Zydena (udenafil) / Mezzion - LARVOL DELTA

FUELExten: A Extension Study of Udenafil in Adolescents (clinicaltrials.gov) - P3 | N=301 | Completed | Sponsor: Mezzion Pharma Co. Ltd | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Heart Failure

FALD: Evaluation of Fontan-associated Hepatic Stiffness and the Efficacy of Udenafil in Reducing Liver Stiffness (clinicaltrials.gov) - P3 | N=88 | Completed | Sponsor: Mezzion Pharma Co. Ltd | Phase classification: P ➔ P3

Biomarker • Phase classification • Cardiovascular • Heart Failure

Pharmacological Modulation of Liver and Spleen Stiffness in a Cirrhotic Rat Model. (PubMed, Hepat Med) - "Rats were divided into six groups: control (sodium chloride), metoprolol, udenafil, enalapril, terlipressin, and carvedilol. Terlipressin did not reduce LS or SS, likely due to opposing effects of increased MAP and reduced PVP. In conclusion, combined LS and SS measurements may provide valuable non-invasive insights into patient responses and adherence to PH-lowering therapies."

Journal • Preclinical • Cardiovascular • Fibrosis • Hypertension • Immunology • Liver Cirrhosis • Portal Hypertension

Revisiting the Effect of Udenafil on Exercise Performance in Patients With Fontan Circulation: Results of a Post Hoc Analysis of the FUEL Trial. (PubMed, J Am Heart Assoc) - "In this post hoc subgroup analysis, after exclusion of patients with Fontan circulation with near-normal baseline peak Vo2, a positive treatment effect of udenafil was identified for the primary outcome of peak Vo2. The interaction between baseline peak Vo2 and treatment may have influenced the outcome of the FUEL trial."

Journal • Retrospective data

Parental and adolescent perceptions of clinical trial participation: the FUEL randomised controlled trial and open-label extension study. (PubMed, Cardiol Young) - "Perceptions of research were positive and slightly better for parents. Study teams and compensation were key contributors to positive perceptions. Study burden and testing were viewed less favourably. Future studies should consider families' preferences and potential barriers to participation."

Journal • Cardiovascular • Heart Failure

FALD: Evaluation of Fontan-Associated Liver Disease (clinicaltrials.gov) - P=N/A | N=88 | Completed | Sponsor: Mezzion Pharma Co. Ltd | Active, not recruiting ➔ Completed

Biomarker • Trial completion • Cardiovascular • Heart Failure • Hepatology

Methylated Arginine Metabolites as Biomarkers for Clinical Status and Response to Type 5 Phosphodiesterase Inhibition in Patients With Fontan Circulation. (PubMed, J Am Heart Assoc) - "Plasma concentrations of metabolites that inhibit NO flux are associated with negative clinical outcomes and worse exercise capacity. Moreover, metabolite shifts over time associated with increased NO flux are associated with improved exercise capacity. In patients with a Fontan circulation, the NO pathway modulators ADMA and symmetric dimethyl arginine may be useful as biomarkers of clinical status and predictive of response to PDE5is."

Biomarker • Journal • Cardiovascular • Heart Failure

New and Emerging Therapeutic Drugs for the Treatment of Pulmonary Arterial Hypertension: A Systematic Review. (PubMed, Cureus) - "Several FDA-approved therapeutic options are available, including prostacyclin analogs (epoprostenol, iloprost, and treprostinil), the non-prostanoid IP receptor agonist selexipag, selective endothelin receptor antagonists (ERA) (ambrisentan, bosentan, and macitentan), phosphodiesterase 5 inhibitors (sildenafil and tadalafil), and the soluble guanylate cyclase (sGC) stimulator riociguat...The review found that while udenafil, imatinib, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were evaluated, imatinib was notably associated with adverse side effects. Conversely, udenafil, racecadotril, sotatercept, anastrozole, riociguat, tacrolimus, and ralinepag were found to be safe, well-tolerated, and effective in improving hemodynamic measures and 6-MWDs. This study aims to summarize the developing treatment options currently under clinical trials, highlighting the need for further trials before their application in clinical practice."

Journal • Review • Cardiovascular • Fibrosis • Hypertension • Immunology • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

An overview of conventional and investigational phosphodiesterase 5 inhibitors for treating erectile dysfunction and other conditions. (PubMed, Expert Opin Investig Drugs) - "Pre-clinical and early clinical trials that investigated safety, efficacy and tolerability of novel PDE5I such as Udenafil, Mirodenafil, Lodenafil, Youkenafil, Celecoxib and TPN729 in treatment of ED and other conditions. Preclinical and limited early clinical studies of the new molecules of PDE5I have demonstrated encouraging results however, safety, efficacy, and tolerability are still an issue that necessitate further long-term multicenter clinical studies to ensure justification of their uses in treatment of ED and other conditions.Progress in molecular delivery techniques and tailored patient-specific management and additional therapeutic technology will dramatically improve care for ED and other conditions. The dream of ED and many other conditions becoming more effectively managed may be feasible in the near future."

Journal • Review • Erectile Dysfunction

Nicolau syndrome (embolia cutis medicamentosa) due to glatiramer acetate (Copaxone) injection: a case report (BAD 2024) - "Drug history included glatiramer acetate, levothyroxine, pregabalin, udenafil, propranolol, levetiracetam and docusate...Oral doxycycline 100 mg once daily was started, as a swab showed a heavy growth of Staphylococcus aureus...Conservative treatment with debridement, pain control and dressings are the mainstays of therapy. This case highlights the need for awareness about this rare condition."

Case report • Clinical • Anesthesia • CNS Disorders • Epilepsy • Immunology • Multiple Sclerosis • Pain

Postmicturition dribble in men with no previous urogenital surgery: Systematic review and meta-analysis of treatment modalities. (PubMed, Neurourol Urodyn) - "Physical/behavioral therapy and PDE5 inhibitors are effective primary PMD treatments. PMD management studies in males with no previous urethral/prostatic surgery are very scarce and lack the use of consistent/comparable outcome measures. Further studies addressing these deficiencies would benefit this very thin evidence base."

Journal • Retrospective data • Review • Surgery • Urinary Incontinence • Urology • Women's Health

The Effect of Udenafil on Heart Rate and Blood Pressure in Adolescents With the Fontan Circulation. (PubMed, Am J Cardiol) - "There were no clinically significant differences between treatment and placebo group in change in HR or blood pressure in the youngest age quartile, lightest weight quartile, or those on afterload-reducing agents. In conclusion, initiation of treatment with udenafil in patients with Fontan circulation was not associated with clinically significant changes in vital signs, implying that for patients similar to those enrolled in the FUEL trial, udenafil can be started without the requirement for additional monitoring after initial administration."

Clinical • Journal • Cardiovascular • Heart Failure

FUEL-2: Fontan Udenafil Exercise Longitudinal Assessment Trial - 2 (clinicaltrials.gov) - P3 | N=436 | Recruiting | Sponsor: Mezzion Pharma Co. Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Heart Failure

Phosphodiesterase 5 inhibitors: preclinical and early phase breakthroughs for impotence treatments. (PubMed, Expert Opin Investig Drugs) - "Our review of udenafil, mirodenafil, youkenafil, lodenafil, and SLx-2101 analyzes the safety, efficacy, and pharmacokinetic properties of these new ED drugs. It is our opinion that more robust clinical trials are required before these medications can be made available in the United States. Additionally, the field of urology may benefit from pursuing other avenues of pharmacotherapy, such as injections, tablets with a different mechanism of action, or stem cell therapy, to restore the integrity of the endothelium within the penis."

Journal • Preclinical • Review • Erectile Dysfunction • Urology

The Fontan Udenafil Exercise Longitudinal Trial: Subgroup Analysis. (PubMed, Pediatr Cardiol) - P3 | "The absence of a differential response across subgroups in response to treatment with udenafil suggests that the treatment benefit may not be restricted to specific sub-populations. Further work is warranted to confirm the potential benefit of udenafil and to evaluate the long-term tolerability and safety of treatment and to determine the impact of udenafil on the development of other morbidities related to the Fontan circulation.Trial Registration NCT0274115."

Journal • Pediatrics

FUEL-2: Fontan Udenafil Exercise Longitudinal Assessment Trial - 2 (clinicaltrials.gov) - P3 | N=436 | Not yet recruiting | Sponsor: Mezzion Pharma Co. Ltd

New P3 trial • Cardiovascular • Heart Failure

A pilot study to explore the effect of udenafil on cerebral hemodynamics in older adults. (PubMed, Ann Clin Transl Neurol) - "Our results showed a paradoxical effect of udenafil on cerebral hemodynamics in older adults. This contradicts our hypothesis, but it suggests that fNIRS is sensitive to changes in cerebral hemodynamics in response to PDE5Is."

Journal

Impact of Udenafil on Echocardiographic Indices of Single Ventricle Size and Function in FUEL Study Participants. (PubMed, Circ Cardiovasc Imaging) - P3 | "FUEL participants who received udenafil demonstrated a statistically significant improvement in some global and diastolic echo indices. Although small, the changes in diastolic function suggest improvement in pulmonary venous return and/or augmented ventricular compliance, which may help explain improved exercise performance in that cohort."

Journal

Efficacy and Safety of Udenafil Once Daily in Patients with Erectile Dysfunction after Bilateral Nerve-Sparing Robot-Assisted Laparoscopic Radical Prostatectomy: A Randomized, Double-Blind, Placebo-Controlled Study. (PubMed, World J Mens Health) - "Udenafil 75 mg once daily after BNS-RALP improved the erectile function without any severe adverse effects."

Clinical • Journal • Erectile Dysfunction • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Using a quantum dot bead-based lateral flow immunoassay to broadly detect the adulteration of PDE-5 inhibitors in functional foods. (PubMed, Anal Methods) - "For the determination of lodenafil, methisosildenafil, mirodenafil, udenafil and tadalafil, the limit of detection (LOD) and IC ranged from 1.01 to 26.91 ng mL and 12.75 to 278 ng mL, respectively. In addition, the validity and the consistency have been confirmed with a comparison between QB-LFIA and HPLC-MS/MS (R = 0.9957). Furthermore, the developed QB-LFIA was employed for the inspection of real products, and several samples were found to be adulterated with lodenafil and methisosildenafil."

Journal

Rubus occidentalis and Ellagic Acid Affect the Contractility of Penile Corpus Cavernosum Smooth Muscle through the Nitric Oxide-Cyclic Guanosine Monophosphate and Cyclic Adenosine 3',5'-Monophosphate Signaling Pathway. (PubMed, J Clin Med) - "The interaction of ROE or EA with phosphodiesterase (PDE) 5 and PDE4 inhibitors, such as udenafil (UDE) and rolipram (ROL), were also evaluated...Furthermore, the treatment of ROE and EA markedly increased the UDE- and ROL-induced relaxation of the PCCSM. In conclusion, ROE and EA induced PCCSM relaxation by activating the nitric oxide (NO)-cGMp and cAMp signaling pathways and may have a synergistic action to improve erectile function."

Journal • Erectile Dysfunction • NOS3

Ultra-high performance liquid chromatography-orbitrap high-resolution mass spectrometry for rapid screening and identification of 32 illegally added drugs in slimming and anti-impotence health foods (PubMed, Se Pu) - "Except dapoxetine, hydroxythiohomo sildenafil, thiohomo sildenafil, thiosildenafil, desmethyl thiosildenafil, the recoveries ranged from 50.5% to 84.5% in the solid matrix, with the relative standard deviations (RSDs) ranging from 1.2% to 13%...The limits of detection (LODs) were 0.02 mg/kg for the 32 drugs in the liquid sample and 0.02 mg/kg for 29 compounds in the solid sample; the LODs for chlorothalidone, udenafil, and desmethyl thiosildenafil in the solid sample were 0.04 mg/kg...This method has the advantages of simple operation and high accuracy. It can be used for the rapid screening and confirmation of 32 illegally added drugs in slimming and anti-impotence health foods."

Journal • Erectile Dysfunction

Lodenafil. (PubMed, Profiles Drug Subst Excip Relat Methodol) - "Lodenafil is a class of drugs called an inhibitor of PDE5 which also include a wide range of other erectile medicines, such as sildenafil, tadalafil and vardenafil. It is part of a new generation of PDE5 inhibitors that includes udenafil and avanafil...This article discusses, by a critical comprehensive review of the literature on lodenafil in terms of its description, names, formulae, elemental composition, appearance, and therapeutic uses. The article also discusses the methods for preparation of lodenafil, its physical-chemical properties, analytical methods for its determination, pharmacological-toxicological properties, and dosing information."

Journal

"@djgfromhp @SIwa23288585 @sasha_opo @mgoschu @AriCedars @FredWuMD @ralogon @jkurtz02 @ZakkisMom In Fontan except Superfontan(predicted peak VO2>80), Udenafil achieved statistical significance in max VO2(p=0.023) & showed improvement in liver at FALDtrial." (@polycle)

The Effect of Udenafil on Stasis Zone in an Experimental Burn Model. (PubMed, Ann Plast Surg) - "Udenafil treatment improved tissue survival on zone of stasis in. Future experimental studies should be conducted to develop zone of stasis treatment protocols combining udenafil with potent anti-inflammatory and antioxidant drugs."

Journal • Immunology • Inflammation