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
- 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)
Horizon Clinical Research Associates, PLLC
🇺🇸Gilbert, Arizona, United States
Clinical Research Consortium an AMR company
🇺🇸Tempe, Arizona, United States
Anaheim Clinical Trials LLC-Clinical Research
🇺🇸Anaheim, California, United States
Anaheim Clinical Trials, LLC
🇺🇸Anaheim, California, United States
Hope Clinical Research
🇺🇸Canoga Park, California, United States
San Diego Imaging SDI
🇺🇸Chula Vista, California, United States
Sharp Coronado Hospital
🇺🇸Coronado, California, United States
Southern California Research Center
🇺🇸Coronado, California, United States
Holy Trinity Medical Clinic
🇺🇸Harbor City, California, United States
Innovative Clinical Research, Inc.
🇺🇸Harbor City, California, United States
Scroll for more (94 remaining)Horizon Clinical Research Associates, PLLC🇺🇸Gilbert, Arizona, United States