The effects of camicinal, a novel motilin agonist, on gastro-esophageal function in healthy humans-a randomized placebo controlled trial.
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 1.5-h post dose) and 24-h ambulatory multichannel intraluminal impedance/pH. After a standardized meal, subjects ingested a wireless motility capsule from which compartmental transit times and motility indices were derived. Subjects were restudied with the alternate intervention after 7 days.


RESULTS
The study subjects (12 male, mean age 47.4 years, range 22-55) tolerated the drug well, except one who exhibited mild abdominal pain on both placebo and camicinal. In comparison to placebo, gastric emptying time (GET) was accelerated following camicinal (-115.4 min, 95% confidence interval -194.4, -36.4, p = 0.009). No effect was demonstrable on esophageal function, small bowel, colonic, or whole bowel transit times and motility indices. With camicinal, as part of a post hoc analysis, there was a trend association between the percentage reduction in GET and total number of acidic reflux events (r = 0.56, p = 0.09).


CONCLUSIONS
Camicinal decreases GET and was generally well-tolerated. In health, the direct effects of camicinal are on accelerating GET with a potential secondary benefit of reducing reflux events, which warrant further exploration in patient cohorts.
Functional Gut Clinic, London, UK.
R
R
Hobson
Centre for Digestive Diseases, Blizard Institute of Cell & Molecular Science, Wingate Institute of Neurogastroenterology, Barts and the London School of Medicine & Dentistry, Queen Mary University of London, London, UK.|Department of Gastroenterology, University Hospitals of North Midlands, Stoke on Trent, Staffordshire, UK.
A D
AD
Farmer
GlaxoSmithKline Research & Development Ltd, Cambridge, UK.
O E
OE
Dewit
GlaxoSmithKline Research & Development Ltd, Cambridge, UK.
M
M
O'Donnell
GlaxoSmithKline Research & Development Ltd, Cambridge, UK.
K
K
Hacquoil
GlaxoSmithKline Research & Development Ltd, Cambridge, UK.
D
D
Robertson
GlaxoSmithKline, Research Triangle Park, NC, USA.
M E
ME
Barton
GlaxoSmithKline, Research Triangle Park, NC, USA.
G E
GE
Dukes
D000328:Adult; D053704:Capsule Endoscopy; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004943:Esophagogastric Junction / Q000187:drug effects*; D005746:Gastric Emptying / Q000187:drug effects*; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008365:Manometry; D008875:Middle Aged; D009037:Motilin / Q000819:agonists*; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D055815:Young Adult
D005765:Gastrointestinal Agents; C541863:N-(3-fluorophenyl)-1-((4-(((3S)-3-methyl-1-piperazinyl)methyl)phenyl)acetyl)-4-piperidinamine; D010879:Piperazines; D010880:Piperidines; D009037:Motilin
gastro-esophageal reflux; lower esophageal sphincter; motilin agonist