A Double-blind Study to Assess 2 Doses of an Investigational Product for 16 Weeks in Participants With Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus

A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 3-ARM, PARALLEL GROUP STUDY TO EVALUATE SAFETY, TOLERABILITY AND PHARMACODYNAMICS OF PF-06835919 ADMINISTERED DAILY FOR 16 WEEKS IN ADULTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND TYPE 2 DIABETES MELLITUS ON METFORMIN

This is a double-blind, placebo-controlled study in adults with non-alcoholic steatohepatitis and Type 2 Diabetes Mellitis on stable dose of metformin monotherapy. Participants will be treated for 16 weeks with placebo or 1 of 2 doses of investigational product to determine the effect on liver fat, HbA1c, safety, tolerability and pharmacodynamics.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Steatohepatitis
• Intervention / Treatment: Drug: Placebo; Drug: PF-06835919; Drug: PF-06835919

• Study Type: Interventional
• Enrollment (Actual): 164
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1W4R4
    • Centre de Recherche Saint-Louis
  • Quebec, Canada, G1J 0H4
    • IRM Quebec
  • Quebec, Canada, G2J 0C4
    • Alpha Recherche Clinique Lebourgneuf
  • British Columbia
    • Victoria, British Columbia, Canada, V8T 5G4
      • Discovery Clinical Services Ltd.
    • Victoria, British Columbia, Canada, V8Z0B9
      • West Coast Medical Imaging
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Health Authority QE II Health Sciences Centre
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Nova Scotia Health Authority QE II Health Sciences Centre
    • Halifax, Nova Scotia, Canada, B3K 4N1
      • Nova Scotia Health Authority - Queen Elizabeth II Health Sciences Centre
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
      • Aggarwal and Associates Limited
    • London, Ontario, Canada, N6A 5B7
      • The Western Centre for Functional and Metabolic Mapping
    • Mississauga, Ontario, Canada, L5R 3K7
      • Oxford Medical Imaging
    • Sarnia, Ontario, Canada, N7T 4X3
      • Bluewater Clinical Research Group, Inc.
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre
  • Quebec
    • Chicoutimi, Quebec, Canada, G7H 7K9
      • Ecogene-21
    • Chicoutimi, Quebec, Canada, G7H 4J1
      • Resonance Magnetique du Saguenay-Lac-Saint-Jean
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre (MUHC)
    • Montreal, Quebec, Canada, H2L 4E9
      • Clinique de médecine Urbaine du Quartier Latin
    • Montreal, Quebec, Canada, H4A 3J1
      • MRI TTT Philips Radiation Oncology
    • Montreal, Quebec, Canada, H5B1B2
      • Radiologie Varad
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85295
      • Horizon Clinical Research Associates, PLLC
    • Tempe, Arizona, United States, 85207
      • Clinical Research Consortium an AMR company
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials LLC-Clinical Research
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research
    • Chula Vista, California, United States, 91911
      • San Diego Imaging SDI
    • Coronado, California, United States, 92118
      • Southern California Research Center
    • Coronado, California, United States, 92118
      • Sharp Coronado Hospital
    • Harbor City, California, United States, 90710
      • Holy Trinity Medical Clinic
    • Harbor City, California, United States, 90710
      • Innovative Clinical Research, Inc.
    • Inglewood, California, United States, 90301
      • ICM Medical Group
    • La Mesa, California, United States, 91942
      • eStudySite
    • Lincoln, California, United States, 95648
      • Clinical Trials Research
    • Los Angeles, California, United States, 90057
      • National Research Institute
    • Northridge, California, United States, 91328
      • Renaissance Imaging Medical Associates
    • Pasadena, California, United States, 91105
      • Huntington Medical Research Institute
    • Rialto, California, United States, 92377
      • Inland Empire Clinical Trials, LLC
    • Sacramento, California, United States, 95825
      • Diagnostic Radiological Imaging Sacramento
    • San Diego, California, United States, 92114
      • Precision Research Institute
    • San Diego, California, United States, 92123-2731
      • Sharp and Children's MRI Center, LLC
    • San Diego, California, United States, 92123
      • Sharp & Children's MRI Center, LLC
    • Santa Ana, California, United States, 92705
      • West Coast Radiology
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
    • Tarzana, California, United States, 91356
      • Liberty Pacific Advanced Imaging
    • Thousand Oaks, California, United States, 91360
      • Advanced Gastroenterology
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Incorporated
  • Florida
    • Atlantis, Florida, United States, 33461
      • Independant Imaging
    • Daytona Beach, Florida, United States, 32117
      • Twin Lakes Imaging
    • Doral, Florida, United States, 33122
      • Life Radiology
    • Hallandale Beach, Florida, United States, 33009
      • MD Clinical LLC
    • Jacksonville, Florida, United States, 32256
      • Borland Groover
    • Lake City, Florida, United States, 32055
      • Multi-Specialty Research Associates, Inc.
    • Miami, Florida, United States, 33126
      • Finlay Medical Research
    • Miami, Florida, United States, 33135
      • Suncoast Research Group, LLC
    • Miami, Florida, United States, 33145
      • Stand Up MRI of Miami
    • Miami, Florida, United States, 33015
      • Health Care Family Rehab and Research Center
    • Miami, Florida, United States, 33183
      • International Research Associates
    • Miami, Florida, United States, 33126
      • Clinical Research of Miami
    • Miami, Florida, United States, 33137
      • Unique Imaging
    • Miami, Florida, United States, 33144
      • Y & L Advance Health Care, Inc D/B/A Elite Clinical Research
    • Miami, Florida, United States, 33173
      • Vital Imaging Center
    • Miami, Florida, United States, 33173
      • Vital Imaging
    • Miami, Florida, United States, 33180
      • Unique Imaging
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
    • Palm Harbor, Florida, United States, 34684
      • Advanced Gastroenterology Associates, LLC
    • Palm Harbor, Florida, United States, 34685
      • Rose Radiology
    • Palm Springs, Florida, United States, 33406
      • Castillo & Torres MD PA
    • Palm Springs, Florida, United States, 33406
      • Ctmd Research Inc
    • Port Orange, Florida, United States, 32127
      • Progressive Medical Research
    • South Miami, Florida, United States, 33143
      • Qps-Mra, Llc
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Physicians Research Associates , LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • East-West Medical Research Institute
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Alliance Multispecialty Research, LLC
  • Michigan
    • Flint, Michigan, United States, 48504
      • AA MRC
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
    • Omaha, Nebraska, United States, 68198
      • Nebraska Medicine
  • Nevada
    • Las Vegas, Nevada, United States, 89109
      • Excel Clinical Research
    • Las Vegas, Nevada, United States, 89119
      • Alliance for Multispecialty, LLC
    • Las Vegas, Nevada, United States, 89128
      • Desert Radiology
    • Las Vegas, Nevada, United States, 89128
      • Pueblo Imaging
  • New York
    • Garden City, New York, United States, 11530
      • Northwell Imaging of Garden City
    • Manhasset, New York, United States, 11030
      • Northwell Health - Center for Liver Diseases and Transplantation
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston Salem
    • Winston-Salem, North Carolina, United States, 27103
      • Gastroenterology Associates of the Piedmont, PA
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
    • Cincinnati, Ohio, United States, 45227
      • ProScan
    • Marion, Ohio, United States, 43302
      • RAS Health
  • Texas
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes and Endocrine Research Center
    • Dallas, Texas, United States, 75231
      • Southwest Diagnostics Imaging Center
    • Houston, Texas, United States, 77081
      • Texas Center for Drug Development
    • Houston, Texas, United States, 77079
      • Endocrine Ips, Pllc
    • Houston, Texas, United States, 77024
      • PrimeCare Medical Group
    • Houston, Texas, United States, 77079
      • The Endocrine Center
    • Houston, Texas, United States, 77098
      • Houston Medical Imaging
    • Live Oak, Texas, United States, 78233
      • South Texas Radiology Imaging Centers
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas
    • San Antonio, Texas, United States, 78233
      • STRIC Northeast Imaging Center
    • Schertz, Texas, United States, 78154
      • Northeast Clinical Research of San Antonio, LLC (NECRSA, LLC)
  • Virginia
    • Richmond, Virginia, United States, 23236
      • Clinical Research Partners, LLC
    • Richmond, Virginia, United States, 23236
      • Virginia Endoscopy Group
    • Richmond, Virginia, United States, 23298
      • VCU Gateway Building Basement
    • Salem, Virginia, United States, 24153
      • Salem VA Medical Center
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center Investigational Drug Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males, or females of nonchildbearing potential
• 18 to 70 years of age
• Type 2 Diabetes Mellitus
• Liver fat >/=8% by MRI-PDFF
• On stable dose of metformin monotherapy for at least 2 months (at a dose of at least 500 mg daily)

Exclusion Criteria:

• History of other liver disease
• Unable to have an MRI performed
• Significant weight loss in the previous month and/or participant in current weight loss program
• History of diabetic complications with end-organ damage

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; Palacebo	Drug: Placebo; Placebo
EXPERIMENTAL: Low Dose; 150 mg	Drug: PF-06835919; 150 mg once daily; Drug: PF-06835919; 300 mg once daily
EXPERIMENTAL: High Dose; 300 mg	Drug: PF-06835919; 150 mg once daily; Drug: PF-06835919; 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 16	Whole liver fat was measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF).	Baseline, Week 16.
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16	A sufficient amount of blood was collected for the analysis of plasma HbA1c.	Baseline, Week 16.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious AE was any untoward medical occurrence at any dose that resulted in death; was life-threatening; required hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect or that was considered to be an important medical event. An AE was considered TEAE if the event occurred during the on-treatment period. The causality of AEs were assessed by the investigator using clinical judgement. A severe AE was an event that prevents normal everyday activities.	Up to 21 weeks.
Number of Participants With Hypoglycemia TEAEs	Hypoglycemic AEs were routinely monitored during participation in the study. Hypoglycemic AE was defined as 1 of the following: 1. Asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemic AE but a plasma glucose value of <70 milligram per deciliter (mg/dL) using glucometer; 2. Documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemic AEs were accompanied with a glucose value of <70 mg/dL using glucometer and the clinical picture included prompt resolution with food intake, subcutaneous glucagon or intravenous (IV) glucose; 3. Probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemic AEs were not accompanied by a plasma glucose determination but was presumably caused by a plasma glucose concentration of <70 mg/dL, and the clinical picture included prompt resolution with food intake, subcutaneous glucagon, or IV glucose.	Up to 21 weeks.
Cumulative Number of Participants With Clinical Laboratory Abnormalities	Clinical laboratory tests included hematology (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, platelet count, white blood cell count, total neutrophils, eosinophils, monocytes, basophils, lymphocytes); blood chemistry (blood urea nitrogen, creatinine, glucose, calcium, sodium, potassium, chloride, total bicarbonate, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, total bilirubin, alkaline phosphatase, uric acid, albumin, total protein); urinalysis (pH, glucose, protein, blood, ketones, nitrites, leukocyte esterase, urobilinogen, urine bilirubin, microscopy). The abnormality criteria were standard sponsor reporting criteria.	Up to 21 weeks.
Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria	Vital signs data meeting the following criteria were reported: sitting diastolic blood pressure (DBP) <50 mmHg or >= 20 mmHg increase or >= 20 mmHg decrease, sitting systolic blood pressure (SBP) blood pressure <90 mmHg or >=30 mmHg increase or >=30 mmHg decrease.	Up to 21 weeks.
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria	ECG data meeting the following criteria were reported: PR interval value >=300 msec, QRS interval percent change >= 50%, QTcF interval value >450 msec and <=480 msec, or change >30 msec and <=60 msec, or change >60 msec.	Up to 21 weeks.
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks	Blood samples were collected to ensure sufficient serum for the analysis of hs-CRP.	From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Change From Baseline in Fasting Insulin Over 16 Weeks	A sufficient amount of blood was collected for the analysis of plasma insulin. The unit of insulin is milli-international units per liter (mIU/L).	From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Change From Baseline in Fasting Glucose Over 16 Weeks	A sufficient amount of blood was collected for the analysis of plasma glucose.	From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks	HOMA-IR values were derived from fasting plasma insulin and glucose values. Greater reduction from baseline in HOMA-IR scale values shows greater effects on glycemic metabolism.	From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks	ALT was assessed as one of the clinical laboratory chemistry tests.	From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16.
Change From Baseline in HbA1c at All Timepoints Other Than Week 16	A sufficient amount of blood was collected for the analysis of plasma HbA1c.	From Baseline to Week 2, Week, 4, Week 8, and Week 12.

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): July 18, 2019
• Primary Completion (ACTUAL): March 2, 2021
• Study Completion (ACTUAL): March 30, 2021

Study Registration Dates

• First Submitted: May 28, 2019
• First Submitted That Met QC Criteria: May 28, 2019
• First Posted (ACTUAL): May 31, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 11, 2022
• Last Update Submitted That Met QC Criteria: April 18, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Non-alcoholic steatohepatitis; Type 2 Diabetes Mellitus
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: C1061011; DOSE RESPONSE IN PATIENTS (OTHER: Alias Study Number)

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