Study of PF-05221304 in Subjects With Varying Degrees of Hepatic Impairment
- Conditions
- Hepatic Impairment
- Interventions
- Drug: PF-05221304
- Registration Number
- NCT03309202
- Lead Sponsor
- Pfizer
- Brief Summary
Hepatic impairment PK study
- Detailed Description
This is a non randomized, open label, single dose, parallel cohort, multisite study to investigate the effect of varying degrees of hepatic impairment on the plasma pharmacokinetics (total and unbound) of PF-05221304 after a single oral dose administered in the fed state.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 24
Not provided
All subjects -
- Adults <18 years of age and >70 years of age
- BMI < 17.5 and > 35.4 kg/m2
- HIV positive
- Conditions that affect drug absorption
- Positive breath alcohol test
Healthy/ those without hepatic impairment -
- Known or suspected hepatic impairment
- Evidence of Hepatitis B or C
- On any chronic medications
Those with varying degrees of hepatic impairment -
- Not meeting Classification A, B, or C of hepatic impairment based on Child-Pugh Classification
- Evidence of Hepatic carcinoma or hepatorenal syndrome or limited predicted life expectancy
- Recent GI bleed
- Moderate or severe renal impairment
- Hepatic encephalopathy Grade 3 or higher
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 1_Without impairment PF-05221304 Single, 25 mg dose of PF-05221304 Cohort 4_Severe impairment PF-05221304 Single, 25 mg dose of PF-05221304 Cohort 3_Moderate impairment PF-05221304 Single, 25 mg dose of PF-05221304 Cohort 2_Mild impairment PF-05221304 Single, 25 mg dose of PF-05221304
- Primary Outcome Measures
Name Time Method Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose AUCinf was calculated by AUClast + (Clast\*/kel), where AUClast was the area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration, Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Unbound AUCinf (AUCinf,u) of PF-05221304 4 hours postdose AUCinf,u was calculated by fu\*AUCinf.
Fraction Unbound (fu) of PF-05221304 4 hours postdose fu was the fraction of PF-05221304 unbound in plasma. fu was calculated based on the post-dialysis plasma concentrations, post-dialysis buffer concentrations, collected post-dialysis plasma and post-dialysis buffer sample volume (assuming no volume shift prior to and after dialysis), and the total plasma concentrations.
Unbound Cmax (Cmax,u) of PF-05221304 4 hours postdose Cmax,u was calculated by fu\*Cmax.
Maximum Plasma Concentration (Cmax) of PF-05221304 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose Cmax was observed directly from data.
- Secondary Outcome Measures
Name Time Method Unbound CL/F (CLu/F) of PF-05221304 4 hours postdose CLu/F was calculated by fu\*CL/F.
Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose Tmax was observed directly from data as time of first occurrence.
Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose AUClast was calculated by linear/Log trapezoidal method.
Unbound AUClast ( AUClast,u) of PF-05221304 4 hours postdose AUClast,u was calculated by fu\*AUClast.
Apparent Clearance After Oral Dose (CL/F) of PF-05221304 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose CL/F was calculated by Dose/AUCinf.
Terminal Half-Life ( t½) of PF-05221304 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose t1/2 was calculated by loge(2)/kel.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Approximately 30 days An adverse event (AE) was any untoward medical occurrence in a study participant administered a product or medical device; the event did not need to have a causal relationship with the treatment or usage. A serious adverse event (SAE) was any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. AEs included both SAEs and AEs. TEAEs were AEs occurred following the start of treatment or AEs increasing in severity during treatment. Number of participants with both all-causality and treatment-related TEAEs are presented below.
Number of Participants With Clinical Significant Findings in Vital Signs 7 days Vital signs evaluation included: sitting systolic and diastolic blood pressure (BP), and sitting pulse rate. Clinically significant findings in vital signs were determined by the investigator.
Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data 7 days ECG evaluation included: PR interval, time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization (QRS interval), time between the start of the Q wave and the end of the T wave in the heart's electrical cycle (QT interval), QT interval corrected for heart rate using Fridericia's formula (QTcF interval), and heart rate. Clinically significant findings in ECG data were determined by the investigator.
Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose Vz/F was calculated by Dose/(AUCinf\*kel). kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Unbound Vz/F (Vz,u/F) of PF-05221304 4 hours postdose Vz,u/F was calculated by fu\*Vz/F.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology 7 days Hematology evaluation included: hemoglobin, hematocrit, erythrocytes, reticulocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin concentration (MCHC), erythrocyte mean corpuscular hemoglobin, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes, activated partial thromboplastin time and prothrombin time.
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry 7 days Clinical chemistry evaluation included: bilirubin, direct/indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase , alkaline phosphatase, protein, albumin, blood urea nitrogen, creatinine, urate, sodium, potassium, chloride, calcium, phosphate, bicarbonate, creatine kinase, and fasting glucose.
Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis 7 days Urinalysis evaluation included: scalar urine glucose, scalar ketones, scalar urine protein, scalar urine hemoglobin, scalar urobilinogen, scalar urine bilirubin, scalar nitrite, scalar leukocyte esterase, urine erythrocytes, urine leukocytes, hyaline casts, and scalar bacteria.
Trial Locations
- Locations (6)
Univerzitná Nemocnica Bratislava
🇸🇰Bratislava, Slovakia
Pharmaceutical Research Associates CZ, s.r.o.
🇨🇿Praha 7, Czechia
Summit Clinical Research s.r.o.
🇸🇰Bratislava, Slovakia
Nemocnice Na Bulovce
🇨🇿Praha 8, Czechia
Pfizer Clinical Research Unit
🇧🇪Brussels, Belgium
Orlando Clinical Research Center
🇺🇸Orlando, Florida, United States