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Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics.

ABSTRACT: 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).In a randomized crossover study, 10 female patients received RM-131 (100 ?g 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).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 (?) 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.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.

SUBMITTER: Shin A

PROVIDER: S-EPMC3526234 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics.

Shin Andrea A Camilleri Michael M Busciglio Irene I Burton Duane D Stoner Elizabeth E Noonan Patrick P Gottesdiener Keith K Smith Steven A SA Vella Adrian A Zinsmeister Alan R AR

Diabetes care 20120906 1

<h4>Objective</h4>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).<h4>Research design and methods</h4>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 po ...[more]

PMID: 22961573

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Project description:Background & aimsRM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE.MethodsIn a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m(2)) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale).ResultsAt screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects.ConclusionsRM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.

Dataset Information

Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics.

Publications

Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics.

Similar Datasets

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