An Explorative Trial to Evaluate the Pharmacodynamic Effect of SPD557 on Reflux Parameters in Refractory GERD Patients

An Explorative, Randomized, Placebo-controlled, DB, Parallel-group Trial, to Evaluate the Pharmacodynamic Effect of SPD557 on Reflux Parameters in Subjects With GERD & With Persistent Symptoms Despite Taking a Stable Dose of PPIs

The purpose of this trial is to investigate the pharmacodynamic effect on reflux parameters of SPD557 tablets (0.5 mg t.i.d., on top of PPI treatment) in patients with Gastroesophageal Reflux Disease (GERD) with persistent symptoms despite taking a stable dose of proton pump inhibitors. Additionally the effect on symptoms will be explored and safety and tolerability will be evaluated.

Study Overview

• Status: Terminated
• Conditions: Gastroesophageal Reflux Disease
• Intervention / Treatment: Drug: SPD557; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires Saint Luc
  • Leuven, Belgium, 3000
    • UZ Leuven, Belgium
  • Bruxelles
    • Brussels, Bruxelles, Belgium, 1070
      • CUB Hôpital Erasme
• France
  • Bordeaux Cedex, France, 33075
    • CHU de Bordeaux - Hopital Saint Andre
  • Lyon, France, 69437
    • CHU de Lyon - Groupement Hospitalier Edouard Herriot
  • Nantes Cedex 1, France, 44093
    • Hôtel Dieu - CHU de Nantes
• Germany
  • Garmisch-Partenkirchen, Germany, 82467
    • Klinikum Garmisch-Partenkirchen GmbH
  • Magdeburg, Germany, 39120
    • Otto-von-Guericke University
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Academisch Medisch Centrum (AMC)
• Switzerland
  • Bern, Switzerland, BHH D140
    • Inselspital Bern (Bern University Hopsital)
  • St. Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen
  • Zurich, Switzerland, CH-8091
    • University Hospital Zurich
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital
  • London, United Kingdom, E12AJ
    • Wingate Institute of Neurogastroenterology
  • Nottingham, United Kingdom, NG7 2UH
    • Queen's Medical Center (Nottingham University Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

1. Written ICF signed voluntarily before the first trial related activity.
2. Subjects with a history of GERD symptoms (i.e., heartburn and/or regurgitation) during the last 6 months
3. Subjects on a stable dose of PPIs, compliant for at least 6 weeks prior to screening.
4. ≥3 days per week with heartburn and/or regurgitation symptoms of at least moderate severity and a minimum of 25 liquid containing reflux events over 24h (pH/MII monitoring).

Exclusion criteria:

1. Subjects with prior endoscopic anti-reflux procedure or major GI surgery or subjects with major GI disorders.
2. Presence of severe and clinically uncontrolled cardiovascular, liver or lung disease, neurologic, cancer or AIDS.
3. Alarm symptoms suggestive of malignancies or organic disease.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; matching placebo tablet t.i.d. for 4 weeks on top of stable PPI treatment
Experimental: SPD557	Drug: SPD557; 0.5 mg tablet t.i.d. for 4 weeks on top of stable PPI treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Number of Liquid-containing Reflux Events (pH/MII Monitoring) at 4 Weeks	This is used to characterize gastric reflux events. The measurements were made over a 24-hour period at baseline and again at week 4.	Baseline and 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Number of Days With Heartburn and/or Regurgitation at 4 Weeks		Baseline and 4 weeks
Change From Baseline in the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) Questionnaire at 4 Weeks	The PAGI-SYM contains 20 items and the scores range from 0 (no symptoms)-5 (very severe symptoms) for each item with a total score of 0-100. Higher scores indicate more severe gastrointestinal symptoms.	Baseline and 4 weeks

Collaborators and Investigators

• Sponsor: Shire

Publications and helpful links

General Publications

• Tack J, Zerbib F, Blondeau K, des Varannes SB, Piessevaux H, Borovicka J, Mion F, Fox M, Bredenoord AJ, Louis H, Dedrie S, Hoppenbrouwers M, Meulemans A, Rykx A, Thielemans L, Ruth M. Randomized clinical trial: effect of the 5-HT4 receptor agonist revexepride on reflux parameters in patients with persistent reflux symptoms despite PPI treatment. Neurogastroenterol Motil. 2015 Feb;27(2):258-68. doi: 10.1111/nmo.12484. Epub 2014 Dec 21.

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2010
• Primary Completion (Actual): May 29, 2012
• Study Completion (Actual): May 29, 2012

Study Registration Dates

• First Submitted: May 31, 2011
• First Submitted That Met QC Criteria: June 9, 2011
• First Posted (Estimate): June 10, 2011

Study Record Updates

• Last Update Posted (Actual): June 10, 2021
• Last Update Submitted That Met QC Criteria: May 29, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: GERD; Gastroesophageal reflux disease; Proton pump inhibitors; SPD557
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux
• Other Study ID Numbers: SPD557-202; 2010-021397-12 (EudraCT Number)