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To assess the safety, tolerability, and pharmacodynamics (PD) of ketohexokinase inhibitor PF-06835919 in participants with nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM).This double-blind, placebo-controlled, parallel-group study enrolled adults with NAFLD (≥8% whole liver fat [WLF] using MRI proton density fat fraction [MRI-PDFF]) and T2DM on stable doses of metformin ≥500 mg/day. Participants received once-daily placebo, PF-06835919 150 mg or 300 mg for 16 weeks. Randomization (1:1:1) was via an interactive response technology system. Endpoints included percentage change from baseline (CFB) in WLF using MRI-PDFF (primary endpoint) and CFB in HbA1c (coprimary endpoint) at 16 weeks, PD, safety, and tolerability.Among 164 participants randomized and treated, 145 completed the treatment (placebo n=50; PF-06835919 150 mg n=46; PF-06835919 300 mg n=49). At Week 16, least squares mean (90% confidence interval) percentage CFB in WLF was -5.26 (-12.86, 2.99), -17.05 (-24.01, -9.46), and -19.13% (-25.51, -12.20) in the placebo, PF-06835919 150-, and 300-mg groups, respectively (PF-06835919 300-mg group vs. placebo, P=0.0288). Modest numerical reductions in HbA1c were observed in all groups that did not reach statistical significance. Treatment-emergent adverse event incidence was similar across groups (40.7%, 45.5%, and 32.7% in the placebo, PF-06835919 150-mg, and 300-mg groups, respectively), with no apparent dose-related trend.PF-06835919 administration over 16 weeks was generally safe and well-tolerated and resulted in reductions in WLF in participants with NAFLD and T2DM. This article is protected by copyright. All rights reserved. |
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