Healthy
Conditions
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.
Interventions
DRUGPlacebo
Participants will receive matching placebo
DRUGPF-07054894
Participants will receive oral ascending doses
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
| Maximum Plasma concentration (Cmax) | Day 1 (SAD) or Day 1 and Day 14 (MAD) | Maximum observed plasma concentration (Cmax) |
| 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 |
| 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)) |
| 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. |
| 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. |
| 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) |
| 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)) |
Countries
Belgium
Outcome results
None listed