Study in Healthy Adults Evaluating PF-07202954

Study Overview
=================
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).

Official Title
-----------------
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

Conditions
-----------------
Non-Alcoholic Fatty Liver Disease, Liver Fibrosis

Intervention / Treatment
-----------------
* Drug: PF-07202954 Repeat Dose
* Drug: PF-07202954 Single Dose
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1<br>Single, Escalating Doses of PF-07202954 or Placebo (Cohorts 1 and 2) | Drug: PF-07202954 Single Dose<br>* 10, 30, 100, 300, 600, 900, 1200 milligrams (mg)<br>Drug: Placebo<br>* Matching Placebo<br>|
| Experimental: Part 2<br>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: PF-07202954 Repeat Dose<br>* 10, 30, 100, 300, 600, 1200 milligrams (mg)<br>Drug: Placebo<br>* Matching Placebo<br>|
| Experimental: Part 3<br>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<br>* 10, 30, 100, 300, 600, 900, 1200 milligrams (mg)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects reporting treatment emergent adverse events (AEs) | Part 1 and Part 2 | Baseline through follow up Day 30 | 
| Incidence of treatment emergent clinical laboratory abnormalities | Part 1 and Part 2 | Baseline through follow up Day 30 | 
| Incidence of treatment emergent vital signs | Part 1 and Part 2 | Baseline through follow up Day 30 | 
| Incidence of treatment emergent Electrocardiogram (ECG) abnormalities | Part 1 and Part 2 | Baseline through follow up Day 30 | 
| Maximum plasma concentration (C[max]) | Part 3 (if conducted) | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16 hour on Day 1, 24, 36 hour on Day 2, 48 hour on Day 3, 72 hour on Day 4 | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Part 3 (if conducted) | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16 hour on Day 1, 24, 36 hour on Day 2, 48 hour on Day 3, 72 hour on Day 4 | 
| Area under the plasma concentration time AUC[last]) | Part 3 (if conducted) | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16 hour on Day 1, 24, 36 hour on Day 2, 48 hour on Day 3, 72 hour on Day 4 | 
| Area Under the Curve from Time Zero to Extrapolated Infinite Time (AUCinf) | Part 3 (if conducted) | 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16 hour on Day 1, 24, 36 hour on Day 2, 48 hour on Day 3, 72 hour on Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Part 1 and Part 2 | Part 1 - 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16 hour on Day 1, 24, 36 hour on Day 2, 48 hour on Day 3, 72 hour on Day 4. Part 2 (Single Dose) - Day 1. Part 2 (Repeat Dose) - Day 7 and Day 14 | 
| Tmax | Part 1 and Part 2 | Part 1 - 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16 hour on Day 1, 24, 36 hour on Day 2, 48 hour on Day 3, 72 hour on Day 4. Part 2 (Single Dose) - Day 1. Part 2 (Repeat Dose) - Day 7 and Day 14 | 
| AUClast | Part 1 | Part 1 - 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16 hour on Day 1, 24, 36 hour on Day 2, 48 hour on Day 3, 72 hour on Day 4. | 
| AUCinf | Part 1 | Part 1 - 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16 hour on Day 1, 24, 36 hour on Day 2, 48 hour on Day 3, 72 hour on Day 4. | 
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) | Part 2 | Part 2 (Single Dose) - Day 1. Part 2 (Repeat Dose) - Day 7 and Day 14 | 
| Time measured for plasma concentration to decrease by one half (Terminal half-life) [t(1/2)]. | Part 1 and Part 2 | Part 1 - 0, 0.5, 1, 2, 3, 4, 5, 8, 12, 16 hour on Day 1, 24, 36 hour on Day 2, 48 hour on Day 3, 72 hour on Day 4. Part 2 (Repeat Dose) - Day 14 | 
| Amount of unchanged drug recovered in urine during dosing interval (AE[tau]) | Part 2 | Day 14 | 
| Percent of dose recovered in urine as unchanged drug over dosing interval (AE[tau%]) | Part 2 | Day 14 | 
| Renal Clearance (CLr) | Part 2 | Day 14 | 
| AEs | Part 3 (if conducted) | Baseline through follow up Day 30 | 
| Incidence of treatment emergent clinical laboratory abnormalities | Part 3 (if conducted) | Baseline through follow up Day 30 | 
| Incidence of treatment emergent vital signs | Part 3 (if conducted) | Baseline through follow up Day 30 | 
| ECG abnormalities | Part 3 (if conducted) | Baseline through follow up Day 30 |