Study Of Single And Multiple Ascending Doses Of PF-07054894 In Healthy Adult Participants

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety, tolerability, and PK of single escalating doses and multiple escalating doses of PF-07054894.

Official Title
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A PHASE 1, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, STUDY TO ASSESS SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF SINGLE AND MULTIPLE ASCENDING ORAL DOSES OF PF-07054894 IN HEALTHY ADULT PARTICIPANTS

Conditions
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Healthy

Intervention / Treatment
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* Drug: PF-07054894
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female (of non-child bearing potential) participants must be 18 to 55 years of age, inclusive, and with BMI of 17.5 to 30.5 kg/m2; and a total body weight >50 kg (110 lb). Male and female of non-child bearing potential participants who are overtly healthy as determined by medical evaluation. Participants must be willing to avoid direct sunlight exposure or any high intensity ultraviolet light exposure, from admission to FU1 and to apply sun screen/lotion with a high sun protection factor, as appropriate. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, immunological/rheumatological, or allergic diseases. Evidence of active or latent or inadequately treated infection with Mycobacterium tuberculosis (TB), history of HIV infection, hepatitis B, or hepatitis C. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Have a history of systemic infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to Day 1. History of phototoxicity and photosensitivity.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-07054894<br>Participants will receive single or multiple ascending doses of oral PF-07054894 | Drug: PF-07054894<br>* Participants will receive oral ascending doses<br>|
| Placebo Comparator: Placebo<br>Participants will receive matching placebo | Drug: Placebo<br>* Participants will receive matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs following Single ascending dose (SAD) | Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs | Day 1 up to Day 28 (SAD) | 
| AEs following multiple ascending dose (MAD) | Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs | Day 1 up to Day 42 (MAD) | 
| Percentage of subjects with laboratory abnormalities |  | Day 1 up to Day 7 (SAD) or Day 1 up to Day 21 (MAD) | 
| Number of subjects with change from baseline in vital signs | Number of subjects with change from baseline of blood pressure, pulse rate, and oral temperature | Day 1 up to Day 7 (SAD) or Day 1 up to Day 21 (MAD) | 
| Number of subjects with change from baseline in electrocardiogram (ECG) parameters |  | Day 1 up to Day 7 (SAD) or Day 1 up to Day 21 (MAD) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma concentration (Cmax) | Maximum observed plasma concentration (Cmax) | Day 1 (SAD) or Day 1 and Day 14 (MAD) | 
| Time to reach plasma Cmax (Tmax) | Time to reach maximum observed plasma concentration (Tmax) | Day 1 (SAD) or Day 1 and Day 14 (MAD) | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) | Day 1 up to Day 3 (SAD) | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). | Day 1 up to Day 3 (SAD) | 
| Dose normalized Cmax (Cmax(dn)) | Dose normalized maximum plasma concentration (Cmax(dn)) | Day 1 (SAD) or Day 1 and Day 14 (MAD) | 
| Apparent Oral Clearance (CL/F) | Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed and a quantitative measure of the rate at which the drug is removed from the blood. | Day 1 (SAD) or Day 14 (MAD) | 
| Apparent Volume of Distribution (Vz/F) | Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. | Day 1 (SAD) or Day 14 (MAD) | 
| Single dose and Multiple Dose PK half-life (t½) | Plasma elimination half-life is the time measured for the plasma concentration to decrease by one half. | Day 1 (SAD) or Day 14 (MAD) | 
| Observed Accumulation Ratio for Cmax (Rac,Cmax) | Accumulation ratio based on maximum plasma concentration (Cmax) calculated as: Rac,Cmax = Cmax at steady state (ss) divided by Cmax at first dose. | MAD, Day 14 | 
| Observed Accumulation Ratio for AUCτau (Rac, AUCτau) | Accumulation ratio calculated as, Rac obtained from Area Under the Concentration Time Curve (AUCτau) from time 0-τau (Day 14) divided by AUC from time 0-τau (Day 1). | MAD, Day 14 | 
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCτau) | Area under the concentration curve from time 0 to end of dosing interval (AUCτau), where dosing interval is 12 hours. | Day 1 and Day 14 of MAD | 
| Minimum Observed Plasma Trough Concentration (Cmin) | Minimum plasma concentration over the dosing interval τau (12 hour) from first dose to last dose | Day 1 up to Day 14 of MAD | 
| Multiple dose PK/AUCτau (dn) | Dose normalized area under the curve over the dosing interval τau (12 hour) after the first and last dose (AUCτau (dn)) | Day 1 and Day 14 of MAD | 
| Cumulative Amount of Drug Recovered Unchanged in Urine during dosing interval (Ae,τau) | Cumulative amount of drug recovered unchanged in urine during the dosing interval, where the dosing interval is 12 hours (Ae,τau) | MAD, Day 14 | 
| Percentage of Dose Recovered Unchanged in Urine From Time 0 to the Dosing Interval τau (Ae,τau%) | Percent of dose recovered in urine as unchanged drug over the dosing interval (Ae,τau%) | MAD, Day 14 | 
| Renal Clearance (Clr) | Renal clearance calculated as cumulative amount of drug recovered unchanged in urine during the dosing interval (Ae,τau) divided by area under the plasma concentration time-curve from time zero to end of dosing interval (AUCτau), where dosing interval is 12 hours. | MAD, Day 14 |