Relamorelin Reduces Vomiting Frequency and Severity and Accelerates Gastric Emptying in Adults With Diabetic Gastroparesis

Lembo, Anthony; Camilleri, Michael; McCallum, Richard W.; Sastre, Ramon F.; Breton, Cristian; Spence, Sharon; White, Jeffery; Currie, Michelle; Gottesdiener, Keith; Stoner, Elizabeth

doi:10.1053/j.gastro.2016.03.038

Cited by 120 publications

(107 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This effect was quantified by the decrease in GEBT T½, with results similar to findings evident after 4 weeks of relamorelin treatment in a prior diabetic gastroparesis clinical trial. 21 The difference of >10% over placebo needs to be considered in relation to the relatively low calorie content of the test meal (230 kcal). The robust effects of relamorelin on some diabetic gastroparesis symptoms (particularly nausea, postprandial fullness, bloating and abdominal pain) are consistent with the prokinetic action of relamorelin on gastric emptying.…”

Section: Discussionmentioning

confidence: 99%

“…Pharmacokinetic studies in humans have shown a terminal half-life of ~4.5 hours, though, at highest doses, the terminal half-life was 19.4 hours. 21 Toxicologic studies with relamorelin provide >750-fold safety margins compared with dose exposures reported in clinical trials. In prior pharmacokinetic studies, it was estimated that only 8% of relamorelin is excreted in urine, and pharmacokinetics of relamorelin appears similar in healthy volunteers and patients with diabetes mellitus.…”

Section: Methodsmentioning

confidence: 99%

“…Vomiting frequency was selected for the primary endpoint as a result of the observations in a phase 2A study with relamorelin, which showed significant benefit in patients with vomiting severity rated >0 at baseline. 21 The change from baseline through week 12 was also analyzed using a 4-symptom composite of DGSSD symptoms based on weekly normalized scores for nausea, abdominal pain, postprandial fullness and bloating.…”

Section: Methodsmentioning

confidence: 99%

“…20 In a large phase 2A, randomized, 4-week, controlled trial in patients with diabetic gastroparesis, relamorelin, at a dose of 10 μg b.i.d., significantly accelerated gastric emptying and decreased vomiting by ~60%; in the subgroup of patients with vomiting during the 1-week, run-in period, it decreased other symptoms such as nausea, abdominal pain, bloating and early satiety. 21 Thus, the range of efficacy of relamorelin spans from 10 μg to 100 μg, which was the dose range selected for this study.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study

Camilleri

McCallum

Tack³

et al. 2017

Gastroenterology

Self Cite

134

View full text Add to dashboard Cite

Background & Aims Gastroparesis is a complication of diabetes with few treatment options. Relamorelin (also called RM-131) is a selective, prokinetic agonist of ghrelin. We aimed to evaluate efficacy of relamorelin on symptoms and gastric emptying (GE) in a 12-week, phase 2B study of diabetic patients with moderate to severe gastroparesis symptoms (DG). Methods We performed a study of 393 patients with DG (37.7% male; 9.9% with type 1 diabetes; median age, 58.2 years [range 20–76]; median body mass index, 31.4 kg/m2 [range, 18.2–60.1]; HbA1c level, 7.6%, [range, 5.2–11.0]). All participants had 13C-spirulina GE breath test T1/2 values of 79 min or more (with 89.8% delayed relative to 90th %ile of normal, 85.75 minutes), recent vomiting, and gastroparesis cardinal symptom index-daily diary scores of 2.6 or more. Patients were randomly assigned to groups given placebo (n=104) or relamorelin (10 μg [n=98], 30 μg [n=109], or 100 μg [n=82] twice daily) for 12 weeks, following a 2-week, single-blind, placebo run-in period. Patient-reported outcomes were determined from DG Symptom Severity daily e-diaries, in which patients recorded vomiting frequency and symptom scores (nausea, abdominal pain, postprandial fullness, and bloating) on a 0–10 scale. Endpoints were change from baseline in vomiting frequency, composite DG Symptom Severity score, GE, and safety. We performed longitudinal, mixed-effects model analysis using repeated measures, with baseline and baseline-by-week interaction values as covariates. Results Patients given relamorelin had a 75% reduction in vomiting frequency compared to baseline, but this difference was not significant compared with the placebo group. All 4 symptoms of DG (composite or individual symptoms) were significantly reduced over the 12-week study period in all 3 relamorelin dose groups, compared to the placebo group (all P<.05, based on longitudinal analysis over 12 weeks). Relamorelin significantly accelerated GE from baseline compared with placebo (by 12%, P<.05 for the 10 and 30 μg groups; P=.051 for the 100 μg group). Dose-related worsening of glycemic control was noted in 14.5% of patients who received relamorelin; some required insulin or other diabetes drug dosage adjustments. Conclusions In a phase 2B randomized trial of patients with moderate to severe DG, relamorelin significantly reduced core symptoms of DG and overall composite score compared to placebo, accelerated GE, and was generally safe and well tolerated.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study

Camilleri

McCallum

Tack³

et al. 2017

Gastroenterology

Self Cite

134

View full text Add to dashboard Cite

show abstract

“…Relamorelin is a novel long acting ghrelin agonist with 15–130 fold greater potency than the natural peptide that increases antral contractions in healthy controls and accelerates gastric emptying in type 1 and type 2 diabetics with gastroparesis (91, 92, 93, 94). In a multicenter, 4 week phase 2A trial in 204 diabetics with gastroparesis, relamorelin therapy produced greater gastric emptying acceleration versus placebo with associated decreases in vomiting severity and frequency (95). In 119 patients with baseline reports of vomiting from this study, relamorelin significantly reduced nausea, vomiting, abdominal pain, bloating, and early satiety versus placebo.…”

Section: Medications Used To Treat Nausea and Vomitingmentioning

confidence: 99%

Newest Drugs for Chronic Unexplained Nausea and Vomiting

Hasler

2016

Curr Treat Options Gastro

View full text Add to dashboard Cite

OPINION STATEMENT Chronic unexplained nausea and vomiting (CUNV) refers to a symptom complex defined by nausea and/or vomiting with normal diagnostic testing, including anatomic assessments (including upper endoscopy) and measures of upper gut function (e.g. gastric emptying testing). Nausea and vomiting in this condition are postulated to result from aberrant peripheral or central neurohumoral activity. A substantial subset of patients satisfies this diagnosis as more than half of individuals referred for scintigraphic testing exhibit normal gastric emptying rates. No randomized, placebo-controlled trials of any medication treatment have been performed in CUNV. However, agents with potential therapeutic benefit in CUNV include antiemetic drugs, neuromodulatory treatments which are proposed to act by reducing gastric sensitivity, and medications with prokinetic action to stimulate upper gut propulsion. Recently approved drugs with antiemetic capability include serotonin antagonists with novel modes of delivery and neurokinin antagonists with or without additional serotonergic blocking capabilities. Existing neuroleptics and pain modifying neuromodulatory therapies with fortuitous antiemetic benefits are being considered for their benefits in this disorder. Furthermore, current investigations will define potential therapeutic actions of agents that stimulate gastric emptying via action on gastroduodenal serotonin, motilin, and ghrelin receptors. This current research may broaden the treatment options for refractory cases of unexplained nausea and vomiting.

show abstract

Upper Gastrointestinal Manifestations of Diabetes

Camilleri

2021

Clinical Dilemmas in Diabetes

View full text Add to dashboard Cite

Relamorelin Reduces Vomiting Frequency and Severity and Accelerates Gastric Emptying in Adults With Diabetic Gastroparesis

Cited by 120 publications

References 22 publications

Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study

Efficacy and Safety of Relamorelin in Diabetics With Symptoms of Gastroparesis: A Randomized, Placebo-Controlled Study

Newest Drugs for Chronic Unexplained Nausea and Vomiting

Upper Gastrointestinal Manifestations of Diabetes

Contact Info

Product

Resources

About