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Sarah L Marrinan, Tal Otiker, Lakshmi S Vasist, Rachel A Gibson, Bhopinder K Sarai, Matthew E Barton, Duncan B Richards, Per M Hellström, Dag Nyholm, George E Dukes, David J Burn
BACKGROUND: Delayed gastric emptying may impair l-dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l-dopa and symptoms of PD. METHODS: Phase II, double-blind, placebo-controlled trial. Participants were randomized to receive camicinal 50 mg once-daily (n = 38) or placebo (n = 20) for 7 to 9 days. RESULTS: l-dopa exposure was similar with coadministration of camicinal compared to placebo...
February 2018: Movement Disorders: Official Journal of the Movement Disorder Society
E Deloose, I Depoortere, J de Hoon, A Van Hecken, O E Dewit, L S Vasist Johnson, M E Barton, G E Dukes, J Tack
BACKGROUND: The gut hormone motilin stimulates gastrointestinal motility by inducing gastric phase III of the migrating motor complex (MMC) and enhancing the rate of gastric emptying. Camicinal (GSK962040), a small molecule motilin receptor agonist, has been shown to increase gastrointestinal motility. METHODS: In this proof of concept study the effects of camicinal on MMC activity, esophageal and gastric pH was evaluated in eight healthy volunteers as a secondary endpoint...
January 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Marianne J Chapman, Adam M Deane, Stephanie L O'Connor, Nam Q Nguyen, Robert J L Fraser, Duncan B Richards, Kimberley E Hacquoil, Lakshmi S Vasist Johnson, Matthew E Barton, George E Dukes
BACKGROUND: The promotility agents currently available to treat gastroparesis and feed intolerance in the critically ill are limited by adverse effects. The aim of this study was to assess the pharmacodynamic effects and pharmacokinetics of single doses of the novel gastric promotility agent motilin agonist camicinal (GSK962040) in critically ill feed-intolerant patients. METHODS: A prospective, randomized, double-blind, parallel-group, placebo-controlled, study was performed in mechanically ventilated feed-intolerant patients [median age 55 (19-84), 73 % male, APACHE II score 18 (5-37) with a gastric residual volume ≥200 mL]...
August 1, 2016: Critical Care: the Official Journal of the Critical Care Forum
Per M Hellström, Jan Tack, Lakshmi Vasist Johnson, Kimberley Hacquoil, Matthew E Barton, Duncan B Richards, David H Alpers, Gareth J Sanger, George E Dukes
BACKGROUND AND PURPOSE: Here we have investigated the pharmacokinetics, pharmacodynamics and safety of single doses of camicinal in type 1 diabetes mellitus (T1DM) patients with a history of slow gastric emptying with symptoms consistent with gastroparesis. EXPERIMENTAL APPROACH: In a randomized, double-blind, placebo-controlled, incomplete block, three-period, two-centre crossover study, patients received oral administration of placebo and two of the three possible doses of camicinal (25, 50 or 125 mg)...
June 2016: British Journal of Pharmacology
Michael Camilleri
This review of the pathophysiologic basis for gastroparesis and recent advances in the treatment of patients with gastroparesis shows that there are several novel approaches to advance treatment of gastroparesis including diet, novel prokinetics, interventions on the pylorus, and novel forms of gastric electrical stimulation. The field of gastroparesis is likely to advance with further studies, with help from a guidance document from the Food and Drug Administration on gastroparesis, and with recent approval of the stable isotope gastric emptying test to ensure eligibility of participants in multicenter trials...
August 2016: Clinical Gastroenterology and Hepatology
R Hobson, A D Farmer, O E Dewit, M O'Donnell, K Hacquoil, D Robertson, M E Barton, G E Dukes
BACKGROUND: A proportion of patients with foregut dysmotility fail to respond to standard interventions. Motilin agonists may be beneficial in this group. We aimed to determine the effect of camicinal, a novel motilin agonist, on gastrointestinal physiology in healthy volunteers. METHODS: Healthy male subjects were randomly assigned to receive a single dose of 125 mg camicinal or placebo in a double-blind cross-over design. Esophageal function and reflux indices were assessed using high-resolution manometry (pre and 1...
November 2015: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Alkesh V Zala, Marjorie M Walker, Nicholas J Talley
INTRODUCTION: Functional dyspepsia (FD) is a relatively common gastrointestinal clinical condition that remains poorly understood. Controversies remain regarding the definition, pathophysiology and optimum treatment. The current treatment of FD is limited and no established regimen is available. AREAS COVERED: Recent advances have improved our understanding of the pathophysiology of the disease and have led to the development of newer tailored therapies. Novel agents such as the motilin receptor agonist camicinal and the muscarinic M1 and M2 receptor antagonist acotiamide appear promising; however, the need for a safe and efficacious treatment remains largely unmet...
June 2015: Expert Opinion on Emerging Drugs
Theo L Peeters
PURPOSE OF REVIEW: To summarize the recent findings. RECENT FINDINGS: Studies of changes in the plasma levels confirm the earlier concepts, but offer little proof of causal effect. It is increasingly realized that peptides produced in the gut have a paracrine role or an indirect effect via the gut-brain axis. Interest in prokinetic peptide agonists remains high despite the failure of two candidate drugs, but relamorelin and camicinal offer new hope. SUMMARY: We review the original studies published since January 2013 on peptides produced in the gut and with an effect on gastrointestinal motility...
February 2015: Current Opinion in Endocrinology, Diabetes, and Obesity
Kenneth Barshop, Braden Kuo
Introduction: Gastroparesis is a syndrome of delayed gastric emptying in the absence of mechanical obstruction that presents with upper gastrointestinal symptoms. Despite its growing prevalence, there remains an unmet clinical need for more efficacious prokinetic treatment options. The current market includes prokinetic agents that reduce gastroparesis symptoms. However, adverse drug effects and tachyphylaxis with repeated dosing are among the factors that limit their use. Camicinal (GSK962040) is the most advanced, small-molecule, selective motilin receptor agonist with therapeutic potential to date...
January 2015: Expert Opinion on Investigational Drugs
J Broad, A Góralczyk, K Mannur, G E Dukes, G J Sanger
BACKGROUND: Progress in identifying safer, effective drugs to increase gastric emptying is impeded by failed clinical trials. One potential reason for failure is lack of translation from animal models to the human condition. To make progress, the actions of existing drugs and new therapeutic candidates need to be understood in human isolated stomach. METHODS: Neuromuscular activities were evoked in human gastric antrum circular muscle by electrical field stimulation (EFS), defined phenotypically using pharmacological tools...
June 2014: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
G J Sanger
Ghrelin and motilin receptor agonists increase gastric motility and are attractive drug targets. However, 14 years after the receptors were described (18-24 years since ligands became available) the inactivity of the ghrelin agonist TZP-102 in patients with gastroparesis joins the list of unsuccessful motilin agonists. Fundamental questions must be asked. Pustovit et al., have now shown that the ghrelin agonist ulimorelin evokes prolonged increases in rat colorectal propulsion yet responses to other ghrelin agonists fade...
February 2014: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
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