Effect Of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of PF-06865571 In Subjects With Hepatic Impairment and in Healthy Subjects

Phase 1

Completed

• Conditions: Hepatic Impairment; Healthy Volunteers
• Interventions: Drug: PF-06865571 100 mg

• Registration Number: NCT04091061
• Lead Sponsor: Pfizer

Brief Summary

The current study is proposed to evaluate whether there is any clinically meaningful effect of hepatic impairment on the plasma PK of PF-06865571.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-09-13
• Study First Submitted QC: 2019-09-13
• Study First Posted: 2019-09-16
• Study Start: 2019-10-03
• Primary Completion: 2020-04-07
• Study Completion: 2020-04-07
• Status Verified: 2021-03
• Results First Submitted: 2021-03-18
• Results First Submitted QC: 2021-03-18
• Last Update Submitted: 2021-03-18
• Results First Posted: 2021-04-13
• Last Update Posted: 2021-04-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• 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, inclusive; and a total body weight >50 kg (110 lb), at the Screening visit; with a single repeat assessment of total body weight (and hence BMI), on a separate day permitted to assess eligibility, if needed.
• Capable of giving signed informed consent.

Exclusion Criteria

• Any condition possibly affecting drug absorption (eg, prior bariatric surgery,gastrectomy, ileal resection).
• 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 behavior 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.
• 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-06865571.
• A positive urine drug test, for illicit drugs on Day -1,
• At Screening or Day -1, a positive breath alcohol test.
• 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.
• Unwilling or unable to comply with the criteria in the Lifestyle Considerations.
• 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.

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PF-06865571 Severe Hepatic Impairment	PF-06865571 100 mg	This arm includes participants with severe hepatic impairment who will receive an oral dose of PF-06865571 100 mg on Day 1
PF-06865571 Healthy Participants	PF-06865571 100 mg	This arm includes healthy participants who will receive an oral dose of PF-06865571 100 mg on Day 1
PF-06865571 Moderate Hepatic Impairment	PF-06865571 100 mg	This arm includes participants with moderate hepatic impairment who will receive an oral dose of PF-06865571 100 mg on Day 1
PF-06865571 Mild Hepatic Impairment	PF-06865571 100 mg	This arm includes participants with mild hepatic impairment who will receive an oral dose of PF-06865571 100 mg on Day 1

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax)	For Cohort 1, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose. For Cohorts 2-4, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose.	Cmax of PF-06865571 was observed directly from data.
Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast)	For Cohort 1, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose. For Cohorts 2-4, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose.	AUClast of PF-06865571 was determined by linear/log trapezoidal method.
Area Under the Curve From Time 0 to Extrapolated Infinite Time (AUCinf)	For Cohort 1, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48 hours post dose. For Cohorts 2-4, pre-dose, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72 hours post dose.	AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 (pre-dose) to extrapolated infinite time (0-inf).

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Up to Day 32 (31 days after investigational product administration)	An adverse event (AE) was any untoward medical occurrence attributed to study drug in a participant who receives study drug. A 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. TEAEs were events following start of treatment.
Number of Participants With Clinical Laboratory Abnormalities	Up to Day 4 (3 days after investigational product administration)	The following parameters were analyzed for laboratory examination: hematology, clinical chemistry, and urinalysis. The abnormalities with at least 1 participant are presented here.
Number of Participants With Categorical Vital Signs Data	Up to Day 4 (3 days after investigational product administration)	Vital signs (systolic and diastolic blood pressure, and pulse rate) were obtained with participants after having sat calmly for at least 5 minutes.
Number of Participants With Categorical Electrocardiogram (ECG)	Up to Day 4 (3 days after investigational product administration)	QT interval corrected using Fridericia's formula (QTcF) was obtained with participants. All scheduled ECGs were performed after the participant had rested quietly for at least 10 minutes in a supine position.

Trial Locations

Locations (2)

University of Miami Division of Clinical Pharmacology; 🇺🇸 Miami, Florida, United States

Orlando Clinical Research Center; 🇺🇸 Orlando, Florida, United States