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

Andrea Shin, Michael Camilleri, Irene Busciglio, Duane Burton, Elizabeth Stoner, Patrick Noonan, Keith Gottesdiener, Steven A. Smith, Adrian Vella, Alan R. Zinsmeister

Research output: Contribution to journalArticle

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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). RESEARCH DESIGN AND 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, HbA1c was 7.2 ± 0.4% (SEM) and total GCSI-DD score was 1.32 ± 0.21. RM-131 accelerated GE t1/2 of solids (P = 0.011); mean difference (Δ) in solid GE t1/2 was 68.3 min (95% CI 20-117) or 66.1%. There were numerical differences in GE lag time, CF6 solids, and GE t1/2 liquids (all P < 0.14). With a signifi cant (P < 0.014) order effect, further analysis of the first treatment period (n = 5 per group) con fi rmed significant RM-131 effects on GE t1/2 (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.

Original languageEnglish (US)
Pages (from-to)41-48
Number of pages8
JournalDiabetes Care
Volume36
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Fingerprint

Ghrelin
Gastric Emptying
Pharmacokinetics
Healthy Volunteers
relamorelin
Dizziness
Prolactin
Cross-Over Studies
Type 2 Diabetes Mellitus
Growth Hormone
Area Under Curve
Meals
Hydrocortisone
Blood Glucose
Research Design
Placebos
Safety
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying : Pharmacokinetics and pharmacodynamics. / Shin, Andrea; Camilleri, Michael; Busciglio, Irene; Burton, Duane; Stoner, Elizabeth; Noonan, Patrick; Gottesdiener, Keith; Smith, Steven A.; Vella, Adrian; Zinsmeister, Alan R.

In: Diabetes Care, Vol. 36, No. 1, 01.2013, p. 41-48.

Research output: Contribution to journalArticle

Shin, A, Camilleri, M, Busciglio, I, Burton, D, Stoner, E, Noonan, P, Gottesdiener, K, Smith, SA, Vella, A & Zinsmeister, AR 2013, 'Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: Pharmacokinetics and pharmacodynamics', Diabetes Care, vol. 36, no. 1, pp. 41-48. https://doi.org/10.2337/dc12-1128
Shin, Andrea ; Camilleri, Michael ; Busciglio, Irene ; Burton, Duane ; Stoner, Elizabeth ; Noonan, Patrick ; Gottesdiener, Keith ; Smith, Steven A. ; Vella, Adrian ; Zinsmeister, Alan R. / Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying : Pharmacokinetics and pharmacodynamics. In: Diabetes Care. 2013 ; Vol. 36, No. 1. pp. 41-48.
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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). RESEARCH DESIGN AND 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, HbA1c was 7.2 ± 0.4{\%} (SEM) and total GCSI-DD score was 1.32 ± 0.21. RM-131 accelerated GE t1/2 of solids (P = 0.011); mean difference (Δ) in solid GE t1/2 was 68.3 min (95{\%} CI 20-117) or 66.1{\%}. There were numerical differences in GE lag time, CF6 solids, and GE t1/2 liquids (all P < 0.14). With a signifi cant (P < 0.014) order effect, further analysis of the first treatment period (n = 5 per group) con fi rmed significant RM-131 effects on GE t1/2 (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.",
author = "Andrea Shin and Michael Camilleri and Irene Busciglio and Duane Burton and Elizabeth Stoner and Patrick Noonan and Keith Gottesdiener and Smith, {Steven A.} and Adrian Vella and Zinsmeister, {Alan R.}",
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T1 - Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying

T2 - Pharmacokinetics and pharmacodynamics

AU - Shin, Andrea

AU - Camilleri, Michael

AU - Busciglio, Irene

AU - Burton, Duane

AU - Stoner, Elizabeth

AU - Noonan, Patrick

AU - Gottesdiener, Keith

AU - Smith, Steven A.

AU - Vella, Adrian

AU - Zinsmeister, Alan R.

PY - 2013/1

Y1 - 2013/1

N2 - 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). RESEARCH DESIGN AND 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, HbA1c was 7.2 ± 0.4% (SEM) and total GCSI-DD score was 1.32 ± 0.21. RM-131 accelerated GE t1/2 of solids (P = 0.011); mean difference (Δ) in solid GE t1/2 was 68.3 min (95% CI 20-117) or 66.1%. There were numerical differences in GE lag time, CF6 solids, and GE t1/2 liquids (all P < 0.14). With a signifi cant (P < 0.014) order effect, further analysis of the first treatment period (n = 5 per group) con fi rmed significant RM-131 effects on GE t1/2 (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.

AB - 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). RESEARCH DESIGN AND 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, HbA1c was 7.2 ± 0.4% (SEM) and total GCSI-DD score was 1.32 ± 0.21. RM-131 accelerated GE t1/2 of solids (P = 0.011); mean difference (Δ) in solid GE t1/2 was 68.3 min (95% CI 20-117) or 66.1%. There were numerical differences in GE lag time, CF6 solids, and GE t1/2 liquids (all P < 0.14). With a signifi cant (P < 0.014) order effect, further analysis of the first treatment period (n = 5 per group) con fi rmed significant RM-131 effects on GE t1/2 (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.

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