Article date: June 2016
By: 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 in Volume 173, Issue 11, pages 1768-1777
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). Gastric emptying (13C‐octanoic acid breath test), pharmacokinetics and safety were primary outcomes.
Key Results
Nine of the 10 patients enrolled completed the study. Gastric half‐emptying time decreased by −95 min (95% CI: −156.8, −34.2) after a single dose of camicinal 125 mg compared with placebo (52 vs. 147 min, P < 0.05), representing a 65% improvement. A decrease of the gastric half‐emptying time compared with placebo (approximately 39 min) was observed with camicinal 25 and 50 mg, representing a 27% reduction for both doses (not statistically significant). A positive exposure–response relationship was demonstrated across all doses. The effects of camicinal on gastric half‐emptying time were not influenced by fasting glucose levels. Single doses up to 125 mg were well tolerated. Camicinal was well absorbed, exhibiting linear and approximately dose‐proportional pharmacokinetic characteristics and a clear exposure–response relationship with gastric emptying.
Conclusions and Implications
Camicinal significantly accelerated gastric emptying of solids in T1DM patients following administration of a single oral dose. Camicinal was well tolerated and exhibited similar pharmacokinetic characteristics in diabetic patients to those previously reported in healthy volunteers.
DOI: 10.1111/bph.13475
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