Delving into the Latest Updates on Revexepride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

M-0003, SHP-557, SPD 557

+ [2]

Target

5-HT4 receptor

Mechanism

5-HT4 receptor agonists(Serotonin 4 (5-HT4) receptor agonists)

Therapeutic Areas

Digestive System DisordersMouth and Tooth DiseasesOtorhinolaryngologic Diseases

Active Indication-

Inactive Indication

Gastroesophageal Reflux

Originator Organization

Janssen Global Services LLC

Active Organization-

Inactive Organization

Shire Plc

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

Structure

Molecular FormulaC21H32ClN3O4

InChIKeyFOUUNSGQVBGYQM-SUMWQHHRSA-N

CAS Registry219984-49-3

Phase I study to evaluate the excretion of radioactivity, the metabolic profile, pharmacokinetics, safety and tolerability following a single oral administration of [14C] SPD557 in healthy male volunteers aged 18 to 50 years (inclusive).The purpose of this study is to investigate how and how quickly SPD557 or its break down products are excreted by analysing blood, faeces and urine samples collected during the study.

Start Date07 Mar 2013

Sponsor / Collaborator

Shire Plc

NCT01472939 / CompletedPhase 2

A Phase 2b, Double-blind, Randomized, Placebo-controlled, Dose-finding Study to Evaluate Efficacy of a Selective 5-HT4 Receptor Agonist and Proton Pump Inhibitor (PPI) in Subjects With Gastroesophageal Reflux Disease (GERD) With Persistent Regurgitation With or Without Heartburn

The aim of this study is to establish a dose-related effect of a selective 5-HT4 receptor agonist compared to placebo on residual symptoms (regurgitation with or without heartburn) in subjects with GERD who have persistent symptoms while on PPI therapy.

Start Date27 Feb 2012

Sponsor / Collaborator

Shire Plc

NCT01415349 / CompletedPhase 1

A Phase 1, Open-label, Randomized, 2-period Crossover Drug Interaction Study in Healthy Adult Subjects to Evaluate the Effect of the Proton Pump Inhibitor Omeprazole on the Pharmacokinetics of SSP-002358

This is a drug interaction study evaluating whether blood plasma concentrations of SSP-002358-base are altered when SSP-002358 is taken together with omeprazole.

Start Date11 Aug 2011

Sponsor / Collaborator

Shire Plc

100 Clinical Results associated with Revexepride

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100 Translational Medicine associated with Revexepride

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100 Patents (Medical) associated with Revexepride

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6

Literatures (Medical) associated with Revexepride

01 Apr 2016·Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility SocietyQ3 · MEDICINE

Randomized clinical trial: a controlled pilot trial of the 5‐HT₄ receptor agonist revexepride in patients with symptoms suggestive of gastroparesis

Q3 · MEDICINE

Article

Author: Thielemans, L. ; Tack, J. ; Cools, M. ; Rotondo, A. ; Meulemans, A.

Abstract:

Background:

Gastroparesis is a chronic gastric disorder characterized by delayed gastric emptying without mechanical obstruction, and clinical symptoms as postprandial fullness, early satiety, bloating, nausea, vomiting, and abdominal pain. Prokinetic agents are used for the treatment of gastroparesis. Revexepride, a 5‐hydroxytryptamine (serotonin) receptor (5‐HT4R) agonist, could be a good candidate drug for the gastroparesis treatment. Aim: In the current phase II, exploratory, double‐blind, randomized, stratified, placebo‐controlled, repeated dose trial (EudraCT number 2007‐004997‐23), the efficacy on gastrointestinal symptoms and gastric emptying rate, safety, and pharmacokinetic profile of three oral doses of revexepride (0.02, 0.1, and 0.5 mg administered orally t.i.d. for 4 weeks) was evaluated in trial participants (diabetic and non‐diabetic) with upper gastrointestinal tract symptoms suggestive for gastroparesis.

Methods:

Eighty participants, enrolled in four parallel treatment groups, were asked to score their symptom diary data, gastroparesis cardinal symptom index (GCSI), patient assessment of upper gastrointestinal disorders‐symptom severity index (PAGI‐SYM), quality of life questionnaires, and meal‐related symptom score. Gastric emptying rate was evaluated by 13C‐octanoic acid breath test.

Key Results:

The severity of the symptoms assessed by means of GCSI and PAGI‐SYM decreased at Week 2 and decreased further at Week 4 in all treatment groups including placebo, with similar trends in all treatment groups. Quality of life improved in all treatment groups after 4 weeks of treatment. No differences on gastric emptying rate were shown between any of the active treatment groups and placebo. Revexepride was generally safe and well‐tolerated.

Conclusions & Inferences:

Four weeks of revexepride treatment did not improve symptoms or gastric emptying over placebo in patients with symptoms suggestive of gastroparesis.

01 Apr 2015·Alimentary pharmacology & therapeuticsQ1 · MEDICINE

Randomised clinical trial: the 5‐HT4 agonist revexepride in patients with gastro‐oesophageal reflux disease who have persistent symptoms despite PPI therapy

Q1 · MEDICINE

Article

Author: Malfertheiner, P. ; Poole, L. ; Johnson, D. ; Vakil, N. ; Thielemans, L. ; Shaheen, N. J. ; Miner, P. ; Dedrie, S. ; Tack, J. ; Meulemans, A. ; Troy, S. ; Ruth, M. ; Adler, J. ; Zerbib, F.

Summary:

Background:

A substantial proportion of patients with gastro‐oesophageal reflux disease (GERD) have only a partial response to proton pump inhibitor (PPI) therapy. Prokinetic drugs may improve reflux symptoms by enhancing oesophageal motility and gastric emptying.

Aim:

To evaluate the effect of revexepride, a novel prokinetic 5‐hydroxytryptamine type 4 (5‐HT4) receptor agonist, compared with placebo, in patients with GERD who have a partial response to PPIs.

Methods:

A phase 2b, double‐blind, parallel‐group study was conducted, in which patients were randomised to one of three revexepride treatment groups (0.1, 0.5 and 2.0 mg three times daily) or placebo (1:1:1:1 ratio). Daily e‐diary data captured patients' symptoms over an 8‐week treatment period. The primary efficacy outcome was the weekly percentage of regurgitation‐free days in the second half of the study (weeks 5–8).

Results:

In total, 480 patients were randomised and 477 received treatment (mean age 47.9 years; 61% women). The mean percentage of regurgitation‐free days increased from baseline (range, 15.0–18.8%) to week 8 (62.3–70.5%) in all four study arms; however, there were no statistically significant differences in this change between placebo and the three treatment arms. No dose‐dependent relationship in treatment effect was observed for any of the study endpoints. The incidence of treatment‐emergent adverse events (TEAEs) was revexepride dose‐dependent. Only one serious TEAE occurred and none resulted in death.

Conclusions:

Revexepride was no more effective than placebo in controlling regurgitation in patients with GERD symptoms partially responsive to PPIs. Revexepride was well tolerated. ClinicalTrials.gov Identifier: NCT01472939.

01 Feb 2015·Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility SocietyQ3 · MEDICINE

Randomized clinical trial: effect of the 5‐HT₄ receptor agonist revexepride on reflux parameters in patients with persistent reflux symptoms despite PPI treatment

Q3 · MEDICINE

Article

Author: Piessevaux, H. ; Tack, J. ; des Varannes, S. B. ; Rykx, A. ; Ruth, M. ; Bredenoord, A. J. ; Thielemans, L. ; Hoppenbrouwers, M. ; Louis, H. ; Zerbib, F. ; Fox, M. ; Mion, F. ; Meulemans, A. ; Dedrie, S. ; Blondeau, K. ; Borovicka, J.

Abstract:

Background:

Approximately, 20–30% of patients with gastro‐esophageal reflux disease (GERD) experience persistent symptoms despite treatment with proton pump inhibitors (PPIs). These patients may have underlying dysmotility; therefore, targeting gastric motor dysfunction in addition to acid inhibition may represent a new therapeutic avenue. The aim of this study was to assess the pharmacodynamic effect of the prokinetic agent revexepride (a 5‐HT4 receptor agonist) in patients with GERD who have persistent symptoms despite treatment with a PPI.

Methods:

This was a phase II, exploratory, multicenter, randomized, placebo‐controlled, double‐blind, parallel‐group study in patients with GERD who experienced persistent symptoms while taking a stable dose of PPIs (ClinicalTrials.gov identifier: NCT01370863). Patients were randomized to either revexepride (0.5 mg, three times daily) or matching placebo for 4 weeks. Reflux events and associated characteristics were assessed by pH/impedance monitoring and disease symptoms were assessed using electronic diaries and questionnaires.

Key Results:

In total, 67 patients were enrolled in the study. There were no significant differences between study arms in the number, the mean proximal extent or the bolus clearance times of liquid‐containing reflux events. Changes from baseline in the number of heartburn, regurgitation, and other symptom events were minimal for each treatment group and no clear trends were observed.

Conclusions & Inferences:

No clear differences were seen in reflux parameters between the placebo and revexepride groups.

100 Deals associated with Revexepride

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Gastroesophageal Reflux	Phase 2	BE	Shire Plc	02 Dec 2010
Gastroesophageal Reflux	Phase 2	FR	Shire Plc	02 Dec 2010
Gastroesophageal Reflux	Phase 2	DE	Shire Plc	02 Dec 2010
Gastroesophageal Reflux	Phase 2	NL	Shire Plc	02 Dec 2010
Gastroesophageal Reflux	Phase 2	CH	Shire Plc	02 Dec 2010
Gastroesophageal Reflux	Phase 2	GB	Shire Plc	02 Dec 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01786876 (Pubmed \| Drug Des Devel Ther)	Phase 1	-	6	2 mg [<sup>14</sup>C]revexepride	uetkbzhyuq(fhffodjhqv) = lhzfaqfirp odxjbbnpyw (lncwdcctrg, 0.4) View more	-	01 Jan 2016
NCT01472939 (Pubmed \| Aliment Pharmacol Ther)	Phase 2	Gastroesophageal Reflux	480	Revexepride 0.1 mg	zfdzaqrhbe(qwhmhcljdt) = bqagscpexy azefqgtigi (weiqmnjmyt )	Negative	01 Apr 2015
				Revexepride 0.5 mg	zfdzaqrhbe(qwhmhcljdt) = wejwnaxneh azefqgtigi (weiqmnjmyt )
NCT01370863 (Pubmed \| Neurogastroenterol Motil) Manual	Phase 2	Gastroesophageal Reflux	67	revexepride	nepmooztet(pksuddkgfn) = ggroortnro ymfzeovkrk (aqrtlhpkdh ) View more	Negative	01 Feb 2015
				Placebo	nepmooztet(pksuddkgfn) = ycpvepswyl ymfzeovkrk (aqrtlhpkdh ) View more
NCT01472939 (CTgov)	Phase 2	Gastroesophageal Reflux \| Heartburn	480	Placebo + PPI	njtkovmlkl(depqtcqivi) = imliyyangu rpqikwnzsd (lsikxtbply, hebtcodbeq - rttqaevuoa) View more	-	15 Apr 2014
NCT01786876 (CTgov)	Phase 1	-	6	SSP-002358 (Radiolabeled SSP-002358)	zkesoikexy(gthcwxngwi) = vivsetgxie gtcdhouhrq (sglhsakvdn, egdrlttleu - firlcborki) View more	-	27 Mar 2014
				SSP-002358 (Radiolabelled SSP-002358)	fkcbptgqrg(yarggioxyg) = tdertxfurd svpawautyo (vumsuqducu, amsyszmpjx - ouyhkrvghk) View more
NCT01370863 (CTgov)	Phase 2	Gastroesophageal Reflux	67	SPD557 (SPD557)	newkugfees(qerqzyvhhh) = vbeuzrcfku senyjihoqs (egruycqqbw, ggtnnlnghs - pwuuaopdxo) View more	-	07 Jun 2013
				placebo (Placebo)	newkugfees(qerqzyvhhh) = lafnhkagyi senyjihoqs (egruycqqbw, qgpzmgormk - pnjrrqnyyn) View more