Journal
DIABETES OBESITY & METABOLISM
Volume 25, Issue 4, Pages 992-1001Publisher
WILEY
DOI: 10.1111/dom.14946
Keywords
clinical trial; fatty liver disease; liver; type 2 diabetes
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The aim of this study was to evaluate the safety, tolerability, and pharmacodynamics of the ketohexokinase inhibitor PF-06835919 in patients with NAFLD and T2D. The results showed that treatment with PF-06835919 for 16 weeks resulted in a reduction in liver fat content in patients with NAFLD and T2D, and there was no apparent dose-related trend. The 300 mg dose group had a statistically significant difference compared to the placebo group.
Aim: To assess the safety, tolerability and pharmacodynamics (PD) of the ketohexokinase inhibitor PF-06835919 in participants with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D).Materials and methods: 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 T2D on stable doses of metformin (>= 500 mg/day). Participants received once-daily placebo, PF-06835919 150 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 (co-primary endpoint) at 16 weeks, PD, safety and tolerability.Results: 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-mg and 300-mg groups, respectively (PF-06835919 300-mg group vs. placebo, P = .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.Conclusions: PF-06835919 administration over 16 weeks was generally safe and well tolerated and resulted in reductions in WLF in participants with NAFLD and T2D.
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