Efficacy, safety and pharmacokinetics of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control.

AIMS: The objectives were to investigate the pharmacokinetics, pharmacodynamics and safety of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control, and then recommend the dosage regimen for Phase 2b/3 studies. METHODS: Three clinical studies were performed. First, 16 healthy subjects received infusion of ilaprazole 30 mg or esomeprazole 80 mg. Second, 12 healthy subjects received ilaprazole 20 mg followed by 10 mg once daily for 2 days. Finally, 20 patients with duodenal ulcers received ilaprazole 20 mg followed by 10 mg for 2 days or esomeprazole 40 mg twice daily for 3 days. Serial blood samples were collected and intragastric pH was recorded. RESULTS: The mean percentages time of intragastric pH >6 was 63.6 and 51.7% for healthy subjects after receiving ilaprazole 30 mg and esomeprazole 80 mg. Linear pharmacokinetics was observed when the dose was increased to 30 mg but the effect was saturated. Ilaprazole 20 mg followed by 10 mg for 2 days provided higher plasma exposure in healthy subjects than patients, but the effect was comparable. After multiple administrations, ilaprazole provided similar effect to esomeprazole. Ilaprazole infusion was safe and well tolerated without serious adverse events. CONCLUSIONS: Ilaprazole provided comparable effect of pH control to esomeprazole, with lower dose and fewer times of administration. There was no significant difference of ilaprazole between healthy subjects and patients regarding intragastric acid inhibition. A loading dose of ilaprazole 20 mg followed by 10 mg once daily for 2 days was recommended for Phase 2b/3 studies.

Long noncoding RNA BBOX1-AS1 increased radiotherapy sensitivity in colorectal cancer by stabilizing and activating PFK1.

PURPOSE: Our study explored the effect of long noncoding RNA BBOX1-AS1 on colorectal cancer (CRC) radiosensitivity in vivo and in vitro. METHODS: Differentially expressed lncRNAs in CRC were screened using a bioinformatics database and an online prediction website. The expression of BBOX1-AS1 in tissue samples was analyzed via real-time quantitative PCR (RT-qPCR). Subcellular localization of BBOX1-AS1 in CRC cells was analyzed using fluorescence in situ hybridization (FISH). The correlation between BBOX1-AS1 and PFK1 expression levels in CRC tissues was analyzed via Pearson's correlation coefficient. The effect of BBOX1-AS1 on PFK1 stability was investigated using RNA and protein stability testing. RNA Binding Protein Immunoprecipitation (RIP) and RNA pull-down assays were used to confirm the binding of BBOX1-AS1 to PFK1. RESULTS: BBOX1-AS1 was highly expressed in CRC and associated with poor prognosis. Similarly, it was highly expressed in CRC tissues and CRC cell lines. In addition, BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells and inhibited apoptosis. RIP and RNA pull-down experiments confirmed that BBOX1-AS1 bound to PFK1. RNA stability and protein stability experiments showed that BBOX1-AS1 affected the stability of PFK1 mRNA and protein. Furthermore, we confirmed that BBOX1-AS1 increased radiation resistance through the regulation of PFK1 expression. CONCLUSIONS: BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells through stabilization of the expression of PFK1. BBOX1-AS1 also inhibited CRC cell apoptosis and increased radiotherapy resistance in CRC cells.

Pharmacokinetic interactions between ilaprazole and clarithromycin following ilaprazole, clarithromycin and amoxicillin triple therapy.

AIM: To investigate the drug interactions between ilaprazole, a new proton pump inhibitor, and clarithromycin following ilaprazole, clarithromycin and amoxicillin combination therapy. METHODS: Twelve healthy Chinese volunteers were recruited in a randomized, open-label, 3-period crossover study. All subjects were administered ilaprazole (5 mg), clarithromycin (500 mg) or a triple therapy, including ilaprazole (5 mg), clarithromycin (500 mg) and amoxicillin (1 g), twice daily for 6 consecutive days. On the 7th day, the drugs were given once, and blood samples were collected and analyzed using a well-validated HPLC/MS/MS method. RESULTS: Following the triple therapy, the peak concentration (C(max)) and the area under the concentration-time curve from 0 h to 12 h (AUC(0→12)) of ilaprazole were significantly decreased, as compared with the single medication group (C(max):1025.0±319.6 vs 1452.3±324.6 ng/mL; AUC(0→12): 9777.7±3789.8 vs 11363.1±3442.0 ng·h/mL). Similar changes were found for ilaprazole sulfone (C(max): 5.9±0.5 vs 9.3±1.7 ng/mL; AUC(0→12): 201.4±32.1 vs 277.1±66.2 ng·h/mL). The triple therapy significantly elevated the C(max) of clarithromycin (3161.5±702.2 vs 2541.9±476.2 ng/mL). CONCLUSION: The H pylori eradication therapy with clarithromycin, amoxicillin and ilaprazole may cause pharmacokinetic interactions that decrease the amount of ilaprazole and its metabolites and elevate that of clarithromycin.

[Evaluation of the effect of ilaprazole on intragastric pH in patients with duodenal ulcer].

OBJECTIVE: To evaluate the effect of ilaprazole enteric tablets on intragastric pH in duodenal ulcer patients. METHODS: A randomized, double blind, positive controlled clinical trial was carried out. A total of forty-two patients with duodenal ulcer were randomized into low dose ilaprazole group (5 mg/d), medium dose ilaprazole group (10 mg/d), high dose ilaprazole group (20 mg/d) and omeprazole group (20 mg/d). An ambulatory 24 hour intragastric pH study was performed at the fifth treatment day. Fraction time pH above 3, 4 or 5, median values of 24 hour diurnal pH and 12 hour nocturnal pH, the percentage of patients with total time pH above 3, 4 or 5 at least for 18 hours were evaluated. RESULTS: There were no significant differences of fraction time pH above 3 or 4, median values of 24 hour diurnal pH and 12 hour nocturnal pH and the percentage of patients with total time pH above 3, 4 or 5 at least for 18 hours among all the groups with different doses of ilaprazole and the omeprazole group. The fraction time pH above 5 in medium and high dose ilaprazole groups were (87.96 + or - 12.29)% and (89.86 + or - 15.18)% respectively, which was higher than that in low dose ilaprazole group [(67.17 + or - 30.16)%] and omeprazole group [(76.14 + or - 16.75)%], P < 0.05. CONCLUSION: Ilaprazole has a strong effect on intragastric acid control with a dose dependent trend.

A randomized, double blind, controlled, multi center study of Ilaparazole in the treatment of reflux esophagitis-Phase III clinical trial.

AIM AND BACKGROUND: Proton pump inhibitors (PPIs) are the main drugs for the treatment of reflux esophagitis. Phase II clinical trials showed that, compared with Esomeprazole, the new PPI Ilaparazole is great in terms of efficacy for reflux symptoms relief and curling for esophagitis. The aim of this study was to confirm suitable dose of Ilaparazole in the treatment of reflux esophagitis. METHODS: This study used a randomized, double-blind, parallel positive drug control, multi-center design. A total of 537patients diagnosed as reflux esophagitis by gastroscopy were randomly divided into Ilaparazole group (n = 322, Ilaparazole 10 mg QD) and esomeprazole group (n = 215, Esomeprazole 40 mg QD). The patients in the two groups were treated for 8 weeks. Heartburn and reflux symptoms prior to treatment, and 2, 4 and 8 weeks after the treatment were assessed. Gastroscopy was performed after 4 weeks of treatment. Unhealed patients within 4 weeks underwent gastroscopy again at the end of 8 weeks. RESULTS: A total of 471 cases completed the treatment. In Esomeprazole and Ilaparazole groups. After 8 weeks treatment, the healing rate in Esomeprazole group and Ilaparazole group were 82.79% (94.94%) and 83.54% (92.50%), respectively. The corresponding rate difference [Ilaparazole-esomeprazole] was 0.75% (-2.44%) and the two-sided 95% CI was -5.72 to 7.22 (-6.90 to 2.01). The symptom disappearance rates for FAS (PPS) were 75.81% (82.02%) and 76.71% (80.36%) P = 0.8223 (0.7742). Adverse reactions related to the drugs were: 10.70% and 11.80%, (P = 0.7817). CONCLUSIONS: The efficacy and safety of Ilaparazole (10 mg/day) in treating reflux esophagitis was similar to esomeprazole (40 mg/day). Ilaparazole (10 mg/day) can be used in the treatment of esophagitis. The clinical trial registration number of the study is NCT 02860624.

A Randomized, Double-blind, Active-Controlled, Multi-center Study of Ilaprazole in the Treatment of Reflux Esophagitis.

BACKGROUND AND OBJECTIVE: Proton pump inhibitors (PPIs) are the main drugs for the treatment of reflux esophagitis. Previous studies have indicated ilaprazole to be safer and more effective in treating duodenal ulcers as compared with omeprazole. Being a novel PPI, ilaprazole may be used in the treatment of reflux esophagitis. The purpose of this study was to evaluate the safety and efficacy of ilaprazole tablets in the treatment of reflux esophagitis. METHODS: This study used a randomized, double-blind, multi-center, active-comparison design. The patients were randomly divided into an ilaprazole group (10 mg once daily and 15 mg once daily) and an esomeprazole group (40 mg once daily). Both the groups were treated for 8 weeks. Heartburn and reflux symptoms prior to treatment, and 4 and 8 weeks after the treatment were assessed. Gastroscopy was performed after 4 and 8 weeks. The healing rate after 4 weeks treatment was compared. If esophagitis was healed at the end of 4 weeks, patients did not undergo gastroscopy at the end of 8 weeks. RESULTS: Three hundred and twenty-five patients were enrolled in this study. The 4-week full analysis set (per-protocol set) healing rates in the esomeprazole 40-mg group, the ilaprazole 10-mg group, and the ilaprazole 15-mg group were: 71.43 % (78.89 %), 81.31 % (86.73 %), and 71.70 % (81.40 %), respectively, p = 0.1595 (0.4122); the 8-week healing rates were 84.76 % (93.33 %), 88.79 % (94.90 %), and 85.85 % (97.67 %), respectively, p = 0.6689 (0.4049). Drug-related adverse events rate were 10.48 %, 14.02 %, and 15.09 %, respectively, in the three groups (p = 0.6114). CONCLUSION: The efficacy and safety of ilaprazole (10 mg/day, 15 mg/day) in treating reflux esophagitis was similar to esomeprazole (40 mg/day). Ilaprazole (10 mg/day) has a smaller dosage, hence it should be considered more in clinical uses. TRIAL REGISTRATION: ClinicalTrials.gov NCT01107938.