A STUDY TO COMPARE THE PHARMACOKINETICS OF PF-06835919 IN PARTICIPANTS WITH AND WITHOUT HEPATIC IMPAIRMENT

A PHASE 1, NON-RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL-COHORT STUDY TO COMPARE THE PHARMACOKINETICS OF PF-06835919 IN ADULT PARTICIPANTS WITH VARYING DEGREES OF HEPATIC IMPAIRMENT RELATIVE TO PARTICIPANTS WITHOUT HEPATIC IMPAIRMENT

The study is proposed to characterize the effect of varying degrees of hepatic impairment on the plasma PK of PF-06835919

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment; Healthy Participants
• Intervention / Treatment: Drug: PF-06835919 25 mg

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles-capitale, Région DE
    • Brussels, Bruxelles-capitale, Région DE, Belgium, B-1070
      • Pfizer Clinical Research Unit - Brussels
• Czechia
  • Praha 7, Czechia, 170 00
    • Pharmaceutical Research Associates CZ, s.r.o.
• Slovakia
  • Bratislava, Slovakia, 83101
    • Summit Clinical Research, s.r.o.,

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Male and female participants between the ages of 18 (or the minimum country specific age of consent if >18) and 70 years, inclusive, at the Screening visit:
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• Body mass index (BMI) of 17.5 to 35.4 kg/m2; and a total body weight >50 kg (110 lb).
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent document (ICD) and in this protocol.

Exclusion Criteria:

• Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, ileal resection).

(Participants who have undergone cholecystectomy and/or appendectomy are eligible for this study as long as the surgery occurred more than 6 months prior to Screening)..

• At Screening, participants with a positive result for human immunodeficiency virus (HIV) antibodies, as assessed by sponsor identified central laboratory, with a single repeat permitted to assess eligibility, if needed.
• Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behaviour or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
• Use of prior/concomitant therapies.
• Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half lives preceding the first dose of investigational product used in this study (whichever is longer).
• Participants with known prior participation (ie, randomized and received at least 1 dose of investigational product) in a study involving PF 06835919.
• A positive urine drug test, for illicit drugs, and/or a positive breath alcohol test at Screening. However, participants who have been medially prescribed opiates/opiods or benzodiazepines and report the use of these drugs to the investigator at the screening visit will be allowed to participate.
• Male participants with partners who are currently pregnant.
• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing and until the follow-up contact.
• History of sensitivity to heparin or heparin induced thrombocytopenia, only if heparin is used to flush intravenous catheters used during serial blood collections.
• Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of the protocol.
• Investigator site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or Pfizer employees, including their family members, directly involved in the conduct of the study.

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: PF-06835919 with severe hepatic impairement; This arm includes participants with severe hepatic impairment who will receive a 25mg oral dose of PF-06835919	Drug: PF-06835919 25 mg; PF-06835919 in 25 mg oral tablet will be administered on Day 1
Experimental: PF-06835919 with moderate hepatic impairement; This arm includes participants with moderate hepatic impairment who will receive a 25mg oral dose of PF-06835919	Drug: PF-06835919 25 mg; PF-06835919 in 25 mg oral tablet will be administered on Day 1
Experimental: PF-06835919 with mild hepatic impairement; This arm includes participants with mild hepatic impairment who will receive a 25mg oral dose of PF-06835919	Drug: PF-06835919 25 mg; PF-06835919 in 25 mg oral tablet will be administered on Day 1
Experimental: PF-06835919 without hepatic impairment; This arm includes participants without hepatic impairment who will receive a 25mg oral dose of PF-06835919	Drug: PF-06835919 25 mg; PF-06835919 in 25 mg oral tablet will be administered on Day 1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	Predose, 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 36, 48 ,72, 96 ,120 hours post dose on Day 1.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	Baseline (Day 1) up to Day 6

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2020
• Primary Completion (Actual): July 9, 2021
• Study Completion (Actual): July 9, 2021

Study Registration Dates

• First Submitted: November 11, 2019
• First Submitted That Met QC Criteria: December 6, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Non-alcoholic steatohepatitis; Non-alcoholic Fatty Liver Disease
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: C1061013; HEPATIC IMPAIRMENT (Other Identifier: Alias Study Number); 2019-003480-21 (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: No
• Studies a U.S. FDA-regulated device product: No