Cinitapride in the Treatment of Functional Dyspepsia – An Overview and Meta-Analysis of Current Data

Direct Comparison of Cinitapride and Domperidone
One type of functional dyspepsia (FD) is postprandial distress syndrome (PDS), which is characterized primarily by an unpleasant sensation of fullness after meals and early satiety. The efficacy of cinitapride in this indication was assessed in a multicenter, double-blind, randomized phase III clinical trial involving 383 patients with mild to moderate dyspeptic symptoms diagnosed as FD based on gastroscopy, abdominal ultrasound, and laboratory findings.

Randomized Double-Blind Study
Patients were randomized to receive cinitapride (1 mg) or domperidone (10 mg) three times daily before meals for 28 days. The primary endpoint was the non-inferiority of cinitapride in terms of symptom relief. Secondary objectives included effects on gastric emptying and overall patient assessment of treatment.

Greater Relief from Fullness with Cinitapride
After four weeks, symptom relief rates did not differ significantly, with 85.8% of patients on cinitapride and 81.8% on domperidone achieving relief (p = 0.332). Cinitapride significantly reduced the severity of postprandial fullness, early satiety, and bloating (p < 0.001), performing better than domperidone in these aspects (p = 0.021 for direct comparison). Cinitapride also shortened the mean gastric emptying half-time from 131 to 89 minutes (p = 0.0002). A positive correlation was observed between symptom improvement and gastric emptying time.
Adverse events (AEs) potentially related to cinitapride treatment occurred in 8.4% of cases, compared to 9.9% in the domperidone arm. Only one patient experienced extrapyramidal symptoms, while other AEs included transient symptoms or abnormal laboratory findings.

Cinitapride and Other Prokinetics
A network meta-analysis published last year in BMC Gastroenterology indirectly compared the efficacy of various prokinetics, including cinitapride.

Network Meta-Analysis of Prokinetics Studies
Randomized controlled trials of prokinetics (metoclopramide, mosapride, domperidone, itopride, acotiamide, cinitapride) in adults with FD published up to March 2023 were identified through PubMed, EMBASE, the Cochrane Library, and Web of Science. A Bayesian network meta-analysis was conducted, with the primary endpoint being overall efficacy (expressed as odds ratios [OR] relative to the control group) and the secondary endpoint being the incidence of adverse events.

Highest Efficacy for Metoclopramide and Cinitapride
The analysis included 28 studies with a total of 5,790 participants (individual studies included 16–892 subjects). Most participants (n = 5,510) were diagnosed with FD, while 280 specifically had PDS as an FD subtype.
The meta-analysis showed that metoclopramide had higher overall efficacy compared to mosapride (OR 3.53; 95% confidence interval [CI] 1.70–7.47), domperidone (OR 2.29; 95% CI 1.16–4.63), itopride (OR 2.77; 95% CI 1.41–5.59), acotiamide (OR 2.63; 95% CI 1.33–5.36), and placebo (OR 5.68; 95% CI 2.98–11.10). The efficacy of metoclopramide was comparable to that of cinitapride (OR 1.62; 95% CI 0.75–3.53), which demonstrated higher efficacy than mosapride (OR 2.18; 95% CI 1.16–4.14) and placebo (OR 3.52; 95% CI 2.01–6.24).
The efficacy of individual prokinetics compared to placebo is summarized in the figure below. However, the number of participants in the groups was significantly heterogeneous.
Cinitapride exhibited a lower overall risk of adverse events than domperidone. No differences were observed between prokinetics in the frequency of adverse events related to medication use.

Conclusion
The phase III study confirmed the non-inferiority of cinitapride compared to domperidone in patients with mild to moderate FD predominantly exhibiting PDS symptoms. According to the current meta-analysis, cinitapride and metoclopramide may demonstrate better efficacy than other prokinetics in treating FD. Cinitapride also likely has a lower risk of adverse events.

References:

1. Du Y., Su T., Song X. et al. Efficacy and safety of cinitapride in the treatment of mild to moderate postprandial distress syndrome–predominant functional dyspepsia. J Clin Gastroenterol 2014; 48: 328–335, doi: 10.1097/MCG.0000000000000033.
2. Qi Q., Wang N., Liu H., Li Y. Prokinetics for the treatment of functional dyspepsia: an updated systematic review and network meta-analysis. BMC Gastroenterol 2023; 23 (1): 370, doi: 10.1186/s12876-023-03014-9.
3. SPC Gapulsid. Available at: https://prehledy.sukl.cz/prehledy/v1/dokumenty/63568