Relamorelin Relieves Constipation and Accelerates Colonic Transit in a Phase 2, Placebo-Controlled, Randomized Trial

Acosta, Andrés; Camilleri, Michael; Kolar, Gururaj J.; Iturrino, Johanna; Szarka, Lawrence A.; Boldingh, Amy; Burton, Duane D.; Ryks, Michael; Rhoten, Deborah; Zinsmeister, Alan R.; Spence, Sharon; Gottesdiener, Keith; Bouras, Ernest P.; Vázquez-Roque, María I.

doi:10.1016/j.cgh.2015.04.184

Cited by 44 publications

(36 citation statements)

References 27 publications

(37 reference statements)

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“…This finding of mild diarrhea is not surprising, given prior observations of the presence of ghrelin receptors in the enteric neural control of the colon, 39 as well as the relief of constipation and acceleration of colonic transit with relamorelin in patients with chronic constipation. 40 …”

Section: Discussionmentioning

confidence: 99%

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

Camilleri

McCallum

Tack³

et al. 2017

Gastroenterology

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134

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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.

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Section: Discussionmentioning

confidence: 99%

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

Camilleri

McCallum

Tack³

et al. 2017

Gastroenterology

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134

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“…The required sample size was estimated via prospective power analysis. The sample size was calculated based on previous published studies on enterokinetic agents that improved the CTT . Based on previous data, we hypothesized that DA‐9701, when used to treat patients with constipation, would decrease the CTT compared with before treatment .…”

Section: Methodsmentioning

confidence: 99%

DA‐9701 improves colonic transit time and symptoms in patients with functional constipation: A prospective study

Kim

Woo

Kim

et al. 2017

J of Gastro and Hepatol

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“…The safety and efficacy of relamorelin on chronic constipation have also been evaluated. In a Phase II clinical trial, relamorelin significantly reduced the symptoms of constipation and accelerated colonic transit in female patients with chronic constipation . Furthermore, the same study showed that relamorelin rapidly increased colonic contractions without any change in background irregular contractions .…”

Section: Results Of Major Clinical Trials and Current Statusmentioning

confidence: 86%

Growth hormone secretagogues: history, mechanism of action, and clinical development

Ishida

Saitoh

Ebner

et al. 2020

JCSM Rapid Communications

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Growth hormone secretagogues (GHSs) are a generic term to describe compounds that increase growth hormone (GH) release. GHSs include agonists of the growth hormone secretagogue receptor (GHS‐R), whose natural ligand is ghrelin, and agonists of the growth hormone‐releasing hormone (GHRH) receptor, to which the GHRH binds as a native ligand. Several GHSs have been developed with a view to treating or diagnosing of GH deficiency, which causes growth retardation, gastrointestinal dysfunction, and altered body composition, in parallel with extensive research to identify GHRH, GHS‐R, and ghrelin. This review will focus on the research history and the pharmacology of each GHS, which reached randomized clinical trials. Furthermore, we will highlight the publicly disclosed clinical trials regarding GHSs.

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Relamorelin Relieves Constipation and Accelerates Colonic Transit in a Phase 2, Placebo-Controlled, Randomized Trial

Abstract: Relamorelin acts in the colon to significantly reduce symptoms of constipation and accelerate CT in patients with chronic constipation, compared with placebo. ClinicalTrial.Gov registration number: NCT01781104.

Cited by 44 publications

References 27 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

DA‐9701 improves colonic transit time and symptoms in patients with functional constipation: A prospective study

Growth hormone secretagogues: history, mechanism of action, and clinical development

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