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

Pfizer84 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Healthy

Interventions

PF-07054894DRUG

Participants will receive oral ascending doses

PlaceboDRUG

Participants will receive matching placebo

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

Brussels Clinical Research Unit

Brussels, Bruxelles-capitale, Région de, Belgium

Outcomes

Primary Outcomes

AEs following Single ascending dose (SAD)

Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs

Time frame: 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

Time frame: Day 1 up to Day 42 (MAD)

Percentage of subjects with laboratory abnormalities

Time frame: 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

Time frame: 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

Time frame: Day 1 up to Day 7 (SAD) or Day 1 up to Day 21 (MAD)

Secondary Outcomes

Maximum Plasma concentration (Cmax)

Maximum observed plasma concentration (Cmax)

Time frame: Day 1 (SAD) or Day 1 and Day 14 (MAD)

Time to reach plasma Cmax (Tmax)

Time to reach maximum observed plasma concentration (Tmax)

Time frame: 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)

Data from ClinicalTrials.gov

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Time frame: 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 - ∞).

Time frame: Day 1 up to Day 3 (SAD)

Dose normalized Cmax (Cmax(dn))

Dose normalized maximum plasma concentration (Cmax(dn))

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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

Time frame: 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))

Time frame: 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)

Time frame: 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%)

Time frame: 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.

Time frame: MAD, Day 14