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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Placebo
* Drug: PF-06835919
* Drug: PF-06835919


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Palacebo | Drug: Placebo<br>* Placebo<br>|
| Experimental: Low Dose<br>150 mg | Drug: PF-06835919<br>* 150 mg once daily<br>|
| Experimental: High Dose<br>300 mg | Drug: PF-06835919<br>* 300 mg once daily<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-alcoholic steatohepatitis; Type 2 Diabetes Mellitus