A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of PF-06651600 in Subjects With Hepatic Impairment and Healthy Volunteers

Healthy Participants Clinical Trial

Official title:

A PHASE 1, NON-RANDOMIZED, OPEN LABEL, MULTIPLE DOSE STUDY TO EVALUATE THE PHARMACOKINETICS, SAFETY AND TOLERABILITY OF PF 06651600 IN SUBJECTS WITH HEPATIC IMPAIRMENT AND IN HEALTHY SUBJECTS WITH NORMAL HEPATIC FUNCTION

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04016077
• Other study ID #: B7981016
• Status: Completed
• Phase: Phase 1
• Start date: July 19, 2019
• Est. completion date: March 5, 2020

Study information

• Verified date: April 2021
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to characterize the effect of hepatic impairment on the pharmacokinetic(s) (PK) of PF-06651600 following administration of multiple once daily doses of PF-06651600. The safety and tolerability of PF-06651600 will also be evaluated in this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: March 5, 2020
• Est. primary completion date: March 5, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• 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 40 kg/m2; and a total body weight >50 kg (110 lb)

Additional Inclusion Criteria for Participants with Normal Hepatic Function:

• Healthy male or female participants

• No known or suspected hepatic disease

Additional Inclusion Criteria for Participants with Impaired Hepatic Function:

• Stable hepatic impairment, defined as no clinically significant change in disease status within the last 30 days prior to the Screening visit

• No other ongoing clinically significant abnormalities based on medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory tests except for the abnormal findings that are related to the participant's hepatic impairment.

• Satisfy the criteria for Class A or Class B of the Child-Pugh classification (mild:

Child-Pugh Scores 5-6 points, and moderate: Child Pugh Scores 7-9 points), within 28 days of investigational product administration.

Exclusion Criteria:

• Has active acute or chronic infection requiring treatment or history of systemic infection requiring hospitalization, incl. herpes zoster, herpes simplex, tuberculosis

• Infection with hepatitis B, hepatitis C or HIV

• Any condition affecting drug absorption, distribution, metabolism and excretion (eg, status post porta-caval shunt surgery, prior bariatric surgery, gastrectomy, ileal resection)

• Has malignancy, lymphoproliferative disorder, surgery or other condition not allowed per protocol

Additional Exclusion Criteria for Participants with Normal Hepatic Function:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, gynecologic or allergic disease

Additional Exclusion Criteria for Participants with Impaired Hepatic Function:

• Has encephalopathy, severe ascites and/or pleural effusion, Child-Pugh score >9 or medical conditions (like hepatorenal syndrome, gastrointestinal hemorrhage, etc.) excluded per protocol

Related Conditions & MeSH terms

• Healthy Participants
• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• PF-06651600 30 mg
PF-06651600 in 10 mg oral tablets will be administered on days 1 to 10.

Locations

Country	Name	City	State
United States	University of Miami Division of Clinical Pharmacology	Miami	Florida
United States	Orlando Clinical Research Center	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Plasma Concentration-time Profile From Time 0 to 24 Hours (AUC24) for PF-06651600	AUC24 of PF-06651600 pre and post dose.	Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10
Primary	Maximum Plasma Concentration (Cmax) for PF-06651600	Cmax is maximum observed plasma concentration.	Hour 0 (pre-dose) on Days 7, 8 and 9, and hour 0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 12, 14, 24 hours post-dose on Day 10
Secondary	Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (All Causalities and Treatment-related)	AEs with all causalities were any untoward medical occurrences in a study participant administered a product which did not necessarily had causal relationship with the treatment or usage. An SAE was an AE resulting in any of the following endpoints or deemed significant for any other reason: death; life threatening (immediate risk of death); inpatient hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; 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 are events between first dose of study drug and up to 35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.	Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Secondary	Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)	Laboratory parameters included: hematology (hemoglobin, hematocrit, erythrocytes, leukocytes, neutrophils, prothrombin time, prothrombin intl. normalized ratio), chemistry (bilirubin, direct bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, albumin, sodium, potassium, calcium, bicarbonate and glucose), urinalysis (glucose, ketones, protein, hemoglobin, urobilinogen, bilirubin and nitrite). Each parameter was evaluated against commonly used and widely accepted criteria.	Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Secondary	Number of Participants With Out of Range Vital Signs	Vital signs included supine blood pressure, pulse rate and temperature. The pre-specified out of range criterion for supine diastolic blood pressure was change from baseline equal to or over than (=) 20 millimeter of mercury (mmHg). Clinical significance of vital signs and out of range criterion were determined at the investigator's discretion.	Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)
Secondary	Number of Adverse Events Leading to Discontinuation	Adverse events result in participants discontinuations from the study drug.	Baseline (Day 0) up to 28 days after last dose of study medication (Day 39)

External Links

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