A phase 2a, randomized, double-blind, placebo-controlled, three-arm, parallel-group study to assess the efficacy, safety, tolerability and pharmacodynamics of PF-06835919 in patients with non-alcoholic fatty liver disease and type 2 diabetes.

Abstract

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.

• Authors: Aditi R Saxena, Stephanie-An Lyle, Kaivan Khavandi, Ruolun Qiu, Mark Whitlock, William P Esler, Albert M Kim
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 25 Issue 4 Pg. 992-1001 (04 2023) ISSN: 1463-1326 [Electronic] England
• PMID: 36515213 (Publication Type: Randomized Controlled Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022 Pfizer, Inc. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Chemical References

• Glycated Hemoglobin
• Metformin

Topics

• Adult
• Humans
• Diabetes Mellitus, Type 2 (drug therapy)
• Non-alcoholic Fatty Liver Disease (drug therapy)
• Glycated Hemoglobin
• Metformin (therapeutic use)
• Double-Blind Method
• Treatment Outcome