Acofide (acotiamide) / Zeria Pharma, Astellas - LARVOL DELTA

EVALUATING THE EFFICACY AND SAFETY OF ACOTIAMIDE IN PATIENTS WITH ESOPHAGOGASTRIC JUNCTION OUTFLOW OBSTRUCTION: AN INVESTIGATOR-INITIATED, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE II TRIAL (DDW 2025) - "Acotiamide is effective for normalizing impaired LES relaxation in EGJOO patients and may improve food sticking symptoms in the chest, thereby enhancing the quality of life."

Clinical • P2 data • Gastrointestinal Disorder

Effect of Acotiamide on Detrusor Underactivity Induced Through Bilateral Pelvic Nerve Crush Injury in Rats. (PubMed, Int Neurourol J) - "Acotiamide showed effectiveness in the treatment of underactive bladder, possibly through activation of bladder afferent and detrusor activities."

Journal • Preclinical • Urology

LC-MS/MS Methods for Quantification of Topiramate and Degradant in a Novel Intravenous Formulation and in Biological Matrices: Applications in Drug Development and Toxicokinetic Studies (AES 2024) - "Detection was performed using multiple reaction monitoring (MRM) with a Waters Xevo TQ-S mass spectrometer, targeting topiramate (m/z 338 → 78); its internal standard (IS), D12-topiramate (m/z 350 → 78); and potential metabolite, 4,5-desisopropylidene topiramate (m/z 298 → 78). The LC-MS/MS methods offer reliable and precise quantification of topiramate and its potential degradants and metabolites in the formulation and in biological matrices. The methods enable manufacturing of the topiramate formulation, and pharmacokinetic and toxicokinetic studies. The observed sex differences in topiramate pharmacokinetics in rats highlights the importance of considering gender in dosing of topiramate, particularly when used in critical conditions like seizure emergencies."

CNS Disorders • Epilepsy

Effective Management of Chronic Intestinal Pseudo-Obstruction in MELAS Using Acotiamide: A Case Report. (PubMed, Case Rep Neurol) - "A stroke-like episode of MELAS was suspected and combined therapy with arginine, edaravone, and levetiracetam was initiated. Patients with MELAS could possibly experience stroke-like episodes during CIPO. Since acetylcholine possibly plays an important role in the pathophysiology of CIPO and acotiamide possesses prokinetic activity by inhibiting acetylcholinesterase, acotiamide could possibly improve CIPO symptoms."

Journal • Anorexia • Cardiovascular • CNS Disorders • Metabolic Disorders • Pain

Long-Term Vonoprazan and Acotiamide-Refractory Patients With Functional Dyspepsia Partly Exhibit Pancreatic Enzyme Abnormalities. (PubMed, Cureus) - "Long-term vonoprazan alone or vonoprazan and acotiamide combination therapy significantly improved each FD symptom. The OTE in patients treated with vonoprazan alone or vonoprazan and acotiamide combination therapy was only 50%. Long-term vonoprazan and acotiamide combination therapy may differentiate patients with pancreatic enzyme abnormalities from those with FD."

Journal • Dyspepsia

Is It Possible to Regenerate the Underactive Detrusor? Part 1 Molecular and Stem Cell Therapies Targeting the Urinary Bladder and Neural Axis ICI-RS 2024. (PubMed, Neurourol Urodyn) - "Several options are currently being pursued in the search for an elusive molecular or stem cell option for enhancing the power of the detrusor muscle. These encompass a wide range of approaches that target each aspect of the contraction mechanism including the urothelium of bladder and urethra, myocyte, and neural pathways. While none of these have shown unequivocal clinical utility, some appear promising. Lessons from other fields of medicine might prove instructive."

Journal • Review • Urology • GRP-10

A Phase III Trial of Z-338 in Paediatric Patients With Functional Dyspepsia (clinicaltrials.gov) - P3 | N=100 | Recruiting | Sponsor: Zeria Pharmaceutical | Trial completion date: Apr 2025 ➔ Jun 2026 | Trial primary completion date: Feb 2025 ➔ Mar 2026

Trial completion date • Trial primary completion date • Dyspepsia • Pediatrics

Amine-containing donepezil analogues as potent acetylcholinesterase inhibitors with increased polarity. (PubMed, RSC Med Chem) - "Peripheral acetylcholinesterase (AChE) inhibitors such as acotiamide have shown efficacy in FD treatment, but their limited affinity towards the enzyme has hindered their effectiveness. The compounds show low membrane permeability, which indicates a significantly reduced central activity. These findings suggest that the developed inhibitors could potentially serve as promising treatments for functional dyspepsia."

Journal • Alzheimer's Disease • CNS Disorders • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Pain

Current status and prospects of using the prokinetic acotiamide in gastroenterology: A review (PubMed, Ter Arkh) - "Currently, the clinical efficacy of acotiamide in the population of patients with functional dyspepsia is demonstrated in more than 10 clinical studies in different regions of the world, demonstrating a reduction of the symptoms of the disease during treatment with this agent and an improvement in the quality of life of patients. In addition, the combination of acotiamide with proton pump inhibitors optimizes the management of patients with gastroesophageal reflux disease."

Journal • Review • Dyspepsia • Gastroenterology • Gastroesophageal Reflux Disease • Gastrointestinal Disorder

Prokinetics for the treatment of functional dyspepsia: an updated systematic review and network meta-analysis. (PubMed, BMC Gastroenterol) - "Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed."

Clinical • Journal • Retrospective data • Review • Dyspepsia

Evaluating the efficacy and safety of acotiamide in patients with esophagogastric junction outflow obstruction: study protocol for an investigator-initiated, multi-center, randomized, double-blind, placebo-controlled phase II trial. (PubMed, Trials) - "This trial will provide evidence to clarify the efficacy and safety of acotiamide as a treatment for patients with EGJOO. Acotiamide might help improve the quality of life of patients with EGJOO and is expected to prevent the progression of EGJOO to achalasia."

Clinical • Journal • P2 data • Gastrointestinal Disorder • Rare Diseases

Vonoprazan Therapy is as Effective for Functional Dyspepsia without Heartburn as Acotiamide Therapy. (PubMed, J Gastrointestin Liver Dis) - "These preliminary results suggest that vonoprazan is effective for the treatment of functional dyspepsia without heartburn in the short-term, with results similar to acotiamide therapy."

Journal • Retrospective data • Constipation • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Pain

The Effect of Acotiamide on Nausea as a Symptom of Chronic Nausea and Vomiting Syndrome after Coronavirus Disease 2019: A Case Report. (PubMed, Intern Med) - "The patients' symptoms responded quickly to acotiamide, a medication that is effective for treating functional dyspepsia (FD). Despite being a distinct illness from FD, CNVS is also a functional gastrointestinal disorder, and acotiamide may be just as effective for CNVS following COVID-19 as for FD."

Journal • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

YM443 in Subjects With Functional Dyspepsia (clinicaltrials.gov) - P2b; N=416; Completed; Sponsor: Astellas Pharma Inc; Phase classification: P2 ➔ P2b

Phase classification • Biosimilar

Quantitation of acrolein and crotonaldehyde-derived DNA adducts in oral brushings from smokers and nonsmokers using liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry | Poster Board #3333 (ACS-Fall 2022) - "The eluents containing the adducts were dried, redissolved in 20 l H2O, and analyzed by LC-NSI-HRMS/MS with selected reaction monitoring of m/z 324 [M+H]+ →208.0829 [BH]+ and m/z 338 [M+H]+ → m/z 222.0986 [BH]+, respectively, with a mass tolerance of 5 ppm...The differences in both DNA adducts between smokers and non-smokers are statistically significant (p<0.001). Our results demonstrate that oral cells are excellent sources of material for evaluating DNA adducts as biomarkers of tobacco smoke exposure and biomolecular changes potentially related to the development of cancer."

Oncology

Application of Different UV Spectrophotometric Methods for Quantitative Analysis of Acotiamide and Esomeprazole. (PubMed, J AOAC Int) - "The proposed methods were succeeded to quantify acotiamide and esomeprazole in the synthetic mixtures and in their pharmaceutical tablets without any interference from each other or from tablet additives. Simple and validated UV spectrophotometric methods were described for selective quantification of the acotiamide and esomeprazole in their mixture."

Journal • Gastroenterology • Gastrointestinal Disorder

Evidence-based clinical practice guidelines for functional dyspepsia 2021. (PubMed, J Gastroenterol) - "These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD."

Clinical guideline • Journal • Review • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Mood Disorders • Pain • Psychiatry

Acotiamide and Functional Dyspepsia: A Systematic Review and Meta-Analysis. (PubMed, Cureus) - "Acotiamide seems to be a promising agent in functional dyspepsia. However, further larger studies are needed to evaluate the role of acotiamide in functional dyspepsia."

Journal • Retrospective data • Review • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Pain

Determination of Valproic Acid Distribution and Absolute Quantification in Brain by MALDI MSI Following Continuous Intracerebroventricular Infusion (AES 2021) - "For the detection of VPA and its metabolites, mass spectra were acquired in positive mode with a Continuous Accumulation of Selected Ions (CASI) mode of acquisition within m/z 338 to 358 Da range and a spatial resolution of 100 µm. MSI helped better understand the distribution of VPA, its metabolites, and the impact of these on GABA concentrations in different regions of the brain. One effect of ICV infusion of sodium valproate in male rat brains is an increase in GABA."

CNS Disorders • Epilepsy

Use of Acotiamide in Functional Dyspepsia: A Systematic Review and Meta-Analysis (ACG 2021) - "Three studies were included in quantitative synthesis. Improvement in symptoms of functional dyspepsia after treatment was higher in the treatment group compared to placebo but could not reach statistical significance in random effect model (OR, 1.48; 95% CI, 0.93 to 2.35; n = 1697; I2 = 59%). No significant differences in adverse effects were reported between two groups for raise in serum prolactin (OR 1.02, 95% CI 0.64 to 1.61; n = 1709; I2 = 44%), raise in ALT (OR 1.27, 95% CI 0.70 to 2.33; n = 1709; I2 = 0%), raise in serum bilirubin (OR, 0.98; 95% CI, 0.52 to 1.87; I 2 = 0%)."

Retrospective data • Review • Dyspepsia

Efficacy and Safety of Acotiamide Versus Mosapride in Patients With Functional Dyspepsia Associated With Meal-Induced Postprandial Distress Syndrome: A Phase III Randomized Clinical Trial. (PubMed, Cureus) - " Our study results demonstrated that Acotiamide is effective, safe, and well-tolerated and had significantly improved the QoL over a four-week treatment period in FD-PDS patients. The efficacy and safety profiles of Acotiamide were similar to Mosapride."

Clinical • Journal • P3 data • Dyspepsia • Musculoskeletal Pain • Pain

The treatment effects of acotiamide in esophagogastric outflow obstruction: a prospective longitudinal observational study. (PubMed, Esophagus) - "Acotiamide has a treatment effect on patients with EGJOO via a reduction in the IRP level through the lowering of both the basal LES pressure and LES accommodation response. Dysphagia is a key symptom to be evaluated and treated in patients with EGJOO."

Clinical • Journal • Observational data • Dyspepsia • Gastrointestinal Disorder

[VIRTUAL] Overlap Cluster 1: Dyspepsia and GERD (APDW 2021) - "The putative pathophysiology of this FD-GERD overlap may include impaired gastric accommodation with transient lower esophageal sphincter relaxations (TLESRs), duodenal eosinophilia and duodenal hypersensitivity. Then, possible treatment options may include histamine H1/H2 receptor blockade, anti-secretory agents such as PPI or P-CAB, neuromodulators such as tricyclic agent and fundus relaxant such as baclofen, acotiamide, etc."

Dyspepsia • Eosinophilia • Gastroenterology • Gastroesophageal Reflux Disease • Immunology

Efficacy of acotiamide on postprandial distress syndrome and epigastric pain syndrome depending on the estimated gastric acid secretion level. (PubMed, J Neurogastroenterol Motil) - "While the response rates were stable, ranging from 61.0% to 75.0% regardless of the estimated gastric acid secretion level among PDS subjects, the rates were significantly lower in hyper-secretors than in non-hyper-secretors among EPS subjects (42.0% vs 83.0%, P = 0.046). Although acotiamide is effective for treating EPS as well as PDS overall, the efficacy is somewhat limited in EPS with gastric acid hyper-secretion, with gastric acid suppressants, such as proton pump inhibitors, being more suitable."

Clinical • Journal • Dyspepsia • Infectious Disease • Musculoskeletal Pain • Pain

Gastric accommodation: Physiology, diagnostic modalities, clinical relevance, and therapies. (PubMed, Neurogastroenterol Motil) - "Several treatment options including sumatriptan, buspirone, tandospirone, ondansetron, and acotiamide may improve symptoms by increasing post-meal gastric volume. There are an increasing number of gastric accommodation testing modalities; however, each has facets which warrant consideration. Evidence regarding potentially effective therapies for IFA is growing."

Clinical • Journal • Review • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • MRI