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Journal of Hepatology ; 77:S14, 2022.
Article in English | EMBASE | ID: covidwho-1967492


Background and aims: Approval of a drug therapy for NASH requires a very good safety/tolerability profile and acceptable therapeutic index. MAESTRO-NAFLD-1 (NCT04197479) is a randomized doubleblind (DB) Phase 3 clinical trial of placebo (PBO) versus resmetirom (RES), a once-a-day oral selective thyroid hormone receptor β agonist, in >1100 patients with NAFLD with safety as the primary end point. Method: Enrollment was Dec 2019 to Oct 2020 at 79 US sites. Requirements included 3 metabolic risk factors, fibroscan (FS) ≥5.5 kPa/CAP≥280 dBm, MRI-PDFF≥8%. Randomization was 1:1:1:1 to 3 DB arms, PBO, 80 or 100 mg RES (n = 972) or an 100 mg open label (OL) arm (n = 171). The primary objective was to evaluate the safety and tolerability of 80 or 100 mg RES versus PBO measured by the incidence of adverse events (AEs). Results: At baseline the DB safety population (n = 969) was age 55.9 (11.8);female, 54.4%, white 88.6%;hispanic 34.7%;BMI 35.3 (6.0) type 2 diabetes 49%, hypertension 76.1%, dyslipidemia 87.9%;FS 7.4 (4.7) kPa. Discontinuations (22.5%) did not differ by treatment, most patient decision (pandemic related). DB compliancewas impacted by COVID drug kit delays. AE withdrawals were 80 mg, 2.4%;100 mg, 2.8%;PBO, 1.3%. The primary objective was met. TEAEs were 80 mg, 88.4%;100 mg, 86.1%;PBO, 81.8%. TEAEs ≥grade 3 severity were 80 mg, 7.6%;100 mg, 9.0%;PBO, 9.1%. AEs in excess of PBOwere grade 1–2 AEs of diarrhea (80 mg, 23.5%;100 mg, 31.2%;PBO, 13.8%) and nausea (80 mg, 11.9%;100 mg, 18.2%;PBO, 7.9%), in the first few weeks. ALT increases ≥3XULN were 80 mg, 0.61%;100 mg, 0.31%;PBO,1.6%. Therewere no changes in bodyweight or HR. BP decreased by 2–3 mmHg in the RES arms. Key 2o end points were met (Table). Comparative mean reduction in FS VCTE was not significant;a responder analysis of FS and MRE showed significant reductions with RES treatment. Conclusion: RES achieved the primary safety end point in this 52- week Phase 3 NAFLD clinical trial that identified patients by metabolic risk and non-invasive imaging. Key 2o end points were met including LDL-C, ApoB, triglycerides, MRI-PDFF, FS (CAP).(Table Presented) 1MRE combined RES groups.

Hepatology ; 74(SUPPL 1):341A-342A, 2021.
Article in English | EMBASE | ID: covidwho-1508738


Background: The COVID19 pandemic has affected persons dietary habits and life style, with effects on body weight. We have assessed the effect of the pandemic on the liver health by quantifying the changes in liver enzymes, hepatic steatosis and fibrosis in patients with chronic liver disease. Methods: This is a multi-center US study that included 3 tertiary clinical centers. Patients with chronic liver disease (51 NAFLD, 8 with resolved hepatitis C, 3 chronic hepatitis B, 5 primary biliary cholangitis and 36 combination of chronic liver disease), without evidence of an acute process (e.g. alcoholic hepatitis, alcohol abuse or new decompensation of cirrhosis), were enrolled. Patients were assessed between January and March 2020 and January and March 2021. Assessment included laboratory tests and controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) on vibration transient elastography (VCTE). Results: 103 patients were assessed twice during the two periods. Baseline mean alanine aminotransferase (ALT) was 37 ± 36 (SD) U/L;aspartate aminotransferase (AST) 30 ± 18 U/L;total bilirubin 0.6 ± 0.31 mg/dL;albumin, 4.2 ± 0.72 g/dL;CAP score 293 ± 70 dB/m;and LSM on VCTE 8.1 ±6.2 kPa. Weight gain occurred in 54% of the population, whereas 39% lost weight, and 7% had no weight change. LSM increased by >20% in 30% of subjects;decreased by 20% in 27%;and remained within the 20% range in 43%. LSM increase by 20% was associated with significant weight gain and ALT increase (+2.3 ± 6.5 kg, and +17 ± 49.U/L (p<0.05)), in comparison to subjects who had their LSM changes within 20% range (+1.1 (3.7) kg, and -5.3 ±22.0 U/L) or had >20% decrease in LSM (-0.3 ±5.8 kg, and -6.0 ±21 U/L). CAP score median change was -2.9 ±85 dB/m in those who had LSM increase by >20%, whereas the score changed by 0.0 ± 44 dB/m in those who had LSM changes within 20% or 1.0 ± 58 dB/m in those >20% decrease. Conclusion: During the COVID 19 pandemic in this U.S. population, more than half of subjects with chronic liver disease gained weight, but others had no change or decreased weight. Adverse liver changes (LSM>20% and increased ALT) occurred in one-third of the population.