6-week Safety and PD Study in Adults With NAFLD

A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 3-ARM, PARALLEL- GROUP STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACODYNAMICS OF PF-06835919 ADMINISTERED ONCE DAILY FOR 6 WEEKS IN ADULTS WITH NONALCOHOLIC FATTY LIVER DISEASE

IN THIS PHASE 2A, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED, 3 ARM, PARALLEL- GROUP STUDY, SAFETY, TOLERABILITY, AND PHARMACODYNAMICS OF PF-06835919 ADMINISTERED ONCE DAILY FOR 6 WEEKS WILL BE ASSESSED IN ADULTS WITH NONALCOHOLIC FATTY LIVER DISEASE

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Placebo; Drug: PF-06835919 Low Dose; Drug: PF-06835919 High Dose

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90057
      • National Research Institute
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Miami, Florida, United States, 33145
      • Stand-Up MRI of Miami
    • Orange City, Florida, United States, 32763
      • Avail Clinical Research, LLC
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Sterling Research Group, Ltd.
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch LLC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, Inc.
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clinical Research, 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:

• BMI at least 28 kg/m2
• Type 2 diabetes and/or metabolic syndrome

Exclusion Criteria:

• Liver disease
• Type 1 diabetes
• Recent heart attack or stroke
• Inability to have an MRI scan

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; 0 mg
Experimental: PF-06835919 Low Dose; 75 mg once daily	Drug: PF-06835919 Low Dose; 75 mg once daily
Experimental: PF-06835919 High Dose; 300 mg once daily	Drug: PF-06835919 High Dose; 300 mg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Whole Liver Fat at Week 6	The percent change from baseline in whole liver fat at Week 6 was assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF). MRI-PDFF generates measures of the fraction of mobile protons in the liver attributable to fat content and provides whole liver coverage so that fat content can be assessed across 8 Couinaud liver segments. Whole liver PDFF was calculated as follows: Whole Liver PDFF= PDFFs for (Segment I+Segment II+Segment III+Segment IVa+Segment IVb+Segment V+Segment VI+Segment+VII+Segment VIII) / (number of segments assessed). The same segments were to be used at both baseline and post-baseline time points in the calculation of whole liver PDFF to derive the percent change from baseline. The values of whole liver PDFF ranges from 0 to 100 and higher values represent higher liver fat.	Baseline and Week 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	All-causality adverse events (AEs) were any untoward medical occurrence in a study participant who administered a product or medical device, the event need not necessarily have a causal relationship with the treatment or usage. Treatment-related AEs were any untoward medical occurrence in a study participant who administered a product or medical device, the event needed to have a causal relationship with the treatment or usage. A TEAE was defined as any event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments.	Baseline up to Day 77 (28-35 days post last dose)
Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria	The vital sign categorical criteria included: Sitting DBP (diastolic blood pressure) millimeter of mercury (mmHg) Change >= 20 mmHg increase Sitting SBP (systolic blood pressure) (mmHg) Change >= 30 mmHg increase Sitting DBP (mmHg) Change >= 20 mmHg decrease Sitting SBP (mmHg) Change >= 30 mmHg decrease Sitting DBP (mmHg) Value < 50 mmHg Sitting Pulse Rate (bpm) Value < 40 bpm or Value > 120 bpm Sitting SBP (mmHg) Value < 90 mmHg	Baseline up to Day 56 (Week 8)
Number of Participants With Post-dose ECG Data Meeting Categorical Criteria	The ECG categorical criteria included: PR Interval (msec) percent (%)Change >= 25% increase when baseline >200 or >=50% increase when baseline <=200 QRS Interval (msec) %Change >= 50% increase QTcF Interval (Fridericia's Correction) (msec) increase 30 <= Change < 60 or Change >= 60 PR Interval (msec) Value >= 300 QRS Interval (msec) Value >= 140 QTcF Interval (Fridericia's Correction) (msec) 450 <= Value <480 or 480 <=Value <500 or Value >= 500	Baseline up to Day 56 (Week 8)
Number of Participants With Laboratory Abnormalities	Below parameters were evaluated for laboratory tests: Hemoglobin, Hematocrit, Erythrocytes, Ery. Mean Copuscular Volume, Ery. Mean Copuscular Hemoglobin, Ery. Mean Corpuscular HGB Concentration, Platelets, Leukocytes, Lymphocytes, Neuprophils, Basophils, Eosinophils, Monocytes, Bilirubin, Direct Biliirubin, Indirect Bilirubin, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase, Alkaline Phosphatase, Protein, Albumin, Albumin, Blood Urea Nitrogen, Creatinine, Urate, Sodium, Potassium, Chloride, Calcium, Bicarbonate, Glucose-Fasting, pH, Urine Glucose, Ketone, Urine Protein, Urine Hemoglobin, Urobilinogen, Urine Bilirubin, Nitrite, Leukocyte Esterase, Urine Erythocytes, Urine leukocytes, Hyaline Casts, Urine Creatinine.	Baseline up to Day 56 (Week 8)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Kazierad DJ, Chidsey K, Somayaji VR, Bergman AJ, Birnbaum MJ, Calle RA. Inhibition of ketohexokinase in adults with NAFLD reduces liver fat and inflammatory markers: A randomized phase 2 trial. Med (N Y). 2021 Jul 9;2(7):800-813.e3. doi: 10.1016/j.medj.2021.04.007. Epub 2021 Apr 27.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2017
• Primary Completion (Actual): March 30, 2018
• Study Completion (Actual): April 27, 2018

Study Registration Dates

• First Submitted: August 16, 2017
• First Submitted That Met QC Criteria: August 18, 2017
• First Posted (Actual): August 22, 2017

Study Record Updates

• Last Update Posted (Actual): April 4, 2019
• Last Update Submitted That Met QC Criteria: March 12, 2019
• Last Verified: March 1, 2019

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: C1061003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• 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