A5038870948- Helicobacter pylori-related gastroenterology studies
- Neuroendocrine Tumor Research Advances
- Asthma and respiratory diseases
- Gastroesophageal reflux and treatments
- Respiratory and Cough-Related Research
- Receptor Mechanisms and Signaling
- Pharmaceutical studies and practices
- Allergic Rhinitis and Sensitization
- Ion Transport and Channel Regulation
- Biosimilars and Bioanalytical Methods
- Health Systems, Economic Evaluations, Quality of Life
- Pharmacology and Obesity Treatment
- Analytical Methods in Pharmaceuticals
- Monoclonal and Polyclonal Antibodies Research
- Lung Cancer Research Studies
- Hypothalamic control of reproductive hormones
- Pharmacological Effects and Toxicity Studies
- Biomedical Ethics and Regulation
- Pharmacogenetics and Drug Metabolism
- Pediatric health and respiratory diseases
- Inhalation and Respiratory Drug Delivery
- Neurotransmitter Receptor Influence on Behavior
- Ethics in Clinical Research
- Nausea and vomiting management
- Pharmacological Effects and Assays
Hammersmith Medicines Research
2014-2024
Trio Medicines (United Kingdom)
2016-2024
Schlosspark-Klinik
2020
Charité - Universitätsmedizin Berlin
2020
GlaxoSmithKline (India)
2019
GlaxoSmithKline (United Kingdom)
2019
Babraham Institute
2019
Bon Secours Hospital Cork
2017
University College Cork
2017
Central Middlesex Hospital
2004-2016
Advancement of RNAi-based therapeutics depends on effective delivery to the site protein synthesis. Although intravenously administered, multi-component vehicles have enabled small interfering RNA (siRNA) and progression into clinical development, advances single-component, systemic siRNA been challenging. In pre-clinical models, attachment a triantennary N-acetylgalactosamine (GalNAc) ligand an mediates hepatocyte uptake via asialoglycoprotein receptor enabling RNAi-mediated gene silencing....
Patients with chronic atrophic gastritis have long-term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop ECL cells carcinoids (type 1 GC). Most type GC remain indolent, but some metastasise. undergo surveillance, are treated somatostatin analogues, endoscopic resection or surgery. Netazepide (YF476) is a highly selective, potent orally active gastrin receptor antagonist, which has anti-tumour activity in various rodent models of neoplasia driven by been studied healthy...
Background and Purpose Anaemia of chronic disease is characterized by impaired erythropoiesis due to functional iron deficiency, often caused excessive hepcidin. Lexaptepid pegol, a pegylated structured l ‐oligoribonucleotide, binds inactivates Experimental Approach We conducted placebo‐controlled study on the safety, pharmacokinetics pharmacodynamics lexaptepid after single repeated i.v. s.c. administration 64 healthy subjects at doses from 0.3 4.8 mg·kg −1 . Key Results After treatment...
Netazepide, a gastrin/cholecystokinin 2 receptor antagonist, once daily for 12 weeks reduced the number of tumours and size largest one in 16 patients with autoimmune chronic atrophic gastritis (CAG), achlorhydria, hypergastrinaemia multiple gastric neuroendocrine (type 1 NETs), normalized circulating chromogranin A (CgA) produced by enterochromaffin-like cells, source tumours. The aim was to assess whether longer-term netazepide treatment can eradicate type NETs.After mean 14 months off...
The incidence of esophageal adenocarcinoma (EAC) is increasing, but factors contributing to malignant progression its precursor lesion, Barrett's esophagus (BE), have not been defined. Hypergastrinemia caused by long-term use proton pump inhibitors (PPIs), has suggested as one possible risk factor. gastrin receptor, CCK2R, expressed in the cardia and upregulated BE, suggesting involvement gastrin-CCK2R pathway progression. In L2-IL-1β mouse model, Barrett's-like arises from gastric cardia....
Background Due to their potential impact on mood and wellbeing there has been increasing interest in the of serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) treatment major depressive disorder (MDD). Aim The aim Part A this study was evaluate safety, tolerability, pharmacokinetics (PK) pharmacodynamic (PD) profile escalating doses SPL026 (DMT fumarate) psychedelic-naïve healthy participants determine a dose for administration patients with MDD subsequent Phase 2a part trial...
To assess the steady-state pharmacokinetic and QT(c) effects of domperidone ketoconazole, given alone together.A randomized, placebo-controlled, double-blind, crossover study was carried out. Healthy subjects (14 men, 10 women; age 18-39 years; mean weight 73.5kg, range 53.8-98.8kg; 23 Europid, 1 Afro-Caribbean) received orally, for 7 days each, placebo, 10mg, four doses daily, at 4h intervals, ketoconazole 200mg 12-hourly together. The washout period 15 days. Pharmacokinetics serial 12-lead...
IntroductionAutoimmune chronic atrophic gastritis (CAG) causes hypochlorhydria and hypergastrinaemia, which can lead to enterochromaffin-like (ECL) cell hyperplasia gastric neuroendocrine tumours (type 1 NETs). Most behave indolently, but some larger metastasise. Antrectomy, removes the source of usually tumour regression. Non-clinical healthy-subject studies have shown that netazepide (YF476) is a potent, highly selective orally-active gastrin/CCK-2 receptor antagonist. Also, it effective...
Interleukin-13 (IL-13) is a key mediator of T-helper-cell-type-2 (Th-2)-driven asthma, the inhibition which may improve treatment outcomes. We examined safety, pharmacokinetics, pharmacodynamics, and immunogenicity VR942, dry-powder formulation containing CDP7766, high-affinity anti-human-IL-13 antigen-binding antibody fragment being developed for asthma.We conducted phase 1, randomized, double-blind, placebo-controlled, ascending-dose study at Hammersmith Medicines Research, London, UK, now...
Aims To compare the pharmacokinetics, safety, tolerability and immunogenicity of FKB327, a biosimilar adalimumab, with European Union (EU)‐approved Humira US‐licensed after single subcutaneous doses in healthy subjects. Methods In randomized, double‐blind, parallel‐group study, 180 subjects received by injection 40 mg EU‐Humira, or US‐Humira, 1:1:1 ratio, stratified bodyweight. Pharmacokinetics, local tolerability, immunogenicity, adverse events, vital signs, electrocardiography laboratory...
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.
Abstract SLN124, an N‐acetylgalactosamine conjugated 19‐mer short interfering RNA, is being developed to treat iron‐loading anemias (including beta‐thalassemia and myelodysplastic syndromes) myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This first clinical report siRNA a component iron homeostasis. first‐in‐human, phase 1 study assessed safety, tolerability, pharmacokinetics,...
Cathepsin C (CTSC) is necessary for the activation of several serine proteases including neutrophil elastase (NE), cathepsin G and proteinase 3. GSK2793660 an oral, irreversible inhibitor CTSC that hypothesized to provide alternative route achieve NE inhibition was tested in a Phase I study.Single escalating oral doses from 0.5 20 mg or placebo were administered randomized crossover design healthy male subjects; separate cohort received once daily 12 21 days. Data collected on safety,...
CHF6001 is an inhaled phosphodiesterase 4 (PDE4) inhibitor in development for the treatment of obstructive lung diseases. The efficacy and safety were investigated a double blind, placebo controlled, 3-way cross-over study using allergen challenge model. Thirty-six atopic asthmatics who not taking corticosteroids demonstrated late asthmatic response (LAR) to at screening randomised receive 400 μg or 1200 administered once day dry powder inhaler. three periods 9 days; challenges performed on...
A cross‐over study of glycosylated and non‐glycosylated G‐CSF was performed in 20 healthy male volunteers to compare the effects different forms G‐CSF, extent inter‐individual progenitor cell mobilization determine whether any differences observed were related serum concentrations attained. The peak WBC achieved during 6 d administration at a dose 5 μg/kg/d significantly higher with than product ( P = 0.02) as level granulocyte‐monocyte colony forming cells (GM‐CFC) 0.03). average GM‐CFC...
Summary Aim : To compare the antisecretory effects of rabeprazole and esomeprazole in an open, randomized, two‐way crossover, clinical pharmacology study. Methods Twenty‐four healthy subjects (14 men, 10 women; mean age 26.8 years) received 20 mg or daily on days 1–5, witha 14‐day ‘wash‐out’. Intragastric pHwasrecordedcontinuously, serum gastrin measured, 0, 1 5. Results On day intragastric pH AUC was significantly higher before than treatment four five time intervals analysed. 5, after...
Objective. Gastric carcinoids (neuroendocrine tumors) arise from enterochromaffin-like cells in the gastric mucosa. Most are caused by hypergastrinemia. The objectives were to determine if their prevalence Europe, USA and Japan meets criteria for an orphan disease justify treatment with a gastrin/CCK2 receptor antagonist. Methods. We obtained data European cancer registries, searched PubMed. Results. Prevalence per 10,000 population registries was: median 0.32 (range 0.09–0.92) Europe; 0.17...
Two double-blind, randomized studies were conducted to assess the tolerability, pharmacokinetics and pharmacodynamics of oral TA-8995, a new cholesteryl ester transfer protein (CETP) inhibitor, in healthy subjects.Study 1: Subjects received single doses TA-8995 or placebo (fasted). Doses 5, 10, 25, 50 (fed/fasted), 100 150 mg (Caucasian males, 18-55 years), 25 > 65 years Caucasian females, 50, (Japanese years). Study 2: males (18-55 years) 1, 2.5, 10 once daily for 21-28 days. Blood urine...
Elevated circulating concentrations of the hormone gastrin contribute to development gastric adenocarcinoma and types-1 2 neuroendocrine tumors (NETs). MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate proteins which in turn influence various biological processes. We hypothesised induces expression specific miRNAs within CCK2 receptor (CCK2R) expressing cells these mediate functionally important actions gastrin.Gastrin increased miR-222 AGSGR cells, with...
Among the vinca-alkaloid class, vincristine is a potent chemotherapeutic agent with significant neurotoxic effects and employed to address wide spectrum of cancer types. Recently, therapeutic potential cholecystokinin type 2 receptor (CCK2R) as target for vincristine-induced peripheral neuropathy (VIPN) was demonstrated. In this study, impact preventive CCK2R blockade using netazepide (Trio Medicines Ltd., London, UK) investigated in mouse model neuropathy. Netazepide highly selective...