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
- Conditions
- Non-alcoholic Steatohepatitis
- Interventions
- Drug: PF-06835919Drug: Placebo
- Registration Number
- NCT03969719
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 164
- 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Low Dose PF-06835919 150 mg Placebo Placebo Palacebo High Dose PF-06835919 300 mg
- Primary Outcome Measures
Name Time Method Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 Baseline, Week 16. A sufficient amount of blood was collected for the analysis of plasma HbA1c.
Percent Change From Baseline in Whole Liver Fat at Week 16 Baseline, Week 16. Whole liver fat was measured by Magnetic Resonance Imaging-Proton Density Fat Fraction (MRI-PDFF).
- Secondary Outcome Measures
Name Time Method Number of Participants With Hypoglycemia TEAEs Up to 21 weeks. 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.
Change From Baseline in Fasting Insulin Over 16 Weeks From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. 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).
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Up to 21 weeks. 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.
Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-Specified Criteria Up to 21 weeks. 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.
Change From Baseline in Fasting Glucose Over 16 Weeks From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. A sufficient amount of blood was collected for the analysis of plasma glucose.
Cumulative Number of Participants With Clinical Laboratory Abnormalities Up to 21 weeks. 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.
Number of Participants With Vital Signs Data Meeting Pre-Specified Criteria Up to 21 weeks. 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.
Percent Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) Over 16 Weeks From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. Blood samples were collected to ensure sufficient serum for the analysis of hs-CRP.
Change From Baseline in Fasting Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) Over 16 Weeks From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. 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.
Percent Change From Baseline in Alanine Aminotransferase (ALT) Over 16 Weeks From Baseline to Week 2, Week, 4, Week 8, Week 12 and Week 16. ALT was assessed as one of the clinical laboratory chemistry tests.
Change From Baseline in HbA1c at All Timepoints Other Than Week 16 From Baseline to Week 2, Week, 4, Week 8, and Week 12. A sufficient amount of blood was collected for the analysis of plasma HbA1c.
Trial Locations
- Locations (104)
The Western Centre for Functional and Metabolic Mapping
🇨🇦London, Ontario, Canada
Hope Clinical Research
🇺🇸Canoga Park, California, United States
eStudySite
🇺🇸La Mesa, California, United States
Clinical Trials Research
🇺🇸Lincoln, California, United States
Sharp Coronado Hospital
🇺🇸Coronado, California, United States
ICM Medical Group
🇺🇸Inglewood, California, United States
Southern California Research Center
🇺🇸Coronado, California, United States
Holy Trinity Medical Clinic
🇺🇸Harbor City, California, United States
Diagnostic Radiological Imaging Sacramento
🇺🇸Sacramento, California, United States
Huntington Medical Research Institute
🇺🇸Pasadena, California, United States
Liberty Pacific Advanced Imaging
🇺🇸Tarzana, California, United States
Encompass Clinical Research
🇺🇸Spring Valley, California, United States
Advanced Gastroenterology
🇺🇸Thousand Oaks, California, United States
Northwell Imaging of Garden City
🇺🇸Garden City, New York, United States
PMG Research of Wilmington
🇺🇸Wilmington, North Carolina, United States
Gastroenterology Associates of the Piedmont, PA
🇺🇸Winston-Salem, North Carolina, United States
PMG Research of Winston Salem
🇺🇸Winston-Salem, North Carolina, United States
RAS Health
🇺🇸Marion, Ohio, United States
South Texas Radiology Imaging Centers
🇺🇸Live Oak, Texas, United States
Northeast Clinical Research of San Antonio, LLC (NECRSA, LLC)
🇺🇸Schertz, Texas, United States
Clinical Research Partners, LLC
🇺🇸Richmond, Virginia, United States
Virginia Endoscopy Group
🇺🇸Richmond, Virginia, United States
VCU Gateway Building Basement
🇺🇸Richmond, Virginia, United States
Salem VA Medical Center
🇺🇸Salem, Virginia, United States
Anaheim Clinical Trials LLC-Clinical Research
🇺🇸Anaheim, California, United States
Anaheim Clinical Trials, LLC
🇺🇸Anaheim, California, United States
National Research Institute
🇺🇸Los Angeles, California, United States
Precision Research Institute
🇺🇸San Diego, California, United States
Sharp and Children's MRI Center, LLC
🇺🇸San Diego, California, United States
West Coast Radiology
🇺🇸Santa Ana, California, United States
University Clinical Investigators, Incorporated
🇺🇸Tustin, California, United States
Panax Clinical Research
🇺🇸Miami Lakes, Florida, United States
Health Care Family Rehab and Research Center
🇺🇸Miami, Florida, United States
CTI Clinical Research Center
🇺🇸Cincinnati, Ohio, United States
Clinical Research of Miami
🇺🇸Miami, Florida, United States
Finlay Medical Research
🇺🇸Miami, Florida, United States
Pueblo Imaging
🇺🇸Las Vegas, Nevada, United States
AA MRC
🇺🇸Flint, Michigan, United States
Southwest Diagnostics Imaging Center
🇺🇸Dallas, Texas, United States
ProScan
🇺🇸Cincinnati, Ohio, United States
Dallas Diabetes and Endocrine Research Center
🇺🇸Dallas, Texas, United States
PrimeCare Medical Group
🇺🇸Houston, Texas, United States
Endocrine IPS, PLLC
🇺🇸Houston, Texas, United States
The Endocrine Center
🇺🇸Houston, Texas, United States
Texas Center for Drug Development
🇺🇸Houston, Texas, United States
Clinical Trials of Texas
🇺🇸San Antonio, Texas, United States
STRIC Northeast Imaging Center
🇺🇸San Antonio, Texas, United States
Harborview Medical Center Investigational Drug Services
🇺🇸Seattle, Washington, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Toronto Liver Centre
🇨🇦Toronto, Ontario, Canada
East-West Medical Research Institute
🇺🇸Honolulu, Hawaii, United States
Alliance Multispecialty Research, LLC
🇺🇸Wichita, Kansas, United States
Innovative Clinical Research, Inc.
🇺🇸Harbor City, California, United States
Renaissance Imaging Medical Associates
🇺🇸Northridge, California, United States
Inland Empire Clinical Trials, LLC
🇺🇸Rialto, California, United States
Sharp & Children's MRI Center, LLC
🇺🇸San Diego, California, United States
MD Clinical LLC
🇺🇸Hallandale Beach, Florida, United States
Unique Imaging
🇺🇸Miami, Florida, United States
Suncoast Research Group, LLC
🇺🇸Miami, Florida, United States
Qps-Mra, Llc
🇺🇸South Miami, Florida, United States
Ctmd Research Inc
🇺🇸Palm Springs, Florida, United States
Physicians Research Associates , LLC
🇺🇸Lawrenceville, Georgia, United States
Excel Clinical Research
🇺🇸Las Vegas, Nevada, United States
Northwell Health - Center for Liver Diseases and Transplantation
🇺🇸Manhasset, New York, United States
Houston Medical Imaging
🇺🇸Houston, Texas, United States
University of Washington Medical Center
🇺🇸Seattle, Washington, United States
Nova Scotia Health Authority - Queen Elizabeth II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Centre de Recherche Saint-Louis
🇨🇦Quebec, Canada
IRM Quebec
🇨🇦Quebec, Canada
ALPHA Recherche Clinique Lebourgneuf
🇨🇦Quebec, Canada
Horizon Clinical Research Associates, PLLC
🇺🇸Gilbert, Arizona, United States
Clinical Research Consortium an AMR company
🇺🇸Tempe, Arizona, United States
Life Radiology
🇺🇸Doral, Florida, United States
Borland Groover
🇺🇸Jacksonville, Florida, United States
Independant Imaging
🇺🇸Atlantis, Florida, United States
Twin Lakes Imaging
🇺🇸Daytona Beach, Florida, United States
Multi-Specialty Research Associates, Inc.
🇺🇸Lake City, Florida, United States
Y & L Advance Health Care, Inc D/B/A Elite Clinical Research
🇺🇸Miami, Florida, United States
Discovery Clinical Services Ltd.
🇨🇦Victoria, British Columbia, Canada
Oxford Medical Imaging
🇨🇦Mississauga, Ontario, Canada
Resonance Magnetique du Saguenay-Lac-Saint-Jean
🇨🇦Chicoutimi, Quebec, Canada
Ecogene-21
🇨🇦Chicoutimi, Quebec, Canada
Clinique de Medecine Urbaine du Quartier Latin
🇨🇦Montreal, Quebec, Canada
McGill University Health Centre (MUHC)
🇨🇦Montreal, Quebec, Canada
MRI TTT Philips Radiation Oncology
🇨🇦Montreal, Quebec, Canada
Radiologie Varad
🇨🇦Montreal, Quebec, Canada
Stand Up MRI of Miami
🇺🇸Miami, Florida, United States
Vital Imaging Center
🇺🇸Miami, Florida, United States
Nebraska Medicine
🇺🇸Omaha, Nebraska, United States
Vital Imaging
🇺🇸Miami, Florida, United States
International Research Associates
🇺🇸Miami, Florida, United States
West Coast Medical Imaging
🇨🇦Victoria, British Columbia, Canada
Aggarwal and Associates Limited
🇨🇦Brampton, Ontario, Canada
St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Advanced Gastroenterology Associates, LLC
🇺🇸Palm Harbor, Florida, United States
Rose Radiology
🇺🇸Palm Harbor, Florida, United States
Progressive Medical Research
🇺🇸Port Orange, Florida, United States
Alliance for Multispecialty, LLC
🇺🇸Las Vegas, Nevada, United States
Desert Radiology
🇺🇸Las Vegas, Nevada, United States
Nova Scotia Health Authority QE II Health Sciences Centre
🇨🇦Halifax, Nova Scotia, Canada
Castillo & Torres MD PA
🇺🇸Palm Springs, Florida, United States
Bluewater Clinical Research Group, Inc.
🇨🇦Sarnia, Ontario, Canada
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
San Diego Imaging SDI
🇺🇸Chula Vista, California, United States