title: Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics.
abstract: OBJECTIVE
  To investigate the pharmacokinetics (PK), pharmacodynamics, and safety of single-dose RM-131 in type 2 diabetic patients with gastrointestinal cardinal symptoms (GCSI) and previously documented delayed gastric emptying (DGE).
  
  
  METHODS
  In a randomized crossover study, 10 female patients received RM-131 (100 μg s.c.) or placebo and underwent scintigraphic gastric emptying (GE) and colonic filling at 6 h (CF6) of a solid-liquid meal administered 30 min postdosing. Adverse events, plasma glucose, and hormonal levels were assessed. GCSI daily diary (GCSI-DD) was completed during treatments. PK was assessed in this cohort and healthy volunteers (HVs).
  
  
  RESULTS
  At screening, HbA(1c) was 7.2 ± 0.4% (SEM) and total GCSI-DD score was 1.32 ± 0.21. RM-131 accelerated GE t(1/2) of solids (P = 0.011); mean difference (Δ) in solid GE t(1/2) was 68.3 min (95% CI 20-117) or 66.1%. There were numerical differences in GE lag time, CF6 solids, and GE t(1/2) liquids (all P < 0.14). With a significant (P < 0.014) order effect, further analysis of the first treatment period (n = 5 per group) confirmed significant RM-131 effects on GE t(1/2) (solids, P = 0.016; liquids, P = 0.024; CF6, P = 0.013). PK was similar in DGE patients and HVs. There were increases in 120-min blood glucose (P = 0.07) as well as 30-90-min area under the curve (AUC) levels of growth hormone, cortisol, and prolactin (all P < 0.02) with single-dose RM-131. Only light-headedness was reported more on RM-131.
  
  
  CONCLUSIONS
  RM-131 greatly accelerates the GE of solids in patients with type 2 diabetes and documented DGE. PK is similar in diabetic patients and HVs.
authors.affiliation: 1Division of Gastroenterology and Hepatology, Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER), College of Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Shin
authors.forename: Michael
authors.initials: M
authors.lastname: Camilleri
authors.forename: Irene
authors.initials: I
authors.lastname: Busciglio
authors.forename: Duane
authors.initials: D
authors.lastname: Burton
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Stoner
authors.forename: Patrick
authors.initials: P
authors.lastname: Noonan
authors.forename: Keith
authors.initials: K
authors.lastname: Gottesdiener
authors.forename: Steven A
authors.initials: SA
authors.lastname: Smith
authors.forename: Adrian
authors.initials: A
authors.lastname: Vella
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
mesh_terms: D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D018589:Gastroparesis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D054440:Receptors, Ghrelin / Q000819:agonists*
chemical_list: D007004:Hypoglycemic Agents; D054440:Receptors, Ghrelin