Dataset Information

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

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 ?g [n=98], 30 ?g [n=109], or 100 ?g [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 ?g and 30 ?g groups; P = .051 for the 100 ?g 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.

SUBMITTER: Camilleri M

PROVIDER: S-EPMC5670003 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Camilleri Michael M McCallum Richard W RW Tack Jan J Spence Sharon C SC Gottesdiener Keith K Fiedorek Fred T FT

Gastroenterology 20170729 5

<h4>Background & aims</h4>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).<h4>Methods</h4>We performed a study of 393 patients with DG (37.7% male; 9.9% with type 1 diabetes; median age, 58.2 years [ ...[more]

PMID: 28760384

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Project description:To evaluate the efficacy and safety of lurasidone in acutely symptomatic adolescent patients with schizophrenia.Patients aged 13-17 years were randomly assigned to 6 weeks of double-blind, fixed-dose lurasidone (40 or 80?mg/day) or placebo. Primary and key secondary efficacy measures were change from baseline to week 6 in the Positive and Negative Symptom Scale (PANSS) total score and Clinical Global Impressions-Severity (CGI-S) score, respectively, using mixed model for repeated measurement (MMRM) analysis. The proportion of patients achieving treatment response at endpoint, based on ?20% reduction in PANSS total score, was analyzed using a logistic regression model.Least-squares (LS) mean change in PANSS total score from baseline to week 6 was -18.6 with lurasidone 40?mg/day (N?=?108; p?<?0.001 vs. placebo; effect size?=?0.51), -18.3 with lurasidone 80?mg/day (N?=?106; p?<?0.001 vs. placebo; effect size?=?0.48), and -10.5 with placebo (N?=?112). Similarly, LS mean change in CGI-S score from baseline to week 6 was significantly greater with lurasidone 40?mg/day (-1.0; p?<?0.001; effect size?=?0.49) and 80?mg/day (-0.9; p?=?0.0015; effect size?=?0.45) compared with placebo (-0.5). A significantly higher proportion of patients met responder criteria on lurasidone 40 and 80?mg/day versus placebo (63.9% and 65.1% vs. 42.0%; p?<?0.001 for both comparisons). The rate of study discontinuation was 10.3% in lurasidone-treated and 17.7% in placebo-treated patients. The most common adverse events (incidence ?5% in either lurasidone dose group and at least twice the rate of placebo) for lurasidone 40?mg/day, 80?mg/day, and placebo, respectively, were nausea (12.7%, 14.4%, and 2.7%), somnolence (9.1%, 11.5%, and 5.4%), akathisia (9.1%, 8.7%, and 1.8%), vomiting (8.2%, 6.7%, and 1.8%), and sedation (5.5%, 1.9%, and 1.8%). Treatment with lurasidone was not associated with clinically meaningful effects on body weight, lipids, measures of glycemic control, or prolactin.In this 6-week study, lurasidone at doses of 40 and 80?mg/day demonstrated statistically significant and clinically meaningful symptom improvement in adolescent patients with schizophrenia. Lurasidone was generally well tolerated with few effects on weight and metabolic parameters, consistent with findings in adult patients with schizophrenia.

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Dataset Information

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

Publications

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

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