A5074942020- Urinary Tract Infections Management
- Pediatric Urology and Nephrology Studies
- HIV/AIDS drug development and treatment
- Antibiotics Pharmacokinetics and Efficacy
- Helminth infection and control
- Inhalation and Respiratory Drug Delivery
- Urinary Bladder and Prostate Research
- Nephrotoxicity and Medicinal Plants
- Pediatric Hepatobiliary Diseases and Treatments
- Agricultural safety and regulations
- Obstructive Sleep Apnea Research
- Neutropenia and Cancer Infections
- Asthma and respiratory diseases
- Vitamin K Research Studies
- Viral Infections and Vectors
- HIV Research and Treatment
- Parasitic Diseases Research and Treatment
- Antibiotic Resistance in Bacteria
- Respiratory viral infections research
- Neuroscience of respiration and sleep
- Neuropeptides and Animal Physiology
- Drug-Induced Hepatotoxicity and Protection
- Pharmacological Effects and Toxicity Studies
- Liver Diseases and Immunity
- Drug Transport and Resistance Mechanisms
Hammersmith Medicines Research
2018-2021
GlaxoSmithKline (United Kingdom)
2021
GlaxoSmithKline (United States)
2021
Covance (United Kingdom)
2021
Abstract Background Uncomplicated urinary tract infections (uUTIs), usually caused by Escherichia coli (E. coli), are common infections, affecting ∼50% of women globally in their lifetime. The presence extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales limits effective oral treatment options for uUTI. Using uropathogen susceptibility data from two randomized controlled trials (RCTs) uUTI, we compared baseline characteristics patients with ESBL-positive (ESBL+) versus non-ESBL...
Abstract Background Two Phase 3 trials (EAGLE-2 [NCT04020341]/EAGLE-3 [NCT04187144]) showed that gepotidacin, a first-in-class triazaacenaphthylene antibacterial, was non-inferior to nitrofurantoin (NTF) in treating uncomplicated urinary tract infection (uUTI) caused by NTF-susceptible (NTF-S) qualifying uropathogens (≥ 105 CFU/mL).1 This study evaluates gepotidacin efficacy the pooled EAGLE-2/3 microbiological intent-to-treat (micro-ITT) NTF not susceptible (NTF-NS) population. Methods In...
Abstract Background Regulatory guidance recommends the primary endpoint for uncomplicated urinary tract infection (uUTI) trials be a composite of clinical and microbiological response. However, discordant outcomes have raised questions regarding utility component. The aim this post hoc analysis was to explore significance based on pooled data from two recent Phase 3 in uUTI (EAGLE-2 [NCT04020341]/-3 [NCT04187144]). Methods EAGLE-2/-3 compared gepotidacin (1500mg) nitrofurantoin (NTF; 100mg),...
Plain Language SummaryWhat is this summary about?Gepotidacin a new oral antibiotic that under investigation as treatment for certain infections. This of two clinical studies gepotidacin: EAGLE-2 and EAGLE-3 which researched how well gepotidacin works the uncomplicated urinary tract infection (uUTI; acute cystitis, bladder infection), whether there were any side effects drug (any effect was beyond its desired effect). Results from these published in The Lancet February 2024. Researchers...
The objectives of this study were to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics single multiple oral doses ONO-7684, a novel activated factor XI (FXIa) inhibitor, in healthy subjects.
Aims Emodepside is an anthelmintic, originally developed for veterinary use. We investigated in healthy subjects the safety, and pharmacokinetics of a liquid service formulation (LSF) immediate release (IR) tablet emodepside 2 randomised, parallel‐group, placebo‐controlled, Phase I studies. Methods Seventy‐nine 10 cohorts single ascending dose study 24 3 ascending‐dose multiple were enrolled. as LSF was administered orally 1–40‐mg doses days 5 or mg once daily 10‐mg twice doses,...
Chronic obstructive pulmonary disease (COPD) is an inflammatory lung condition, causing progressive decline in function leading to premature death. Acute exacerbations COPD patients are predominantly associated with respiratory viruses. Ribavirin a generic broad-spectrum antiviral agent that could be used for treatment of viral infections COPD. Using the Particle Replication In Nonwetting Templates (PRINT) technology, which produces dry-powder particles uniform shape and size, two new...
Linerixibat, an oral small-molecule ileal bile acid transporter inhibitor under development for cholestatic pruritus in primary biliary cholangitis, was designed minimal absorption from the intestine (site of pharmacological action). This study characterized pharmacokinetics, absorption, metabolism, and excretion [<sup>14</sup>C]-linerixibat humans after intravenous microtracer concomitant with unlabeled tablets solution. Linerixibat exhibited absorption-limited flip-flop kinetics: longer...
Abstract The use of positron emission tomography (PET) in early-phase development novel drugs targeting the central nervous system, is well established for evaluation brain penetration and target engagement. However, when targets are involved a suitable PET ligand not always available. We demonstrate an alternative approach that evaluates attenuation amphetamine-induced synaptic dopamine release by agonist orphan G-protein-coupled receptor GPR139 (TAK-041). agonism candidate mechanism...
Amenamevir (formerly ASP2151) is a helicase-primase inhibitor being developed for the treatment of herpesvirus infection. both substrate and inducer cytochrome P450 (CYP) 3A4. Three studies were done in healthy volunteers to investigate potential CYP3A pharmacokinetic interactions with following drugs: (1) Midazolam (probe CYP3A): After 10 days' pretreatment amenamevir 400 mg daily, geometric mean maximum concentration drug blood plasma (Cmax ) area under concentration-time curve from time...
Abstract Amenamevir (formerly ASP2151) induces cytochrome P450 (CYP)2B6 and CYP3A4 inhibits CYP2C8. We conducted 2 studies, 1 using montelukast as a probe to assess CYP2C8 the other bupropion CYP2B6. The study examined effect of amenamevir on pharmacokinetics in 24 healthy men: each subject received 10 mg alone, followed by with 400 mg, or vice versa after washout period. In study, subjects single dose 150 days 1, 15, 22, 29, repeated once‐daily doses 6‐15. increased peak concentration area...
Abstract Background Uncomplicated urinary tract infections (uUTIs) are among the most prevalent worldwide. Currently, treatments limited by antimicrobial resistance and antibiotic allergy/intolerance. There is an unmet need for new oral antibiotics active against uropathogens resistant to current treatments. Gepotidacin a novel, bactericidal, first-in-class triazaacenaphthylene that inhibits bacterial DNA replication distinct mechanism of action binding site provides well-balanced inhibition...
Abstract Background Uncomplicated urinary tract infections (uUTI) are among the most common community-acquired in women worldwide. Recommended treatment is largely empiric. Rates of antimicrobial resistance Escherichia coli (E. coli) isolates, specifically extended-spectrum beta-lactamase positive (ESBL+) and multidrug-resistant (MDR) strains, increasing Gepotidacin a first-in-class, triazaacenaphthylene, bactericidal antibiotic that inhibits bacterial DNA replication by inhibiting two...
Motivation: Obstructive sleep apnea (OSA) is a common disorder predisposing patients to heart disease, stroke, and cognitive dysfunction. Goal(s): To gain insights into the association between brain metabolism changes in upper airway architecture during spontaneous apneas scanner. Approach: A time-resolved pulse sequence was designed that yields neurometabolic parameters anatomy at 6-second temporal resolution, along with EEG monitoring 90-minute scan. Results: Data demonstrate associations...
Aims: Emodepside is an anthelmintic, originally developed for veterinary use. We investigated the safety, pharmacokinetics, relative bioavailability and dose linearity of four oral formulations emodepside in healthy male subjects. Methods: Three randomised, parallel‐group, controlled, Phase I studies were conducted using various formulations, involving 79 subjects ten cohorts single-ascending-dose study, 24 three ascending-dose multiple-ascending-dose study 77 seven different study....
Abstract Background For noninferiority RCTs in uUTIs, the latest US Food and Drug Administration (FDA; 2019)/European Medicines Agency (EMA; 2018) guidance recommends a primary endpoint of therapeutic response (combined clinical microbiologic response) with success defined by full symptom resolution plus microbiological eradication from ≥ 105 to &lt; 103 CFU/mL. Historically, less stringent criteria (clinical or [not combined], allowing improvement/resolution) various endpoints were...
Abstract Background Two large Phase 3 trials showed that gepotidacin, a first-in-class oral triazaacenaphthylene bactericidal antibiotic, was efficacious in treating uncomplicated urinary tract infection (uUTI) females and had an acceptable safety profile consistent with prior gepotidacin trials. We now present pooled analysis of the EAGLE-2 EAGLE-3 to evaluate efficacy patient subgroups. Methods Data were from EAGLE-3, near identical global, 3, randomized, double-blind, double-dummy,...