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

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo; Drug: PF-07054894

• Registration Number: NCT04388878
• Lead Sponsor: Pfizer

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-05-12
• Study First Submitted QC: 2020-05-12
• Study First Posted: 2020-05-14
• Study Start: 2020-07-27
• Primary Completion: 2022-06-21
• Study Completion: 2022-06-21
• Status Verified: 2022-07
• Last Update Submitted: 2022-07-10
• Last Update Posted: 2022-07-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 84

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants will receive matching placebo
PF-07054894	PF-07054894	Participants will receive single or multiple ascending doses of oral PF-07054894

Primary Outcome Measures

Name	Time	Method
AEs following Single ascending dose (SAD)	Day 1 up to Day 28 (SAD)	Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs
AEs following multiple ascending dose (MAD)	Day 1 up to Day 42 (MAD)	Frequency, severity and causal relationship of treatment emergent adverse events (TEAEs) and withdrawals due to TEAEs
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	Day 1 up to Day 7 (SAD) or Day 1 up to Day 21 (MAD)	Number of subjects with change from baseline of blood pressure, pulse rate, and oral temperature
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

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

Trial Locations

Locations (1)

Brussels Clinical Research Unit; 🇧🇪 Brussels, Bruxelles-capitale, Région DE, Belgium