Extended Data Fig. 6: Clinical study designs.
a, PF-05221304 monotherapy study design, b, steps to identifying the sponsor-defined population, based on pre-qualification and Screen 1 assessments in the PF-05221304 monotherapy study, c, PF-05221304 and PF-06865571 co-administration study design. All blood samples were collected after an overnight fast of ≥8 h. In the PF-05221304 monotherapy study, samples for clinical safety-related laboratory tests were collected at pre-qualification, Screen 1 (main study screen), baseline, and at all visits throughout the treatment and follow-up periods. Samples for exploratory biomarkers, including NASH-related biomarkers, apolipoproteins, and glycemic parameters were collected at baseline and day 1 and weeks 4, 8, 12, and 16 of treatment. Samples for fasting lipid profile and HbA1c were collected at all timepoints. Non-HDL-C was derived as total cholesterol minus HDL-C, and VLDL was calculated as triglycerides/5 and reported only when triglycerides <400 mg/dL. All other parameters were measured directly. In the 1st tier stratification of the PF-05221304 monotherapy study, patients classified in the diagnosed or presumed NASH subgroup had to have a documented liver biopsy with histological evidence of NASH within 24 months of Screen 1, or meet the following criteria at pre-qualification and again at Screen 1: liver stiffness measure ≥7.0 kPa based on FibroScan® assessment; ALT > ULN and ≤5× ULN. Patients with liver stiffness measure <7.0 kPa and ALT ≤ 1.25× ULN at pre-qualification and again at Screen 1 were classified as NAFLD with likely minimal inflammation and fibrosis. aRisk factors for NAFLD/NASH: BMI of ≥25 or ≥22.5 kg/m2 in Western or Asian sites, respectively; fasting plasma glucose ≥100 mg/dL (5.6 mmol/L); fasting serum HDL-C < 40 mg/dL (1 mmol/L) or <50 mg/dL (1.3 mmol/L) for males and females, respectively; fasting serum triglycerides ≥150 mg/dL (1.7 mmol/L); seated blood pressure ≥130/85 mm Hg; waist circumference ≥40 inches (102 cm) or ≥35 inches (89 cm) for males and females, respectively; or the use of pharmacological agents with the explicit purpose of improving glycemic control, increasing HDL-C, decreasing triglycerides, or controlling blood pressure. ALT, alanine aminotransferase; BMI, body mass index; CAP, controlled attenuation parameter; HDL-C, high-density lipoprotein cholesterol; MRI–PDFF, magnetic resonance imaging-proton density fat fraction; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; PBO, placebo; PF’1304, PF-05221304 monotherapy; PF’5571, PF-06865571 monotherapy; PF’1304 + PF’5571, PF-05221304 and PF-06865571 co-administration; ULN, upper limit of normal; VLDL, very-low-density lipoprotein; wks, weeks.
