Study in Healthy Adults Evaluating PF-07202954

Phase 1

Completed

• Conditions: Non-Alcoholic Fatty Liver Disease; Liver Fibrosis
• Interventions: Drug: PF-07202954 Single Dose; Drug: PF-07202954 Repeat Dose; Drug: Placebo

• Registration Number: NCT04857437
• Lead Sponsor: Pfizer

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).

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-04-20
• Study First Submitted QC: 2021-04-20
• Study First Posted: 2021-04-23
• Study Start: 2021-05-13
• Primary Completion: 2021-09-17
• Study Completion: 2021-09-17
• Status Verified: 2021-11
• Last Update Submitted: 2021-11-11
• Last Update Posted: 2021-11-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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)

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part 1	PF-07202954 Single Dose	Single, Escalating Doses of PF-07202954 or Placebo (Cohorts 1 and 2)
Part 1	Placebo	Single, Escalating Doses of PF-07202954 or Placebo (Cohorts 1 and 2)
Part 2	PF-07202954 Repeat Dose	Repeated, Escalating Doses of PF-07202954 or placebo from Day 1 to Day 14, inclusive (Cohorts 3, 4, 5, 6 7, and optional Cohort 8)
Part 2	Placebo	Repeated, Escalating Doses of PF-07202954 or placebo from Day 1 to Day 14, inclusive (Cohorts 3, 4, 5, 6 7, and optional Cohort 8)
Part 3	PF-07202954 Single Dose	Single dose of PF-07202954 with a high-fat/high-caloric meal and a single dose following an overnight fast of ≥10 hours

Primary Outcome Measures

Name	Time	Method
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 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)
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 Outcome Measures

Name	Time	Method
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)
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.
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).
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.
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.

Trial Locations

Locations (1)

New Haven Clinical Research Unit; 🇺🇸 New Haven, Connecticut, United States