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.
Diabetes Obes Metab
; 25(4): 992-1001, 2023 04.
Article
en En
| MEDLINE
| ID: mdl-36515213
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 ANDMETHODS:
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 (111) 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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Enfermedad del Hígado Graso no Alcohólico
/
Metformina
Tipo de estudio:
Clinical_trials
Límite:
Adult
/
Humans
Idioma:
En
Revista:
Diabetes Obes Metab
Asunto de la revista:
ENDOCRINOLOGIA
/
METABOLISMO
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos