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

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

Hepatic impairment PK study

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: PF-05221304

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, B-1070
    • Pfizer Clinical Research Unit
• Czechia
  • Praha 7, Czechia, 170 00
    • Pharmaceutical Research Associates CZ, s.r.o.
  • Praha 8, Czechia, 180 81
    • Nemocnice Na Bulovce
• Slovakia
  • Bratislava, Slovakia, 83305
    • Univerzitna nemocnica Bratislava
  • Bratislava, Slovakia, 83101
    • Summit Clinical Research s.r.o.
• United States
  • Florida
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1_Without impairment; Single, 25 mg dose of PF-05221304	Drug: PF-05221304; 25 mg dose; Other Names: experimental drug
Experimental: Cohort 2_Mild impairment; Single, 25 mg dose of PF-05221304	Drug: PF-05221304; 25 mg dose; Other Names: experimental drug
Experimental: Cohort 3_Moderate impairment; Single, 25 mg dose of PF-05221304	Drug: PF-05221304; 25 mg dose; Other Names: experimental drug
Experimental: Cohort 4_Severe impairment; Single, 25 mg dose of PF-05221304	Drug: PF-05221304; 25 mg dose; Other Names: experimental drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Unbound Cmax (Cmax,u) of PF-05221304	Cmax,u was calculated by fu*Cmax.	4 hours postdose
Unbound AUCinf (AUCinf,u) of PF-05221304	AUCinf,u was calculated by fu*AUCinf.	4 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Unbound AUClast ( AUClast,u) of PF-05221304	AUClast,u was calculated by fu*AUClast.	4 hours postdose
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
Unbound CL/F (CLu/F) of PF-05221304	CLu/F was calculated by fu*CL/F.	4 hours postdose
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
Unbound Vz/F (Vz,u/F) of PF-05221304	Vz,u/F was calculated by fu*Vz/F.	4 hours postdose
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.
• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2017
• Primary Completion (Actual): June 26, 2018
• Study Completion (Actual): July 18, 2018

Study Registration Dates

• First Submitted: October 10, 2017
• First Submitted That Met QC Criteria: October 10, 2017
• First Posted (Actual): October 13, 2017

Study Record Updates

• Last Update Posted (Actual): August 8, 2019
• Last Update Submitted That Met QC Criteria: June 19, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: C1171006; 2017-003034-86 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No