A novel partial 5HT3 agonist DDP733 after a standard refluxogenic meal reduces reflux events: a randomized, double-blind, placebo-controlled pharmacodynamic study.
BACKGROUND
DDP733, a selective partial 5HT(3) receptor agonist, increases lower oesophageal sphincter pressure in experimental animal models. However, its effect on gastro-oesophageal reflux or lower oesophageal sphincter pressure in humans remains unknown.


OBJECTIVE
To evaluate the effect of DDP733 on reflux episodes in healthy volunteers receiving a refluxogenic meal.


METHODS
A randomized, double-blind, placebo-controlled cross-over study evaluated the pharmacodynamic effects of DDP733 (0.5, 0.8 and 1.4 mg). Healthy subjects underwent oesophageal manometry and intra-oesophageal multichannel intraluminal impedance and pH after a refluxogenic meal.


RESULTS
DDP733 0.5 mg significantly (P = 0.013) reduced the rate of reflux episodes after a refluxogenic meal from 10 (+/-2.2) on placebo to 6 (+/-1.2) on drug over a 2-h period. DDP733 0.8 and 1.4 mg had no significant effect on reducing the number of reflux episodes. Significant differences in resting lower oesophageal sphincter pressure and the proportion of time pH was <4 (placebo minus drug) after a refluxogenic meal were not observed. No serious adverse events were reported.


CONCLUSIONS
In healthy subjects, the partial 5HT(3) agonist DDP733 at a dose of 0.5 mg significantly reduces the rate of reflux events, but did not result in a significant change in lower oesophageal sphincter pressure at 1 h postdosing.
Choung
R S
RS
Mayo Clinic College of Medicine, Division of Gastroenterology and Hepatology, Jacksonville, FL, USA.
Ferguson
D D
DD
Murray
J A
JA
Kammer
P P
PP
Dierkhising
R A
RA
Zinsmeister
A R
AR
Nurbhai
S
S
Landau
S B
SB
Talley
N J
NJ
D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D017097:Electric Impedance; D005260:Female; D005502:Food; D005764:Gastroesophageal Reflux / Q000503:physiopathology*; D005765:Gastrointestinal Agents / Q000009:adverse effects / Q000494:pharmacology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008365:Manometry; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology*
C527576:DDP733; D005765:Gastrointestinal Agents; D011725:Pyridines; D017366:Serotonin Receptor Agonists