2-Week Study In People With Nonalcoholic Fatty Liver Disease

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

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.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease; Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: Placebo; Drug: PF-06865571; Drug: PF-06865571

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • New Haven Clinical Research Unit
  • Florida
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc
  • Nevada
    • Las Vegas, Nevada, United States, 89113
      • PPD Development, LP
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; tablet, 0 mg, 14 days, every 12 hours
EXPERIMENTAL: PF-06865571 100 mg	Drug: PF-06865571; tablet, 50 mg, 14 days, every 12 hours; Drug: PF-06865571; tablet, 300 mg, 14 days, every 12 hours
EXPERIMENTAL: PF-06865571 600 mg	Drug: PF-06865571; tablet, 50 mg, 14 days, every 12 hours; Drug: PF-06865571; tablet, 300 mg, 14 days, every 12 hours

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline (Day 1), Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From first dose of study treatment up to 28-35 days after last dose (maximum of up to 49 days)
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.	From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days)
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.	From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days)
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.	From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days)
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.	Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
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.	Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
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.	Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
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.	Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
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.	Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose
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.	Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose

Collaborators and Investigators

• Sponsor: 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): June 21, 2018
• Primary Completion (ACTUAL): March 8, 2019
• Study Completion (ACTUAL): April 4, 2019

Study Registration Dates

• First Submitted: April 19, 2018
• First Submitted That Met QC Criteria: April 19, 2018
• First Posted (ACTUAL): May 1, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 13, 2020
• Last Update Submitted That Met QC Criteria: February 28, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: C2541005

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: Yes
• Studies a U.S. FDA-regulated device product: No