Efficacy and Safety of Aurantii Fructus Immaturus Flavonoid Tablets in Patients with Functional Dyspepsia: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial.

OBJECTIVE

To assess the efficacy and safety profile of Aurantii Fructus Immaturus flavonoid (AFIF) tablets in the treatment of patients with functional dyspepsia (FD).

METHODS

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

Of the enrolled patients, 299 in the AFIF group 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

AFIF tablets demonstrated robust efficacy in alleviating the symptoms of FD, with a favorable safety profile. (Registration No. CTR20132482).