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

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ClinicalTrials.gov Identifier: NCT03309202
Recruitment Status : Recruiting
First Posted : October 13, 2017
Last Update Posted : March 29, 2018
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
Hepatic impairment PK study

Condition or disease Intervention/treatment Phase
Hepatic Impairment Drug: PF-05221304 Phase 1

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  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
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
Actual Study Start Date : December 19, 2017
Estimated Primary Completion Date : December 17, 2018
Estimated Study Completion Date : December 17, 2018

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



Primary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) for PF-05221304 (both total and unbound) [ Time Frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose ]
    Maximum Observed Plasma Concentration (Cmax)

  2. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0- infinity)] for PF-05221304 (as permitted for both total and unbound) [ Time Frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose ]
    AUC (0-infinity)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-infinity). It is obtained from AUC (0-t) plus AUC (t-infinity).

  3. Fraction of Unbound Drug [ Time Frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose ]
    Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration


Secondary Outcome Measures :
  1. Number of Subjects experiencing an Adverse Event [ Time Frame: Screening up to 28 days after last dose of study medication ]

    Assessment by adverse event monitoring, 12 lead ECGs, telemetry, vital signs and clinical safety laboratory measurements.

    Treatment-related AE was any untoward medical occurrence attributed to study drug in a subject who received study drug. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Relatedness to Drug was assessed by the investigator (Yes/No). Subjects with multiple occurrences of an AE within a category were counted once within the category.


  2. Time to Reach Maximum Observed Concentration for PF-05221304 (as permitted) [ Time Frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose ]
    Time to Reach Maximum Observed Plasma Concentration (Tmax)

  3. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for PF-05221304 (as permitted for both total and unbound) [ Time Frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

  4. Apparent Total Body Clearance (CL/F) for PF-05221304 (as permitted for both total and unbound) [ Time Frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose ]
    Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after apparent total body clearance is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.

  5. Apparent Volume of Distribution (Vz/F) for PF-05221304 (as permitted for both total and unbound) [ Time Frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose ]
    Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

  6. Plasma Decay Half-Life (t1/2) for PF-05221304 (as permitted) [ Time Frame: 0, 1, 2, 3, 4, 5, 8, 10, 16, 24, 36, 48, 72, 96, 120, and 144 hours post dose ]
    Plasma Decay Half-Life (t1/2)



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03309202


Contacts
Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
United States, Florida
Orlando Clinical Research Center Recruiting
Orlando, Florida, United States, 32809
Belgium
Pfizer Clinical Research Unit Recruiting
Brussels, Belgium, B-1070
Czechia
Pharmaceutical Research Associates CZ, s.r.o. Recruiting
Praha 7, Czechia, 170 00
Nemocnice Na Bulovce Recruiting
Praha 8, Czechia, 180 81
Slovakia
Summit Clinical Research s.r.o. Recruiting
Bratislava, Slovakia, 83101
Univerzitná Nemocnica Bratislava Recruiting
Bratislava, Slovakia, 83305
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT03309202     History of Changes
Other Study ID Numbers: C1171006
2017-003034-86 ( EudraCT Number )
First Posted: October 13, 2017    Key Record Dates
Last Update Posted: March 29, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases