2-Week Study In People With Nonalcoholic Fatty Liver Disease

Study Overview
=================
Brief Summary
-----------------
2-week study in people with nonalcoholic fatty liver disease. Study drug at 1 of 2 doses, or placebo, will be given for 14 days. Blood samples, heart monitoring, vital signs, and imaging procedures will be performed.

Official Title
-----------------
A PHASE 1B, RANDOMIZED, DOUBLE-BLIND (SPONSOR-OPEN), PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACODYNAMICS AND PHARMACOKINETICS OF MULTIPLE ORAL DOSES OF PF- 06865571 FOR 2 WEEKS IN ADULTS WITH NONALCOHOLIC FATTY LIVER DISEASE

Conditions
-----------------
Non-alcoholic Steatohepatitis, Non-alcoholic Fatty Liver Disease

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: PF-06865571
* Drug: PF-06865571


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: controlled attenuation parameter greater than or equal to 260 dB/m via FibroScan liver fat greater than or equal to 6% via MRI Exclusion Criteria: Chronic liver disease Type 2 diabetes requiring drug treatment Unable to undergo MRI History of heart attack or stroke

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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> | Drug: Placebo<br>* tablet, 0 mg, 14 days, every 12 hours<br>|
| Experimental: PF-06865571 100 mg<br> | Drug: PF-06865571<br>* tablet, 50 mg, 14 days, every 12 hours<br>|
| Experimental: PF-06865571 600 mg<br> | Drug: PF-06865571<br>* tablet, 300 mg, 14 days, every 12 hours<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change From Baseline in Whole Liver Fat at Day 15 as Assessed by Magnetic Resonance Imaging (MRI) - Proton Density Fat Fraction (PDFF) | MRI-PDFF is an established method that enables quantification of fat content in the liver. The value of whole liver fat as assessed by MRI-PDFF is expressed in percentage and ranges from 0 to 100% with higher values representing higher liver fat level. | Baseline (Day 1), Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening (immediate risk of death); initial or prolonged inpatient hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect. Treatment-emergent AEs were those with initial onset or increasing in severity on or after the first dose of investigational product administration. AEs included both SAEs and non-serious AEs. | From first dose of study treatment up to 28-35 days after last dose (maximum of up to 49 days) | 
| Number of Participants With Laboratory Test Abnormalities | Following laboratory parameters were assessed against pre-defined abnormality criteria: hematology (hemoglobin, hematocrit, erythrocytes, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, platelets, leukocytes, lymphocytes, neutrophils, basophils, eosinophils, monocytes); chemistry (total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transferase, alkaline phosphatase, protein, albumin, urea nitrogen, creatinine, urate, sodium, potassium, calcium, chloride, bicarbonate); urinalysis (urine glucose, ketones, urine protein, urine hemoglobin, urobilinogen, urine bilirubin, nitrite, urine erythrocytes, urine leukocytes, hyaline casts); biomarker (total cholesterol, low-density and high-density lipoprotein cholesterol, triglycerides, fasting glucose). Participants with any of the laboratory test abnormalities were counted. | From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days) | 
| Number of Participants With Vital Sign Abnormalities | Vital sign categorical summarization criteria: 1) supine systolic blood pressure (SBP) <90 millimeters of mercury (mmHg); 2) supine diastolic blood pressure (DBP) <50 mmHg; 3) pulse rate <40 or >120 beats per minute (bpm); 4) change from baseline (increase or decrease) in supine DBP greater than or equal to (>=) 20 mmHg; 5) change from baseline (increase or decrease) in supine SBP >=30 mmHg. | From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days) | 
| Number of Participants With Electrocardiogram (ECG) Abnormalities | ECG categorical summarization criteria: 1) QRS interval (time from ECG Q wave to the end of the S wave corresponding to ventricle depolarization): >=140 milliseconds (msec), >=50% change from baseline; 2) PR interval (the interval between the start of the P wave and the start of the QRS complex, corresponding to the time between the onset of the atrial depolarization and onset of ventricular depolarization): >=300 msec, >=25% change when baseline is > 200 msec or >=50% change when baseline is less than or equal to (<=) 200 msec; 3) QTcF interval (heart rate corrected QT [time between the start of the ECG Q wave and the end of the T wave in the heart's electrical cycle] using Fridericia's formula): absolute value of >450 to 480 msec, >480 to 500 msec, >500 msec; a change from baseline of >30 to 60 msec or >60 msec. | From first dose of study treatment up to 7-10 days after last dose (maximum of up to 24 days) | 
| Maximum Plasma Concentration (Cmax) For PF-06865571 | Cmax of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages. | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | 
| Area Under the Plasma Concentration-Time Profile Over the Dosing Interval (AUCtau) For PF-06865571 | AUCtau of PF-06865571 on Day 14 was obtained by linear/log trapezoidal method. The dosing interval (tau) was 12 hours. Geometric coefficients of variations were reported as percentages. | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | 
| Time to Reach Maximum Plasma Concentration (Tmax) For PF-06865571 | Tmax of PF-06865571 on Day 14 was observed directly from data as time of Cmax occurrence. | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | 
| Minimum Plasma Concentration (Cmin) For PF-06865571 | Cmin of PF-06865571 on Day 14 was observed directly from data. Geometric coefficients of variations were reported as percentages. | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | 
| Apparent Oral Clearance (CL/F) For PF-06865571 | CL/F of PF-06865571 on Day 14 was calculated as Dose/AUCtau. Geometric coefficients of variations were reported as percentages. | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose | 
| Peak-to-Trough Ratio (PTR) For PF-06865571 | PTR of PF-06865571 on Day 14 was calculated as Cmax/Cmin. Geometric coefficients of variations were reported as percentages. | Day 14 pre-dose, and 1, 2, 3, 4, 6, 8, 12 hours post-dose |