The pharmacodynamics, safety and pharmacokinetics of single doses of the motilin agonist, camicinal, in type 1 diabetes mellitus with slow gastric emptying.

Abstract

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 ((13) C-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.

• Authors: 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
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 173 Issue 11 Pg. 1768-77 (06 2016) ISSN: 1476-5381 [Electronic] England
• PMID: 26924243 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 The British Pharmacological Society.

Chemical References

• Gastrointestinal Agents
• N-(3-fluorophenyl)-1-((4-(((3S)-3-methyl-1-piperazinyl)methyl)phenyl)acetyl)-4-piperidinamine
• Piperazines
• Piperidines
• Motilin

Topics

• Adolescent
• Adult
• Aged
• Diabetes Mellitus, Type 1 (drug therapy, metabolism)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Gastric Emptying (drug effects)
• Gastrointestinal Agents (administration & dosage, adverse effects, pharmacokinetics)
• Humans
• Middle Aged
• Motilin (agonists, metabolism)
• Piperazines (administration & dosage, adverse effects, pharmacokinetics)
• Piperidines (administration & dosage, adverse effects, pharmacokinetics)
• Young Adult