Study of PF-05221304 in Subjects With Varying Degrees of Hepatic Impairment

Hepatic Impairment Clinical Trial

Official title:

A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL COHORT STUDY TO COMPARE THE PHARMACOKINETICS OF PF-05221304 IN ADULT SUBJECTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO SUBJECTS WITHOUT HEPATIC IMPAIRMENT

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03309202
• Other study ID #: C1171006
• Secondary ID: 2017-003034-86
• Status: Completed
• Phase: Phase 1
• Start date: December 19, 2017
• Est. completion date: July 18, 2018

Study information

• Verified date: June 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Hepatic impairment PK study

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 information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 18, 2018
• Est. primary completion date: June 26, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Key Exclusion Criteria:

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

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• PF-05221304
25 mg dose

Locations

Country	Name	City	State
Belgium	Pfizer Clinical Research Unit	Brussels
Czechia	Pharmaceutical Research Associates CZ, s.r.o.	Praha 7
Czechia	Nemocnice Na Bulovce	Praha 8
Slovakia	Summit Clinical Research s.r.o.	Bratislava
Slovakia	Univerzitná Nemocnica Bratislava	Bratislava
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Belgium,  Czechia,  Slovakia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Plasma Concentration (Cmax) of PF-05221304	Cmax was observed directly from data.	0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Primary	Area Under the Plasma Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05221304	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.	0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Primary	Fraction Unbound (fu) of PF-05221304	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.	4 hours postdose
Primary	Unbound Cmax (Cmax,u) of PF-05221304	Cmax,u was calculated by fu*Cmax.	4 hours postdose
Primary	Unbound AUCinf (AUCinf,u) of PF-05221304	AUCinf,u was calculated by fu*AUCinf.	4 hours postdose
Secondary	Time to Reach Maximum Plasma Concentration (Tmax) of PF-05221304	Tmax was observed directly from data as time of first occurrence.	0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Secondary	Area Under Concentration Time Curve From Time 0 to Time of Last Quantifiable Concentration (AUClast) of PF-05221304	AUClast was calculated by linear/Log trapezoidal method.	0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Secondary	Unbound AUClast ( AUClast,u) of PF-05221304	AUClast,u was calculated by fu*AUClast.	4 hours postdose
Secondary	Apparent Clearance After Oral Dose (CL/F) of PF-05221304	CL/F was calculated by Dose/AUCinf.	0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Secondary	Unbound CL/F (CLu/F) of PF-05221304	CLu/F was calculated by fu*CL/F.	4 hours postdose
Secondary	Apparent Volume of Distribution After Oral Dose (Vz/F) of PF-05221304	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.	0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Secondary	Unbound Vz/F (Vz,u/F) of PF-05221304	Vz,u/F was calculated by fu*Vz/F.	4 hours postdose
Secondary	Terminal Half-Life ( t½) of PF-05221304	t1/2 was calculated by loge(2)/kel.	0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, 144 hours postdose
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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.	Approximately 30 days
Secondary	Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Hematology	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.	7 days
Secondary	Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Clinical Chemistry	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.	7 days
Secondary	Number of Paticipants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)-Urinalysis	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.	7 days
Secondary	Number of Participants With Clinical Significant Findings in Vital Signs	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.	7 days
Secondary	Number of Participants With Clinically Significant Findings in Electrocardiogram (ECG) Data	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.	7 days

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