This study will be the first time PF-06842874 is administered to humans. The purpose of Part A of the study is to investigate the safety, tolerability, and pharmacokinetics of PF-06842874 following administration of single oral doses as an immediate-release or modified-release formulation to healthy adult participants. Part B of this study will evaluate the relative bioavailability of a modified-release formulation of PF-06842874 for its potential use in future clinical studies. The effect of food on PF-06842874 pharmacokinetics may also be evaluated in this study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
44
Single dose administration of PF-06842874
Single dose administration of placebo
Relative bioavailability assessment of modified-release formulation
New Haven Clinical Research Unit
New Haven, Connecticut, United States
Pfizer New Haven Clinical Research Unit
New Haven, Connecticut, United States
Number of Participants With Treatment Emergent Treatment-Related Adverse Events (AEs)
Treatment-related AEs are any untoward medical occurrences attributed to study drug in a participant who received study drug.
Time frame: Baseline up to 35 days after last dose of study medication
Number of Participants With Clinical Laboratory Abnormalities
The following parameters will be analyzed for laboratory examination: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); liver function (aspartate aminotransferase, alanine aminotransferase, total bilirubin, lactate dehydrogenase, alkaline phosphatase, albumin, total protein); renal function (blood urea nitrogen, creatinine, uric acid); electrolytes (sodium, potassium, chloride, calcium, phosphate, bicarbonate); clinical chemistry (glucose, creatine kinase); immunology (CRP); urinalysis (dipstick \[urine specific gravity, decimal logarithm of reciprocal of hydrogen ion activity {pH} of urine, glucose, protein, blood, ketones, bilirubin\], microscopy \[urine RBC, WBC, urate crystals, calcium, oxalate, miscellaneous \[urine mucus and leucocytes\]).
Time frame: Baseline up to 10 days after last dose of study medication
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
The following parameters will be analyzed for examination of vital signs: systolic blood pressure, diastolic blood pressure, and pulse rate.
Time frame: 0, 1, 2, 3, 5, 8, 12, 24, and 48 hours post-dose
Number of Participants With Change From Baseline in Electrocardiogram (ECG) Findings
Measurements of heart rate, PR interval, QT interval, QTc intervals, and QRS complex
Time frame: 0, 1, 2, 3, 5, 8, 12, 24, and 48 hours post-dose
Abnormal rhythms as observed continuous cardiac monitoring
Cardiac rhythms measured by continuous cardiac telemetry
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Time frame: 0 to 8 hours post-dose
Number of Participants With Clinically-Significant Change From Baseline in Physical Examination Findings
A complete physical examination includes, at a minimum, head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, and gastrointestinal, musculoskeletal, and neurological systems. A limited physical examination includes, at a minimum, assessments of general appearance, the respiratory and cardiovascular systems, and participant-reported symptoms.
Time frame: Baseline up to 10 days after last dose of study medication
Maximum Observed Plasma Concentration (Cmax) of PF-06842874
Maximum observed plasma concentration for immediate-release and modified-release formulations of PF-06842874
Time frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose
Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (AUClast) of PF-06842874
Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration for immediate-release and modified-release formulations of PF-06842874
Time frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of PF-06842874
Area under the plasma concentration versus time curve (AUC) from time zero to extrapolated infinite time (0-inf) for immediate-release and modified-release formulations of PF-06842874. It is obtained from AUC(0-t) plus AUC (t-inf).
Time frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06842874
Time to reach maximum observed plasma concentration for immediate-release and modified-release formulations of PF-06842874
Time frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose
Plasma Half-Life (t1/2) of PF-06842874
Plasma half-life is the time measured for the plasma concentration to decrease by one half for immediate-release and modified-release formulations of PF-06842874.
Time frame: 0, 0.5, 1, 1.5, 2, 3, 5, 8, 12, 16, 24, 36, and 48 hours post-dose