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

Michael Camilleri, Richard W McCallum, Jan Tack, Sharon C Spence, Keith Gottesdiener, Fred T Fiedorek, Michael Camilleri, Richard W McCallum, Jan Tack, Sharon C Spence, Keith Gottesdiener, Fred T Fiedorek

Abstract

Background & aims: Gastroparesis is a complication of diabetes with few treatment options. Relamorelin (also referred to as RM-131) is a selective, prokinetic agonist of ghrelin. We aimed to evaluate the 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 minutes 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 with 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 with 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 μg 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 with placebo, accelerated GE, and was generally safe and well tolerated. ClinicalTrials.gov Identifier: NCT02357420.

Keywords: Bloating; Fullness; Nausea; Vomiting.

Conflict of interest statement

Conflicts of Interest: Ms. Spence is a consultant with Motus. Drs. Gottesdiener and Fiedorek are employees and have equity interest in Motus, a prior subsidiary of Rhythm Pharmaceuticals. The other authors have no conflicts of interest.

Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1
Figure 1
A. Experimental design PRO=Patient reported outcome diary; GEBT=gastric emptying breath test; Sx=symptom; Rx=treatment; QD=once daily; BID=twice daily B. CONSORT flow chart
Figure 2
Figure 2
A. Change from baseline through week 12 in DGSSD [4-symptom (nausea, postprandial fullness, abdominal pain, bloating) composite score in total numeric points; full analysis set]. Note that the * and † symbols reflect differences relative to placebo treatment. B. Change from baseline through week 12 for each individual symptom. Note that the * and † symbols reflect differences relative to placebo treatment.

Source: PubMed

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