Effect Of Hepatic Impairment on the Pharmacokinetics, Saf... | NCT04091061

NCT04091061

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

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

Interventions

Name	Type	Description	Arm Group Labels	Other Names
PF-06865571 100 mg	Drug	PF-06865571 in 100 mg oral tablet will be administered on Day 1	PF-06865571 Healthy Participants PF-06865571 Mild Hepatic Impairment

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)	Cmax of PF-06865571 was observed directly from data.	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.
Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast)	AUClast of PF-06865571 was determined by linear/log trapezoidal method.	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.
Area Under the Curve From Time 0 to Extrapolated Infinite Time (AUCinf)	AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 (pre-dose) to extrapolated infinite time (0-inf).	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.

Secondary Outcomes

Measure	Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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.

Eligibility Module

Eligibility Criteria

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.

Contacts/Locations Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Miami Division of Clinical Pharmacology		Miami	Florida	33136	United States
Orlando Clinical Research Center

References Module

Label	URL
To obtain contact information for a study center near you, click here.	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.
FG001	Cohort 2 (Mild Hepatic Impairment)

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 27, 2019	Mar 18, 2021

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

PF-06865571 Moderate Hepatic Impairment

PF-06865571 Severe Hepatic Impairment

Hepatic function was categorized based on Child Pugh Score.

Class A (5 to 6 points) for participants with mild hepatic impairment.

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.
BG001	Cohort 2 (Mild Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class A (5 to 6 points) for participants with mild hepatic impairment.
BG002	Cohort 3 (Moderate Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class B (7 to 9 points) for participants with moderate hepatic impairment.
BG003	Cohort 4 (Severe Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class C (10 to 15 points) for participants with severe hepatic impairment.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG0006 BG0016 BG0026 BG0036 BG00424

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00060.8± 3.92 BG00158.2± 5.15 BG00264.5± 5.32 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0004 BG0013 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0004 BG0014 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Maximum Observed Plasma Concentration (Cmax)

Cmax of PF-06865571 was observed directly from data.

All participants who received PF-06865571 and in whom at least 1 plasma concentration value was reported.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram per milliliter (ng/mL)

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.

ID	Title	Description
OG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.
OG001	Cohort 2 (Mild Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class A (5 to 6 points) for participants with mild hepatic impairment.
OG002	Cohort 3 (Moderate Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class B (7 to 9 points) for participants with moderate hepatic impairment.
OG003	Cohort 4 (Severe Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class C (10 to 15 points) for participants with severe hepatic impairment.

Units	Counts
Participants	OG0006 OG0016 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG000532.2± 153 OG001835.5± 39 OG002668.3± 35 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Ratio (%)	156.99			2-Sided	90	83.14	296.44			90% CIs for the ratios of adjusted geometric means (Test/Reference): Analysis 1: Mild Hepatic Impairment = Test, Without Hepatic Impairment = Reference.		Other	90% Confidence Intervals (CIs) for the ratios of adjusted geometric means (Test/Reference): Analysis 1: Mild Hepatic Impairment = Test, Without Hepatic Impairment = Reference

Primary

Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast)

AUClast of PF-06865571 was determined by linear/log trapezoidal method.

All participants dosed who had at least 1 of the PK parameters.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram*hour per milliliter (ng*hr/mL)

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.

ID	Title	Description
OG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.
OG001	Cohort 2 (Mild Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class A (5 to 6 points) for participants with mild hepatic impairment.
OG002	Cohort 3 (Moderate Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class B (7 to 9 points) for participants with moderate hepatic impairment.
OG003	Cohort 4 (Severe Hepatic Impairment)

Primary

Area Under the Curve From Time 0 to Extrapolated Infinite Time (AUCinf)

AUCinf = Area under the plasma concentration versus time curve (AUC) from time 0 (pre-dose) to extrapolated infinite time (0-inf).

All participants dosed who had at least 1 of the PK parameters.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

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.

ID	Title	Description
OG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.
OG001	Cohort 2 (Mild Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class A (5 to 6 points) for participants with mild hepatic impairment.
OG002	Cohort 3 (Moderate Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class B (7 to 9 points) for participants with moderate hepatic impairment.
OG003

Secondary

Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

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.

All participants who received PF-06865571.

Posted

Count of Participants

Participants

Up to Day 32 (31 days after investigational product administration)

ID	Title	Description
OG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.
OG001	Cohort 2 (Mild Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class A (5 to 6 points) for participants with mild hepatic impairment.
OG002	Cohort 3 (Moderate Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class B (7 to 9 points) for participants with moderate hepatic impairment.

Secondary

Number of Participants With Clinical Laboratory Abnormalities

The following parameters were analyzed for laboratory examination: hematology, clinical chemistry, and urinalysis. The abnormalities with at least 1 participant are presented here.

All participants who received PF-06865571.

Posted

Count of Participants

Participants

Up to Day 4 (3 days after investigational product administration)

ID	Title	Description
OG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.
OG001	Cohort 2 (Mild Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class A (5 to 6 points) for participants with mild hepatic impairment.
OG002	Cohort 3 (Moderate Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class B (7 to 9 points) for participants with moderate hepatic impairment.
OG003	Cohort 4 (Severe Hepatic Impairment)

Secondary

Number of Participants With Categorical Vital Signs Data

Vital signs (systolic and diastolic blood pressure, and pulse rate) were obtained with participants after having sat calmly for at least 5 minutes.

All participants who received PF-06865571.

Posted

Count of Participants

Participants

Up to Day 4 (3 days after investigational product administration)

ID	Title	Description
OG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.
OG001	Cohort 2 (Mild Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class A (5 to 6 points) for participants with mild hepatic impairment.
OG002	Cohort 3 (Moderate Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class B (7 to 9 points) for participants with moderate hepatic impairment.
OG003	Cohort 4 (Severe Hepatic Impairment)

Secondary

Number of Participants With Categorical Electrocardiogram (ECG)

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.

All participants who received PF-06865571.

Posted

Count of Participants

Participants

Up to Day 4 (3 days after investigational product administration)

ID	Title	Description
OG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.
OG001	Cohort 2 (Mild Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class A (5 to 6 points) for participants with mild hepatic impairment.
OG002	Cohort 3 (Moderate Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class B (7 to 9 points) for participants with moderate hepatic impairment.
OG003	Cohort 4 (Severe Hepatic Impairment)

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (At Risk)
EG000	Cohort 1 (Without Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. NA for participants without hepatic impairment.	6	6	6
EG001	Cohort 2 (Mild Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class A (5 to 6 points) for participants with mild hepatic impairment.	6	6	6
EG002	Cohort 3 (Moderate Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class B (7 to 9 points) for participants with moderate hepatic impairment.	6	6	6
EG003	Cohort 4 (Severe Hepatic Impairment)	Hepatic function was categorized based on Child Pugh Score. Class C (10 to 15 points) for participants with severe hepatic impairment.	6	6	6

ID	Term
D065626	Non-alcoholic Fatty Liver Disease

ID	Term
C000726790	ervogastat

Hepatic function was categorized based on Child Pugh Score.

Class C (10 to 15 points) for participants with severe hepatic impairment.

Hepatic function was categorized based on Child Pugh Score.

Class C (10 to 15 points) for participants with severe hepatic impairment.

Title	Measurements
	OG0000 OG0010 OG0020 OG0031

Title	Measurements
	OG0000 OG0010 OG0020 OG0031

Title	Measurements
	OG0000 OG0010 OG0020 OG0031

Title	Measurements
	OG0000 OG0010 OG0020 OG0031

Title	Measurements
	OG0000 OG0010 OG0020 OG0031

Title	Measurements
	OG0000 OG0010 OG0021 OG0030

Title	Measurements
	OG0000 OG0010 OG0021 OG0030

Title	Measurements
	OG0000 OG0010 OG0020 OG0033

Title	Measurements
	OG0000 OG0010 OG0021 OG0034

Title	Measurements
	OG0000 OG0010 OG0021 OG0034

Title	Measurements
	OG0000 OG0010 OG0020 OG0031

Title	Measurements
	OG0000 OG0010 OG0021 OG0031

Title	Measurements
	OG0000 OG0012 OG0021 OG0030

Title	Measurements
	OG0000 OG0010 OG0020 OG0031

Title	Measurements
	OG0000 OG0010 OG0021 OG0030

Title	Measurements
	OG0000 OG0010 OG0020 OG0031

Title	Measurements
	OG0002 OG0011 OG0022 OG0030

Title	Measurements
	OG0000 OG0010 OG0021 OG0032

Title	Measurements
	OG0000 OG0010 OG0021 OG0030

Title	Measurements
	OG0000 OG0010 OG0021 OG0030

Title	Measurements
	OG0000 OG0011 OG0021 OG0030

Title	Measurements
	OG0000 OG0011 OG0020 OG0030

ID	Term
D005234	Fatty Liver
D008107	Liver Diseases
D004066	Digestive System Diseases