PF-06865571

MRI-PDFF technique is an established method that enables quantification of fat content in the liver. It measures 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 = the sum of PDFFs for (Segment I + Segment II + Segment III + Segment IVa + Segment IVb + Segment V + Segment VI + Segment VII + Segment VIII) divided by (number of segments assessed and no missing/mapping at Baseline, and on Week 6). If some segments did not have results reported at Baseline and/or Week 6, liver PDFF was to be calculated using data in segments that had data available at both Baseline visit and Week 6 visit. For this outcome measure (OM), baseline is defined as the assessment undertaken between Visit 3/Week -2 and Visit 4/Day 1.

NASH resolution: disappearance of ballooning (Nonalcoholic Fatty Liver Disease \[NAFLD\] Activity Score \[NAS\] ballooning score=0;0=no ballooning,1=few balloon cells,2=many cells with prominent ballooning; higher scores(HS)=more disease activity \[DA\]),residual/no lobular inflammation(NAS lobular inflammation score 0/1,0=no foci,1= \<2 foci, 2=2-4 foci,3= \>4 foci; HS=more DA),NAS steatosis score 0,1,2,3; 0= \<5% hepatocytes involved (HI),1=5-33% HI ,2= 34-66% HI, 3= \>66% HI; HS=more DA. No worsening of fibrosis: no change/decrease of at least 1 stage in Brunt-Kleiner scale (BKS) compared to baseline (CTB). Improvement in fibrosis by \>=1 stage: decrease of at least 1 stage in BKS CTB. No worsening of NASH: no change/increase in NAS for ballooning, inflammation, steatosis CTB. BDRM utilized to characterize dose response across BID treatment groups, estimate posterior mean proportion (\& 90% credible interval \[CI\], indicated as 'confidence interval' below) for placebo and each BID dose studied.

Resolution of NASH: disappearance of ballooning (NAS ballooning score= 0; where 0= no ballooning, 1= few balloon cells, 2= many cells with prominent ballooning; higher scores= more disease activity), residual or no lobular inflammation (NAS lobular inflammation score 0 or 1, where 0= no foci, 1= \<2 foci, 2= 2-4 foci, 3= \>4 foci; higher scores= more disease activity), NAS steatosis score 0, 1, 2, or 3, where 0= \<5% hepatocytes involved, 1= 5-33% hepatocytes involved, 2= 34-66% hepatocytes involved, 3= \>66% hepatocytes involved; higher scores= more disease activity. No worsening of fibrosis: no change or decrease of at least 1 stage in BKS compared to baseline. Improvement in fibrosis by \>=1 stage: decrease of at least 1 stage in BKS compared to baseline. No worsening of NASH: no change or increase in NAS for ballooning, inflammation, steatosis compared to baseline.

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.