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

Non-alcoholic Steatohepatitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03969719
• Other study ID #: C1061011
• Secondary ID: DOSE RESPONSE IN
• Status: Completed
• Phase: Phase 2
• Start date: July 18, 2019
• Est. completion date: March 30, 2021

Study information

• Verified date: April 2022
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: March 30, 2021
• Est. primary completion date: March 2, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Non-alcoholic Steatohepatitis

Intervention

Drug:
• Placebo
Placebo
• PF-06835919
150 mg once daily
• PF-06835919
300 mg once daily

Locations

Country	Name	City	State
Canada	Aggarwal and Associates Limited	Brampton	Ontario
Canada	Ecogene-21	Chicoutimi	Quebec
Canada	Resonance Magnetique du Saguenay-Lac-Saint-Jean	Chicoutimi	Quebec
Canada	Nova Scotia Health Authority - Queen Elizabeth II Health Sciences Centre	Halifax	Nova Scotia
Canada	Nova Scotia Health Authority QE II Health Sciences Centre	Halifax	Nova Scotia
Canada	Nova Scotia Health Authority QE II Health Sciences Centre	Halifax	Nova Scotia
Canada	The Western Centre for Functional and Metabolic Mapping	London	Ontario
Canada	Oxford Medical Imaging	Mississauga	Ontario
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	ALPHA Recherche Clinique Lebourgneuf	Quebec
Canada	Centre de Recherche Saint-Louis	Quebec
Canada	IRM Quebec	Quebec
Canada	Bluewater Clinical Research Group, Inc.	Sarnia	Ontario
Canada	St. Michael's Hospital	Toronto	Ontario
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	Discovery Clinical Services Ltd.	Victoria	British Columbia
Canada	West Coast Medical Imaging	Victoria	British Columbia
United States	Anaheim Clinical Trials LLC-Clinical Research	Anaheim	California
United States	Anaheim Clinical Trials, LLC	Anaheim	California
United States	Independant Imaging	Atlantis	Florida
United States	Hope Clinical Research	Canoga Park	California
United States	San Diego Imaging SDI	Chula Vista	California
United States	CTI Clinical Research Center	Cincinnati	Ohio
United States	ProScan	Cincinnati	Ohio
United States	Sharp Coronado Hospital	Coronado	California
United States	Southern California Research Center	Coronado	California
United States	Dallas Diabetes and Endocrine Research Center	Dallas	Texas
United States	Southwest Diagnostics Imaging Center	Dallas	Texas
United States	Twin Lakes Imaging	Daytona Beach	Florida
United States	Life Radiology	Doral	Florida
United States	AA MRC	Flint	Michigan
United States	Northwell Imaging of Garden City	Garden City	New York
United States	Horizon Clinical Research Associates, PLLC	Gilbert	Arizona
United States	MD Clinical LLC	Hallandale Beach	Florida
United States	Holy Trinity Medical Clinic	Harbor City	California
United States	Innovative Clinical Research, Inc.	Harbor City	California
United States	East-West Medical Research Institute	Honolulu	Hawaii
United States	Endocrine IPS, PLLC	Houston	Texas
United States	Houston Medical Imaging	Houston	Texas
United States	PrimeCare Medical Group	Houston	Texas
United States	Texas Center for Drug Development	Houston	Texas
United States	The Endocrine Center	Houston	Texas
United States	ICM Medical Group	Inglewood	California
United States	Borland Groover	Jacksonville	Florida
United States	eStudySite	La Mesa	California
United States	Multi-Specialty Research Associates, Inc.	Lake City	Florida
United States	Alliance for Multispecialty, LLC	Las Vegas	Nevada
United States	Desert Radiology	Las Vegas	Nevada
United States	Excel Clinical Research	Las Vegas	Nevada
United States	Pueblo Imaging	Las Vegas	Nevada
United States	Physicians Research Associates , LLC	Lawrenceville	Georgia
United States	Clinical Trials Research	Lincoln	California
United States	South Texas Radiology Imaging Centers	Live Oak	Texas
United States	National Research Institute	Los Angeles	California
United States	Northwell Health - Center for Liver Diseases and Transplantation	Manhasset	New York
United States	RAS Health	Marion	Ohio
United States	Clinical Research of Miami	Miami	Florida
United States	Finlay Medical Research	Miami	Florida
United States	Health Care Family Rehab and Research Center	Miami	Florida
United States	International Research Associates	Miami	Florida
United States	Stand Up MRI of Miami	Miami	Florida
United States	Suncoast Research Group, LLC	Miami	Florida
United States	Unique Imaging	Miami	Florida
United States	Unique Imaging	Miami	Florida
United States	Vital Imaging	Miami	Florida
United States	Vital Imaging Center	Miami	Florida
United States	Y & L Advance Health Care, Inc D/B/A Elite Clinical Research	Miami	Florida
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Renaissance Imaging Medical Associates	Northridge	California
United States	Nebraska Medicine	Omaha	Nebraska
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Advanced Gastroenterology Associates, LLC	Palm Harbor	Florida
United States	Rose Radiology	Palm Harbor	Florida
United States	Castillo & Torres MD PA	Palm Springs	Florida
United States	Ctmd Research Inc	Palm Springs	Florida
United States	Huntington Medical Research Institute	Pasadena	California
United States	Progressive Medical Research	Port Orange	Florida
United States	Inland Empire Clinical Trials, LLC	Rialto	California
United States	Clinical Research Partners, LLC	Richmond	Virginia
United States	VCU Gateway Building Basement	Richmond	Virginia
United States	Virginia Endoscopy Group	Richmond	Virginia
United States	Diagnostic Radiological Imaging Sacramento	Sacramento	California
United States	Salem VA Medical Center	Salem	Virginia
United States	Clinical Trials of Texas	San Antonio	Texas
United States	STRIC Northeast Imaging Center	San Antonio	Texas
United States	Precision Research Institute	San Diego	California
United States	Sharp & Children's MRI Center, LLC	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	Northeast Clinical Research of San Antonio, LLC (NECRSA, LLC)	Schertz	Texas
United States	Harborview Medical Center	Seattle	Washington
United States	Harborview Medical Center Investigational Drug Services	Seattle	Washington
United States	University of Washington Medical Center	Seattle	Washington
United States	Qps-Mra, Llc	South Miami	Florida
United States	Encompass Clinical Research	Spring Valley	California
United States	Liberty Pacific Advanced Imaging	Tarzana	California
United States	Clinical Research Consortium an AMR company	Tempe	Arizona
United States	Advanced Gastroenterology	Thousand Oaks	California
United States	University Clinical Investigators, Incorporated	Tustin	California
United States	Alliance Multispecialty Research, LLC	Wichita	Kansas
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

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.

External Links

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