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

Real-World Effectiveness of Acotiamide for Functional Dyspepsia in a South Asian Population: A Prospective Observational Study From a Tertiary Care Centre in Pakistan (ACG 2026) - "Mean age was 38.5 ± 13.7 years; 62.5% were male. Median dyspepsia duration was 26 months (IQR 14â72). At Week 8 (n = 86 for symptom follow-up), proportions with daily epigastric pain fell from 10.0% to 1.2%, and daily bloating from 21.0% to 3.5%."

Clinical • Observational data • Real-world • Real-world effectiveness • Real-world evidence • CNS Disorders • Dyspepsia • Gastrointestinal Disorder

Efficacy and Safety of Acotiamide in Functional Dyspepsia: Meta-Analysis of Randomized Controlled Trials (ACG 2026) - "Six RCTs (n â 1,697) were included. Acotiamide was more effective than placebo in improving global functional dyspepsia (FD) symptoms (RR = 1.29, 95% CI: 1.19â1.40; p < 0.00001; I² = 15%). Subgroup analysis demonstrated that efficacy significantly favored acotiamide in postprandial distress syndrome (PDS) symptoms (RR = 1.29, 95% CI: 1.09â1.53), but not in epigastric pain syndrome (EPS) (RR = 0.92, 95% CI: 0.76â1.11)."

Retrospective data • Dyspepsia • Musculoskeletal Pain

A Quantitative Symptom-Therapy Efficacy Matching Matrix for Precision Treatment Selection in Functional Dyspepsia (ACG 2026) - "Quantitative efficacy data were extracted from five RCTs that report on five different drugs - acotiamide, itopride, buspirone, lansoprazole, and nortriptyline . Matrix-guided therapy selection demonstrated superior match scores across all profiles: pure PDS (itopride 0.317, acotiamide 0.231), pure EPS (itopride 0.307, tricyclic antidepressants 0.218, proton pump inhibitors 0.212), and nausea-dominant (itopride 0.403, tricyclic antidepressants 0.264). K-means clustering confirmed Rome IV subtype separation (k=3, silhouette score 0.771). Monte Carlo validation showed model-guided responder rates exceeded empiric care by 21â28% across profiles, with simulation error < 4% versus published RCT benchmarks."

Clinical • Dyspepsia • Musculoskeletal Pain

Development and validation of an HPLC-MS/MS method for the quantification of Aficamten in human plasma and urine and application to a clinical pharmacokinetic study. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "The following MRM ion transitions were monitored: m/z 338.2 → 213.2 for CK-3773274 and m/z 343.2 → 218.2 for IS. Furthermore, critical validation parameters including matrix effects, extraction recovery, carryover, and stability were also assessed. The validated method was subsequently utilized to quantify aficamten concentrations in a clinical pharmacokinetic study involving healthy Chinese adults."

Journal • PK/PD data • Cardiomyopathy • Cardiovascular • Hypertrophic Cardiomyopathy

A Phase III Trial of Z-338 in Paediatric Patients With Functional Dyspepsia (clinicaltrials.gov) - P3 | N=55 | Completed | Sponsor: Zeria Pharmaceutical | Active, not recruiting ➔ Completed

Trial completion • Dyspepsia • Pediatrics

Metabolic reprogramming of tomato roots during rhizobacteria-mediated defense against Erwinia persicina: modulation by gold nanoparticle conjugation. (PubMed, Front Plant Sci) - "These included LC-MS/MS m/z 338.33 (putative signature 13-docosenamide or Tentative lipid amide (C22), long chain lipid-associated ions (m/z 337.06), derivatives of Benzoic acid, oleanitrile and 1H NMR peaks related to lipid, Citrate/succinate, and oxygenated compounds...Collectively, the nanoparticle-conjugated rhizobacterial treatment was associated with a metabolite profile distinct from both the pathogen-only and rhizobacteria-only treatments. This provides a preliminary metabolomic framework for understanding nano-enabled plant-microbe interactions under biotic stress."

Journal

Losartan API and Nitrosamines Impurities-Stability Profile Investigation Using HPLC, LC-MS, and In Silico Assessment. (PubMed, J Sep Sci) - "Nitrosamines are potent genotoxic impurities with well reported mutagenic and carcinogenic effects. A protective effect from nitrosamines can be also reported possibly due to their reactivity against the stressing factor. Seven degradation products were structurally proposed by LC-MS at m/z 449, m/z 447, m/z 366, m/z 338, m/z 274, m/z 391, and m/z 341, some of them predicted computationally by Zeneth."

Journal

A Phase III Trial of Z-338 in Paediatric Patients With Functional Dyspepsia (clinicaltrials.gov) - P3 | N=55 | Active, not recruiting | Sponsor: Zeria Pharmaceutical | Recruiting ➔ Active, not recruiting | N=100 ➔ 55

Enrollment change • Enrollment closed • Dyspepsia • Pediatrics

ACOTIAMIDE INDUCED BIDIRECTIONAL VENTRICULAR TACHYCARDIA IN A PATIENT WITH DILATED CARDIOMYOPATHY (ACC 2026) - "Background: Bidirectional ventricular tachycardia (BVT) is rare, typically linked to digoxin toxicity or catecholaminergic polymorphic VT. This case highlights a novel presentation of acotiamide-induced BVT in structural heart disease. Vigilant review of medication history is essential in unexplained ventricular arrhythmias"

Clinical • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Infectious Disease • Metabolic Disorders • Ventricular Tachycardia

Comparing Acotiamide and Itopride for the Management of Indigestion (clinicaltrials.gov) - P4 | N=368 | Not yet recruiting | Sponsor: Aga Khan University

Head-to-Head • New P4 trial • Dyspepsia

Efficacy and safety of acotiamide in esophagogastric junction outflow obstruction: a placebo-controlled phase II trial. (PubMed, Esophagus) - "Acotiamide is effective in normalizing impaired LES relaxation in patients with EGJOO and may improve food-sticking symptoms in the chest."

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

Development and Validation of a Rapid LC-MS/MS Method for the Quantification of Contezolid in Human Plasma and Liver, and Its Application to a Pharmacokinetic Study in Liver Transplant Patients. (PubMed, Biomed Chromatogr) - "Quantification was performed in multiple reaction monitoring (MRM) mode, monitoring the transitions m/z 409.1 → 269.1 for contezolid and m/z 338.1 → 296.2 for linezolid...The validated assay was successfully applied to a pharmacokinetic study of contezolid in liver transplant recipients. In conclusion, this robust, efficient, and cost-effective LC-MS/MS method provides a valuable tool for the determination of contezolid in clinical and pharmacokinetic research."

Journal • PK/PD data • Transplantation

LC-MS/MS Method for Simultaneous Quantification of Three Oxazolidinone Antimicrobials in Human Plasma: Application to Therapeutic Drug Monitoring. (PubMed, Drug Des Devel Ther) - "Detection was performed via positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode, targeting transitions: m/z 338.14→162.8 (linezolid); m/z 371→343.1 (tedizolid) and m/z 409.15→269.14 (contezolid), with voriconazole-d3 as the internal standard. This method has been successfully applied to monitor the concentrations of both drugs during the transition between linezolid and contezolid therapy. This validated LC-MS/MS method enables the simultaneous determination of linezolid, tedizolid, and contezolid in human plasma, rendering it promising for pharmacokinetic studies and TDM, and contributing to optimized patient care in complex therapeutic scenarios."

Journal • Infectious Disease

Acotiamide vs Itopride in Postprandial Distress Syndrome (clinicaltrials.gov) - P3 | N=152 | Not yet recruiting | Sponsor: Getz Pharma

New P3 trial • Dyspepsia

Quantitation by liquid chromatography-nanoelectrospray ionization-high resolution tandem mass spectrometry of DNA adducts in oral cells of smokeless tobacco users (ACS-Fall 2025) - P=N/A | "The eluents containing the adducts were dried, redissolved in 20 µl H2O, and analyzed by LC-NSI-HRMS/MS with selected reaction monitoring for specific transitions based on our preliminary data: 3-Me-Ade from a methylating agent, possibly NNK in tobacco, m/z 150 [M + H]+ → 123.0665; 7-Et-Gua from an ethylating agent in tobacco, m/z 180 [M + H]+ → 152.0565; gamma-OH-Acr-dG (from acrolein), m/z 324 [M + H]+ → 208.0829 [BH]+; gamma-OH-Cro-dG (from crotonaldehyde or acetaldehyde) m/z 338 [M + H]+ → 222.0986 [BH]+; and 8-oxo-dG (from oxidative damage) m/z 284 [M + H]+ →168.0511 [BH]+; with a mass tolerance of 5 ppm...Adduct levels except 8-oxo-dG were 4 - 87 times higher than in non-smokers. The results of this study provide new insights on DNA damage in the oral mucosa of users of smokeless tobacco, a known cause of oral cavity cancer."

Oral Cancer

Efficacy of Acotiamide in Pediatric Patients with Functional Dyspepsia. (PubMed, Pediatr Gastroenterol Hepatol Nutr) - "Acotiamide demonstrated efficacy in pediatric FD, which is consistent with previously reported outcomes in adults. Acotiamide may be a beneficial treatment option for pediatric FD across all subtypes."

Journal • Dyspepsia • Musculoskeletal Pain • Pain • Pediatrics

Novel LC-MS/MS Method for Quantification of Famotidine and Metoprolol and Application to Pharmacokinetic Interaction. (PubMed, Biomed Chromatogr) - "The monitored transitions were m/z 338.1 → 189.1 for FAM, 268.2 → 116.1 for MET, 342.1 → 190 for D4-FAM, and 274.2 → 122.1 for D6-MET. The validated method was verified to meet the determination requirements of biological samples. It was the first time to study the pharmacokinetics interaction between FAM and MET successfully, which would be necessary and beneficial to explore the clinical safety and efficacy of the combination of these two drugs in the treatment of HF."

Journal • PK/PD data

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