The study is proposed to characterize the effect of varying degrees of hepatic impairment on the plasma PK of PF-06835919
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
23
PF-06835919 in 25 mg oral tablet will be administered on Day 1
Pfizer Clinical Research Unit - Brussels
Brussels, Bruxelles-capitale, Région de, Belgium
Pharmaceutical Research Associates CZ, s.r.o.
Prague, Czechia
Summit Clinical Research, s.r.o.,
Bratislava, Slovakia
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUCinf) of PF-06835919
AUCinf was defined as area under the plasma concentration time curve from time 0 extrapolated to infinite time.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1.
Maximum Plasma Concentration (Cmax) of PF-06835919
Cmax was defined as maximum plasma concentration of PF-06835919 and observed directly from data.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1.
Unbound Area Under The Plasma Concentration-Time Curve From Time 0 Extrapolated To Infinite Time (AUCinf,u) of PF-06835919
AUCinf,u was defined as unbound area under the plasma concentration time curve from time 0 extrapolated to infinite time.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1.
Unbound Maximum Plasma Concentration (Cmax,u) of PF-06835919
Cmax,u was defined as unbound maximum plasma concentration.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1.
Fraction of Drug Unbound (fu) of PF-06835919
The fraction of PF-06835919 unbound in plasma (fu) was determined at approximately the expected Tmax in each participant.
Time frame: Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1.
Number of Participants Reporting Treatment-emergent Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. Treatment-emergent AE (TEAE) was defined as an AE with onset date occurring during the on-treatment period. AEs included all SAEs and non-SAEs.
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Time frame: Baseline (Day 1) up to follow-up (Day 31)
Number of Participants With Clinically Significant Change (Chg) From Baseline in Laboratory Tests
To determine if there were any clinically significant laboratory abnormalities, hematology (hemoglobin, hematocrit, erythrocytes, mean corpuscular hemoglobin, mean corpuscular volume, platelet count, lymphocytes, neutrophils, activated partial thromboplastin time, prothrombin time, prothrombin intl. normalized ratio), clinical chemistry (bilirubin, direct and indirect bilirubin, gamma glutamyl transferase, albumin, urea nitrogen, glucose) and urinalysis (glucose, protein, hemoglobin, urobilinogen, nitrite) tests were assessed. Each parameter was evaluated against commonly used and widely accepted criteria.
Time frame: Baseline (Day 1) up to Day 6
Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiograms (ECGs)
ECG endpoints (PR interval, QRS interval, QT interval and QTcF) meeting the criteria of potential clinical concern were summarized by treatment using categories as defined: 1. PR max. ≥300ms, %Chg ≥25/50%; 3. QRS max. ≥140ms,%Chg ≥50%; 3.maximum post-dose QTcF 450 - ≤480msec, 480 - ≤500msec and \>500msec, 30\<Chg≤60 and Chg\>60.
Time frame: Baseline (Day 1) up to Day 6