Study in Healthy Adults Evaluating PF-07202954

A PHASE 1, 3-PART, SPONSOR OPEN STUDY OF PF-07202954 IN HEALTHY ADULTS: RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TO ASSESS SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE (IN PART 1), AND REPEATED (IN PART 2), ESCALATING, ORAL DOSES ALONG WITH CONDITIONAL PART 3 OF RANDOMIZED, OPEN-LABEL ASSESSMENT OF EFFECT OF FOOD ON PF-07202954 EXPOSURE

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 Overview

• Status: Completed
• Conditions: Liver Fibrosis; Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Placebo; Drug: PF-07202954 Single Dose; Drug: PF-07202954 Repeat Dose

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1; Single, Escalating Doses of PF-07202954 or Placebo (Cohorts 1 and 2)	Drug: Placebo; Matching Placebo; Drug: PF-07202954 Single Dose; 10, 30, 100, 300, 600, 900, 1200 milligrams (mg)
Experimental: Part 2; 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)	Drug: Placebo; Matching Placebo; Drug: PF-07202954 Repeat Dose; 10, 30, 100, 300, 600, 1200 milligrams (mg)
Experimental: Part 3; Single dose of PF-07202954 with a high-fat/high-caloric meal and a single dose following an overnight fast of ≥10 hours	Drug: PF-07202954 Single Dose; 10, 30, 100, 300, 600, 900, 1200 milligrams (mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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).	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.	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.	Up to a maximum of 12 weeks
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	AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf).	Day 1 (pre-dose, 0.5, 1, 2, 3, 4, 5, 8, 12, 16, 24, 36, 48 and 72 hours post-dose)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	AUClast was determined by linear/log trapezoidal method.	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.	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.	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		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	Area under the concentration curve from time 0 to end of dosing interval (AUCtau).	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		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.	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.	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.	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.	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).	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.	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.	Up to maximum of 6 weeks

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): May 13, 2021
• Primary Completion (Actual): September 17, 2021
• Study Completion (Actual): September 17, 2021

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 23, 2021

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: May 20, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Fibrosis; Liver Diseases; Fatty Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: C4171001; 2020-002121-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No