6-week Safety and PD Study in Adults With NAFLD

Study Overview
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Brief Summary
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IN THIS PHASE 2A, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED, 3 ARM, PARALLEL- GROUP STUDY, SAFETY, TOLERABILITY, AND PHARMACODYNAMICS OF PF-06835919 ADMINISTERED ONCE DAILY FOR 6 WEEKS WILL BE ASSESSED IN ADULTS WITH NONALCOHOLIC FATTY LIVER DISEASE

Official Title
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A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, 3-ARM, PARALLEL- GROUP STUDY TO EVALUATE THE SAFETY, TOLERABILITY, AND PHARMACODYNAMICS OF PF-06835919 ADMINISTERED ONCE DAILY FOR 6 WEEKS IN ADULTS WITH NONALCOHOLIC FATTY LIVER DISEASE

Conditions
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Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: PF-06835919 Low Dose
* Drug: PF-06835919 High Dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI at least 28 kg/m2 Type 2 diabetes and/or metabolic syndrome Exclusion Criteria: Liver disease Type 1 diabetes Recent heart attack or stroke Inability to have an MRI scan

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 0 mg<br>|
| Experimental: PF-06835919 Low Dose<br>75 mg once daily | Drug: PF-06835919 Low Dose<br>* 75 mg once daily<br>|
| Experimental: PF-06835919 High Dose<br>300 mg once daily | Drug: PF-06835919 High Dose<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 6 | The percent change from baseline in whole liver fat at Week 6 was assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF). MRI-PDFF generates measures of the fraction of mobile protons in the liver attributable to fat content and provides whole liver coverage so that fat content can be assessed across 8 Couinaud liver segments. Whole liver PDFF was calculated as follows: Whole Liver PDFF= PDFFs for (Segment I+Segment II+Segment III+Segment IVa+Segment IVb+Segment V+Segment VI+Segment+VII+Segment VIII) / (number of segments assessed). The same segments were to be used at both baseline and post-baseline time points in the calculation of whole liver PDFF to derive the percent change from baseline. The values of whole liver PDFF ranges from 0 to 100 and higher values represent higher liver fat. | Baseline and Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | All-causality adverse events (AEs) were any untoward medical occurrence in a study participant who administered a product or medical device, the event need not necessarily have a causal relationship with the treatment or usage. Treatment-related AEs were any untoward medical occurrence in a study participant who administered a product or medical device, the event needed to have a causal relationship with the treatment or usage. A TEAE was defined as any event not present prior to the initiation of the treatments or any event already present that worsens in either intensity or frequency following exposure to the treatments. | Baseline up to Day 77 (28-35 days post last dose) | 
| Number of Participants With Post-dose Vital Signs Data Meeting Categorical Criteria | The vital sign categorical criteria included: Sitting DBP (diastolic blood pressure) millimeter of mercury (mmHg) Change >= 20 mmHg increase Sitting SBP (systolic blood pressure) (mmHg) Change >= 30 mmHg increase Sitting DBP (mmHg) Change >= 20 mmHg decrease Sitting SBP (mmHg) Change >= 30 mmHg decrease Sitting DBP (mmHg) Value < 50 mmHg Sitting Pulse Rate (bpm) Value < 40 bpm or Value > 120 bpm Sitting SBP (mmHg) Value < 90 mmHg | Baseline up to Day 56 (Week 8) | 
| Number of Participants With Post-dose ECG Data Meeting Categorical Criteria | The ECG categorical criteria included: PR Interval (msec) percent (%)Change >= 25% increase when baseline >200 or >=50% increase when baseline <=200 QRS Interval (msec) %Change >= 50% increase QTcF Interval (Fridericia's Correction) (msec) increase 30 <= Change < 60 or Change >= 60 PR Interval (msec) Value >= 300 QRS Interval (msec) Value >= 140 QTcF Interval (Fridericia's Correction) (msec) 450 <= Value <480 or 480 <=Value <500 or Value >= 500 | Baseline up to Day 56 (Week 8) | 
| Number of Participants With Laboratory Abnormalities | Below parameters were evaluated for laboratory tests: Hemoglobin, Hematocrit, Erythrocytes, Ery. Mean Copuscular Volume, Ery. Mean Copuscular Hemoglobin, Ery. Mean Corpuscular HGB Concentration, Platelets, Leukocytes, Lymphocytes, Neuprophils, Basophils, Eosinophils, Monocytes, Bilirubin, Direct Biliirubin, Indirect Bilirubin, Aspartate Aminotransferase, Alanine Aminotransferase, Gamma Glutamyl Transferase, Alkaline Phosphatase, Protein, Albumin, Albumin, Blood Urea Nitrogen, Creatinine, Urate, Sodium, Potassium, Chloride, Calcium, Bicarbonate, Glucose-Fasting, pH, Urine Glucose, Ketone, Urine Protein, Urine Hemoglobin, Urobilinogen, Urine Bilirubin, Nitrite, Leukocyte Esterase, Urine Erythocytes, Urine leukocytes, Hyaline Casts, Urine Creatinine. | Baseline up to Day 56 (Week 8) |