >=25/50% | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): >=140 | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): percent change >=50% | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >480 to <=500 | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >=500 | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >30 to <=60 | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): change >60 | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): percent change >=25/50% | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): >=300 | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >=500 | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): >=140 | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): percent change >=50% | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): change >60 | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >450 to <=480 | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >30 to <=60 | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >480 to <=500 | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >30 to <=60 | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): >=300 | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >450 to <=480 | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >=500 | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): percent change >=50% | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): >=140 | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): percent change >=25/50% | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): change >60 | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >480 to <=500 | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): change >60 | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >480 to <=500 | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): percent change >=50% | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QRS duration, aggregate (msec): >=140 | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >=500 | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): percent change >=25/50% | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >30 to <=60 | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | PR interval aggregate (msec): >=300 | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Electrocardiogram (ECG) Data: Part 1 | QTcF interval aggregate (msec): >450 to <=480 | 0 Participants |
Primary
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)
Population: Safety population included all participants who were randomly assigned to study treatment and who took at least 1 dose of study treatment. Treatment groups with same dose and administration were combined as planned.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: >120 bpm | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: <50 mmHg | 1 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: Increase from baseline >=20mmHg | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: <90 mmHg | 1 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: <40 bpm | 0 Participants |
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: Increase from baseline >=30 mmHg | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: <90 mmHg | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: <50 mmHg | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: Increase from baseline >=30 mmHg | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: >120 bpm | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: Increase from baseline >=20mmHg | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: <40 bpm | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: <40 bpm | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: <90 mmHg | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: Increase from baseline >=20mmHg | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: Increase from baseline >=30 mmHg | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: >120 bpm | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: <50 mmHg | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: <40 bpm | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: <50 mmHg | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: Increase from baseline >=20mmHg | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: <90 mmHg | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: Increase from baseline >=30 mmHg | 0 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: >120 bpm | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: <40 bpm | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: Increase from baseline >=20mmHg | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: >120 bpm | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: <50 mmHg | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: Increase from baseline >=30 mmHg | 0 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: <90 mmHg | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: <90 mmHg | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: Increase from baseline >=30 mmHg | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: Increase from baseline >=20mmHg | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: <40 bpm | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: <50 mmHg | 0 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: >120 bpm | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: Increase from baseline >=30 mmHg | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: <40 bpm | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: <50 mmHg | 1 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: <90 mmHg | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: >120 bpm | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: Increase from baseline >=20mmHg | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: Increase from baseline >=30 mmHg | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | SBP: <90 mmHg | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: >120 bpm | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | Pulse rate: <40 bpm | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: <50 mmHg | 0 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants According to Categorization of Vital Signs Data: Part 1 | DBP: Increase from baseline >=20mmHg | 0 Participants |
Primary
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
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Primary
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)
Population: Safety population included all participants who were randomly assigned to study treatment and who took at least 1 dose of study treatment. Treatment groups with same dose and administration were combined as planned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1 | 0 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1 | 2 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1 | 3 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1 | 6 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1 | 5 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1 | 3 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1 | 4 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants With Laboratory Abnormalities Meeting Pre-defined Criteria: Part 1 | 2 Participants |
Primary
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
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Primary
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
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Primary
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)
Population: Safety population included all participants who were randomly assigned to study treatment and who took at least 1 dose of study treatment. Treatment groups with same dose and administration were combined as planned.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 and 2: Placebo: Part 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1 | 3 Participants |
| Cohort 1: PF-07202954 10 mg: Part 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1 | 0 Participants |
| Cohort 2: PF-07202954 30 mg: Part 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1 | 1 Participants |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1 | 2 Participants |
| Cohort 2: PF-07202954 300 mg: Part 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1 | 1 Participants |
| Cohort 1: PF-07202954 600 mg: Part 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1 | 0 Participants |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1 | 1 Participants |
| Cohort 2: PF-07202954 100 mg Fasted: Part 1 | Number of Participants With Treatment Emergent Adverse Events (TEAEs): Part 1 | 0 Participants |
Primary
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)
Population: Data was not collected as no participants were enrolled in Part 3 of the study.
Secondary
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)
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Secondary
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)
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Secondary
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)
Population: PK parameter population included all participants who received at least 1 dose of PF-07202954 and who had at least 1 of the PK parameters of interest calculated in Part 1. PK data was not summarized for doses with less than 3 participants as pre-specified in the statistical analysis plan; hence, individual values were reported for 'Cohort 2: PF-07202954 100 mg Fasted: Part 1' arm. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 and 2: Placebo: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 1 | 185.6 Nanogram*hour per milliliter | Geometric Coefficient of Variation 29 |
| Cohort 1: PF-07202954 10 mg: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 1 | 410.1 Nanogram*hour per milliliter | Geometric Coefficient of Variation 14 |
| Cohort 2: PF-07202954 30 mg: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 1 | 1935 Nanogram*hour per milliliter | Geometric Coefficient of Variation 28 |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 1 | 5580 Nanogram*hour per milliliter | Geometric Coefficient of Variation 13 |
| Cohort 2: PF-07202954 300 mg: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 1 | 13980 Nanogram*hour per milliliter | Geometric Coefficient of Variation 28 |
| Cohort 1: PF-07202954 600 mg: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 1 | 1784 Nanogram*hour per milliliter | Geometric Coefficient of Variation 30 |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-07202954: Part 1 | NA Nanogram*hour per milliliter | — |
Secondary
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)
Population: PK parameter population included all participants who received at least 1 dose of PF-07202954 and who had at least 1 of the PK parameters of interest calculated in Part 1. PK data was not summarized for doses with less than 3 participants as pre-specified in the statistical analysis plan; hence, individual values were reported for 'Cohort 2: PF-07202954 100 mg Fasted: Part 1' arm. Treatment groups with same dose and administration were combined as planned.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 and 2: Placebo: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 1 | 179.9 Nanogram*hour per milliliter | Geometric Coefficient of Variation 30 |
| Cohort 1: PF-07202954 10 mg: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 1 | 402.1 Nanogram*hour per milliliter | Geometric Coefficient of Variation 14 |
| Cohort 2: PF-07202954 30 mg: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 1 | 1905 Nanogram*hour per milliliter | Geometric Coefficient of Variation 27 |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 1 | 5506 Nanogram*hour per milliliter | Geometric Coefficient of Variation 13 |
| Cohort 2: PF-07202954 300 mg: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 1 | 13850 Nanogram*hour per milliliter | Geometric Coefficient of Variation 28 |
| Cohort 1: PF-07202954 600 mg: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 1 | 1834 Nanogram*hour per milliliter | Geometric Coefficient of Variation 28 |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Area Under the Plasma Concentration Time Profile From Time Zero to the Time of Last Quantifiable Concentration (AUClast) of PF-07202954: Part 1 | NA Nanogram*hour per milliliter | — |
Secondary
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)
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Secondary
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)
Population: Pharmacokinetic (PK) parameter population included all participants who received at least 1 dose of PF-07202954 and had at least 1 of the PK parameters of interest calculated in Part 1. PK data was not summarized for doses with less than 3 participants as pre-specified in statistical analysis plan; hence, individual values were reported for 'Cohort 2: PF-07202954 100 mg Fasted: Part 1' arm. Treatment groups with same dose and administration were combined as planned.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 and 2: Placebo: Part 1 | Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 1 | 23.92 Nanogram per milliliter | Geometric Coefficient of Variation 20 |
| Cohort 1: PF-07202954 10 mg: Part 1 | Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 1 | 55.64 Nanogram per milliliter | Geometric Coefficient of Variation 28 |
| Cohort 2: PF-07202954 30 mg: Part 1 | Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 1 | 226.6 Nanogram per milliliter | Geometric Coefficient of Variation 26 |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 1 | 774.2 Nanogram per milliliter | Geometric Coefficient of Variation 27 |
| Cohort 2: PF-07202954 300 mg: Part 1 | Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 1 | 2067 Nanogram per milliliter | Geometric Coefficient of Variation 66 |
| Cohort 1: PF-07202954 600 mg: Part 1 | Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 1 | 195.7 Nanogram per milliliter | Geometric Coefficient of Variation 20 |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Maximum Observed Plasma Concentration (Cmax) of PF-07202954: Part 1 | NA Nanogram per milliliter | — |
Secondary
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
Population: Data was not collected as no participants were enrolled in Part 3 of the study.
Secondary
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
Population: Data was not collected as no participants were enrolled in Part 3 of the study.
Secondary
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
Population: Data was not collected as no participants were enrolled in Part 3 of the study.
Secondary
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
Population: Data was not collected as no participants were enrolled in Part 3 of the study.
Secondary
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)
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Secondary
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)
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Secondary
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)
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Secondary
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)
Population: PK parameter population included all participants who received at least 1 dose of PF-07202954 and who had at least 1 of the PK parameters of interest calculated in Part 1. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 and 2: Placebo: Part 1 | Terminal Half-life (t1/2) of PF-07202954: Part 1 | 5.740 Hours | Standard Deviation 1.1641 |
| Cohort 1: PF-07202954 10 mg: Part 1 | Terminal Half-life (t1/2) of PF-07202954: Part 1 | 5.615 Hours | Standard Deviation 1.6562 |
| Cohort 2: PF-07202954 30 mg: Part 1 | Terminal Half-life (t1/2) of PF-07202954: Part 1 | 11.43 Hours | Standard Deviation 5.8788 |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Terminal Half-life (t1/2) of PF-07202954: Part 1 | 10.55 Hours | Standard Deviation 3.9217 |
| Cohort 2: PF-07202954 300 mg: Part 1 | Terminal Half-life (t1/2) of PF-07202954: Part 1 | 14.81 Hours | Standard Deviation 6.7702 |
| Cohort 1: PF-07202954 600 mg: Part 1 | Terminal Half-life (t1/2) of PF-07202954: Part 1 | 15.85 Hours | Standard Deviation 1.9209 |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Terminal Half-life (t1/2) of PF-07202954: Part 1 | NA Hours | — |
Secondary
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)
Population: Data was not collected as no participants were enrolled in Part 2 of the study.
Secondary
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)
Population: PK parameter population included all participants who received at least 1 dose of PF-07202954 and who had at least 1 of the PK parameters of interest calculated in Part 1. Treatment groups with same dose and administration were combined as planned.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1 and 2: Placebo: Part 1 | Time for Cmax (Tmax) of PF-07202954: Part 1 | 1.500 Hours |
| Cohort 1: PF-07202954 10 mg: Part 1 | Time for Cmax (Tmax) of PF-07202954: Part 1 | 0.7500 Hours |
| Cohort 2: PF-07202954 30 mg: Part 1 | Time for Cmax (Tmax) of PF-07202954: Part 1 | 3.000 Hours |
| Cohort 1 and 2: PF-07202954 100 mg Standard Meal: Part 1 | Time for Cmax (Tmax) of PF-07202954: Part 1 | 1.000 Hours |
| Cohort 2: PF-07202954 300 mg: Part 1 | Time for Cmax (Tmax) of PF-07202954: Part 1 | 1.750 Hours |
| Cohort 1: PF-07202954 600 mg: Part 1 | Time for Cmax (Tmax) of PF-07202954: Part 1 | 3.000 Hours |
| Cohort 1: PF-07202954 100 mg High Fat / High Calorie Meal: Part 1 | Time for Cmax (Tmax) of PF-07202954: Part 1 | NA Hours |