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

62 Citations (Scopus)

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

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, 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.
@article{5cf1154a1264406594bdf56f0684d090,
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). 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.}",
year = "2013",
month = "1",
doi = "10.2337/dc12-1128",
language = "English (US)",
volume = "36",
pages = "41--48",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "1",

}

TY - JOUR

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.

UR - http://www.scopus.com/inward/record.url?scp=84872040988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872040988&partnerID=8YFLogxK

U2 - 10.2337/dc12-1128

DO - 10.2337/dc12-1128

M3 - Article

VL - 36

SP - 41

EP - 48

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 1

ER -