2-Week Study In People With Nonalcoholic Fatty Liver Disease

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Placebo

PF-06865571

About this trial

This is an interventional basic science trial for Non-alcoholic Steatohepatitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

controlled attenuation parameter greater than or equal to 260 dB/m via FibroScan
liver fat greater than or equal to 6% via MRI

Exclusion Criteria:

Chronic liver disease
Type 2 diabetes requiring drug treatment
Unable to undergo MRI
History of heart attack or stroke

Sites / Locations

Anaheim Clinical Trials, LLC
New Haven Clinical Research Unit
Qps-Mra, Llc
PPD Development, LP
High Point Clinical Trials Center
Clinical Trials of Texas, Inc.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

PF-06865571 100 mg

PF-06865571 600 mg

Arm Description

Outcomes

Primary Outcome Measures

Relative Change From Baseline in Whole Liver Fat at Day 15 as Assessed by Magnetic Resonance Imaging (MRI) - Proton Density Fat Fraction (PDFF)

MRI-PDFF is an established method that enables quantification of fat content in the liver. The value of whole liver fat as assessed by MRI-PDFF is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level.

Secondary Outcome Measures

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs.

Number of Participants With Laboratory Test Abnormalities

Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes); chemistry (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, sodium, potassium, calcium, chloride, bicarbonate); urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, urine erythrocytes, urine leukocytes, hyaline casts); biomarker (total cholesterol, low-density and high-density lipoprotein cholesterol, triglycerides, fasting glucose). Participants with any of the laboratory test abnormalities were counted.

Number of Participants With Vital Sign Abnormalities

Vital sign categorical summarization criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine DBP greater than or equal to (>=) 20 mmHg; 5) change from baseline (increase or decrease) in supine SBP >=30 mmHg.

Number of Participants With Electrocardiogram (ECG) Abnormalities

ECG categorical summarization criteria: 1) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): >=140 milliseconds (msec), >=50% change from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): >=300 msec, >=25% change when baseline is > 200 msec or >=50% change when baseline is less than or equal to (<=) 200 msec; 3) QTcF interval (heart rate corrected QT [time between the start of the ECG Q wave and the end of the T wave in the heart's electrical cycle] using Fridericia's formula): absolute value of >450 to 480 msec, >480 to 500 msec, >500 msec; a change from baseline of >30 to 60 msec or >60 msec.

Maximum Plasma Concentration (Cmax) For PF-06865571

Cmax of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages.

Area Under the Plasma Concentration-Time Profile Over the Dosing Interval (AUCtau) For PF-06865571

AUCtau of PF-06865571 on Day 14 was obtained by linear/log trapezoidal method. The dosing interval (tau) was 12 hours. Geometric coefficients of variations were reported as percentages.

Time to Reach Maximum Plasma Concentration (Tmax) For PF-06865571

Tmax of PF-06865571 on Day 14 was observed directly from data as time of Cmax occurrence.

Minimum Plasma Concentration (Cmin) For PF-06865571

Cmin of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages.

Apparent Oral Clearance (CL/F) For PF-06865571

CL/F of PF-06865571 on Day 14 was calculated as Dose/AUCtau. Geometric coefficients of variations were reported as percentages.

Peak-to-Trough Ratio (PTR) For PF-06865571

PTR of PF-06865571 on Day 14 was calculated as Cmax/Cmin. Geometric coefficients of variations were reported as percentages.

Full Information

NCT ID

NCT03513588

First Posted

April 19, 2018

Last Updated

February 28, 2020

Sponsor

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT03513588

Brief Title

2-Week Study In People With Nonalcoholic Fatty Liver Disease

Official Title

A PHASE 1B, RANDOMIZED, DOUBLE-BLIND (SPONSOR-OPEN), PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACODYNAMICS AND PHARMACOKINETICS OF MULTIPLE ORAL DOSES OF PF- 06865571 FOR 2 WEEKS IN ADULTS WITH NONALCOHOLIC FATTY LIVER DISEASE

Study Type

Interventional

2. Study Status

Record Verification Date

February 2020

Overall Recruitment Status

Completed

Study Start Date

June 21, 2018 (Actual)

Primary Completion Date

March 8, 2019 (Actual)

Study Completion Date

April 4, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Data Monitoring Committee

No

5. Study Description

Brief Summary

2-week study in people with nonalcoholic fatty liver disease. Study drug at 1 of 2 doses, or placebo, will be given for 14 days. Blood samples, heart monitoring, vital signs, and imaging procedures will be performed.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Non-alcoholic Steatohepatitis, Non-alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Title

PF-06865571 100 mg

Arm Type

Experimental

Arm Title

PF-06865571 600 mg

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

tablet, 0 mg, 14 days, every 12 hours

Intervention Type

Drug

Intervention Name(s)

PF-06865571

Intervention Description

tablet, 50 mg, 14 days, every 12 hours

Intervention Type

Drug

Intervention Name(s)

PF-06865571

Intervention Description

tablet, 300 mg, 14 days, every 12 hours

Primary Outcome Measure Information:

Title

Relative Change From Baseline in Whole Liver Fat at Day 15 as Assessed by Magnetic Resonance Imaging (MRI) - Proton Density Fat Fraction (PDFF)

Description

MRI-PDFF is an established method that enables quantification of fat content in the liver. The value of whole liver fat as assessed by MRI-PDFF is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level.

Time Frame

Baseline (Day 1), Day 15

Secondary Outcome Measure Information:

Title

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

Description

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs.

Time Frame

From first dose of study treatment up to 28-35 days after last dose (maximum of up to 49 days)

Title

Number of Participants With Laboratory Test Abnormalities

Description

Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes); chemistry (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, sodium, potassium, calcium, chloride, bicarbonate); urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, urine erythrocytes, urine leukocytes, hyaline casts); biomarker (total cholesterol, low-density and high-density lipoprotein cholesterol, triglycerides, fasting glucose). Participants with any of the laboratory test abnormalities were counted.

Time Frame

From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days)

Title

Number of Participants With Vital Sign Abnormalities

Description

Vital sign categorical summarization criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine DBP greater than or equal to (>=) 20 mmHg; 5) change from baseline (increase or decrease) in supine SBP >=30 mmHg.

Time Frame

From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days)

Title

Number of Participants With Electrocardiogram (ECG) Abnormalities

Description

ECG categorical summarization criteria: 1) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): >=140 milliseconds (msec), >=50% change from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): >=300 msec, >=25% change when baseline is > 200 msec or >=50% change when baseline is less than or equal to (<=) 200 msec; 3) QTcF interval (heart rate corrected QT [time between the start of the ECG Q wave and the end of the T wave in the heart's electrical cycle] using Fridericia's formula): absolute value of >450 to 480 msec, >480 to 500 msec, >500 msec; a change from baseline of >30 to 60 msec or >60 msec.

Time Frame

From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days)

Title

Maximum Plasma Concentration (Cmax) For PF-06865571

Description

Cmax of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages.

Time Frame