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.

Trial registration: ClinicalTrials.gov NCT00861809.

© 2016 The British Pharmacological Society.

Figures

Figure 1

Exposure–response relationship of gastric half‐emptying time by AUC (0–∞); median prediction (solid line) and 90% prediction interval (dashed lines) from population PK/PD model shown.

Figure 2

Scatter plot of gastric half‐emptying time by fasting plasma glucose concentration.

Figure 3

Pancreatic polypeptide 30 min post‐meal.

Figure 4

Plot of mean (±SD) plasma glucose profiles following placebo or camicinal 125 mg. Black line is the mean placebo glucose profile with SD as gray shaded area; red line is the camicinal 125 mg mean glucose profile with SD as pink shaded area.