Selective 5-HT4 Receptor Agonist and Proton Pump Inhibitor (PPI) in Subjects With Gastroesophageal Reflux Disease (GERD)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Shire
ClinicalTrials.gov Identifier:
NCT01472939
First received: November 14, 2011
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
Gastroesophageal Reflux Disease
Drug: SSP-002358 (0.1 mg) + PPI
Drug: SSP-002358 (0.5 mg) + PPI
Drug: SSP-002358 (2.0 mg) + PPI
Drug: Placebo + PPI
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Shire:

Primary Outcome Measures:
  • Change From Baseline in Percent Regurgitation-Free Days Over Weeks 5-8 [ Time Frame: Baseline and over weeks 5-8 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change From Baseline in Heartburn-Free Days Over Weeks 5-8 [ Time Frame: Baseline and over weeks 5-8 ] [ Designated as safety issue: No ]
  • Change From Baseline in the Persistent Reflux Integrated Symptom Measurement (PRISM) Liquid and Food Domain Scores Over Weeks 5-8 [ Time Frame: Baseline and over weeks 5-8 ] [ Designated as safety issue: No ]
    PRISM is a 21 item patient-reported outcome instrument with 4 domains. Items are scored using various scales. Total score ranges from 0-100. Higher scores indicate more severe or frequent symptoms.

  • Area Under the Steady-state Plasma Concentration-time Curve (AUC) of SSP-002358 [ Time Frame: Over 8 hours post-dose (week 2 or later) ] [ Designated as safety issue: No ]
    Area under the plasma concentration versus time curve can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure how much and how long a drug stays in a body.

  • Steady State Maximum Plasma Concentration (Cmax) of SSP-002358 [ Time Frame: Over 8 hours post-dose (week 2 or later) ] [ Designated as safety issue: No ]
    Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administered.

  • Time to Maximum Plasma Concentration (Tmax) of SSP-002358 [ Time Frame: Over 8 hours post-dose (week 2 or later) ] [ Designated as safety issue: No ]

Enrollment: 480
Study Start Date: February 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: SSP-002358 (0.1 mg) + Proton Pump Inhibitor (PPI) Drug: SSP-002358 (0.1 mg) + PPI
0.1 mg tablet three times daily (t.i.d.) taken in addition to a PPI
Other Name: SPD557
Active Comparator: SSP-002358 (0.5 mg) + PPI Drug: SSP-002358 (0.5 mg) + PPI
0.5 mg tablet t.i.d. taken in addition to a PPI
Active Comparator: SSP-002358 (2.0 mg) + PPI Drug: SSP-002358 (2.0 mg) + PPI
2.0 mg tablet t.i.d. taken in addition to a PPI
Placebo Comparator: Placebo + PPI Drug: Placebo + PPI
Placebo t.i.d. taken in addition to a PPI

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written Informed Consent Form signed voluntarily before the first study-related activity.
  2. Aged between 18 and 70 years, inclusive.
  3. Subjects with a history of the cardinal symptoms of GERD (both heartburn and regurgitation) prior to PPI therapy.
  4. Subjects with symptoms of GERD for at least 6 months prior to the Screening Visit.
  5. Subjects who have persistent symptoms of regurgitation for 3 or more days over the past week with or without heartburn while on PPI.
  6. Subjects have at least some improvement to the symptom of heartburn while on PPI therapy.
  7. Subjects on PPI therapy for at least 8 weeks prior to the Screening Visit of which the last 4 weeks are on a stable labeled dose for any GERD indication according to the country label, where a change of PPI therapy would not impact the symptoms (twice-daily dosing of PPI is not allowed in the last 4 weeks)

Exclusion Criteria:

  1. Subjects who show no response to heartburn while on PPI therapy.
  2. Subjects with dyspepsia symptoms that are more predominant than their GERD symptoms (heartburn and/or regurgitation).
  3. Subjects with prior endoscopic anti-reflux procedure or major GI surgery or subjects with major GI disorders.
  4. Presence of severe and clinically uncontrolled cardiovascular, liver, lung or neurologic disease, cancer or AIDS.
  5. Alarm symptoms suggestive of malignancies or organic disease.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01472939

  Show 88 Study Locations
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Nicholas Shaheen, MD, MPH Coordinating/Study PI
  More Information

No publications provided

Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT01472939     History of Changes
Other Study ID Numbers: SPD557-206, 2011-004388-62
Study First Received: November 14, 2011
Results First Received: March 4, 2014
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Gastroesophageal Reflux
Esophageal Motility Disorders
Deglutition Disorders
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014