Objective:

2

To assess the efficacy and safety profile of

Aurantii Fructus Immaturus

flavonoid (AFIF) tablets in the treatment of patients with functional dyspepsia (FD).

Methods:

2

In this phase Ⅲ

randomized

controlled clinical trial

participants diagnosed with FD from 7 medical centers across China were assigned by stratified block randomization to either AFIF treatment group (3 AFIF tablets

0.29 g per tablet) or placebo group on the same schedule in a 3:1 ratio. The primary endpoint was the complete disappearance of 4 core FD symptoms

including postprandial fullness

early satiety

upper abdominal pain

and upper abdominal burning

following a 4-week treatment regimen (3 times daily). Secondary endpoints included the individual symptom disappearance rates and gastric emptying function after 4 weeks

as well as the disappearance rates for all 4 individual symptoms of FD at 4 weeks after treatment. Subgroup analyses included 3 clinical symptoms and 4 Chinese medicine patterns. Safety assessments included monitoring treatment-emergent adverse events (AEs)

serious adverse events (SAEs)

intervention-related AEs

and any AEs leading to discontinuation.

Results:

2

Of the enrolled patients

299 in the AFIF gr

oup and 99 in the control group were induded in the full analysis set (FAS) and safety set (SS). After 4 weeks of treatment

the complete disappearance of all 4 core FD symptoms was achieved in 31.44% (94 cases) of patients in the AFIF group compared to 6.06% (6 cases) in the placebo group (

P

<

0.01). At 4 weeks after end of treatment

the rates of symptom disappearance were 23.43% (67 cases) in the AFIF group and 2.22% (2 cases) in the placebo group (

P

<

0.01). Individual symptom disappearance rates were significantly higher in the AFIF group at both week 4 and 4 weeks after treatment (all

P

<

0.01). Additionally

the patients in the AFIF group exhibited a significantly greater improvement in gastric emptying at 2 h post-meal [66.55% (50.03

84.55)

]

compared to the placebo group [51.10% (44.75

68.93)

P

= 0.027

]

. At weeks 4 and 4 weeks after treatment

in the FAS

the disappearance rates of all 4 core FD symptoms remained higher in the AFIF group compared to the placebo group (all

P

<

0.05). The per protocol set results similarly aligned with those observed in the FAS. Intervention-related AEs were reported in 6.02% (18 cases) of the AFIF group and 8.08% (8 cases) in the placebo group

with no SAEs recorded in either group. The patients in the AFIF group showed significantly higher complete symptom resolution rates of all 4 core FD symptoms at 4 weeks and 4 weeks after treatment across most subgroups

compared to the placebo group (all

P

<

0.05). All AEs related to AFIF Tablets were mild.

Conclusion:

2

AFIF tablets demonstrated robust efficacy in alleviating the symptoms of FD

with a favorable safety profile. (Registration No. CTR20132482)