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CompletedNCT01472939Updated Jun 9, 2021Results posted

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

A Phase 2 interventional study of SSP-002358 (0.1 mg) + PPI and SSP-002358 (0.5 mg) + PPI in Gastroesophageal Reflux Disease, sponsored by Shire. Completed at 88 sites in 6 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2021-06-09.

Sponsored by Shire · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
480
Allocation
Randomized
Ages
18 Years to 70 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Gastroesophageal Reflux Disease
03

In context

Gastroesophageal Reflux

1,067 studies on the registry are indexed under Gastroesophageal Reflux; 188 are open to participants now.

This study's enrollment of 480 is above the median of 72 across 712 interventional studies indexed under Gastroesophageal Reflux.

Browse Gastroesophageal Reflux studies →

Lead sponsor

Shire is the lead sponsor of 346 studies on the registry; 2 are open to participants now.

Of its 47 completed or terminated interventional studies of FDA-regulated products, 47 (100%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
480 participants (actual)

Study arms

  • Active comparator
    SSP-002358 (0.1 mg) + Proton Pump Inhibitor (PPI)

    Drug: SSP-002358 (0.1 mg) + PPI

  • Active comparator
    SSP-002358 (0.5 mg) + PPI

    Drug: SSP-002358 (0.5 mg) + PPI

  • Active comparator
    SSP-002358 (2.0 mg) + PPI

    Drug: SSP-002358 (2.0 mg) + PPI

  • Placebo comparator
    Placebo + PPI

    Drug: Placebo + PPI

Interventions

  • DrugSSP-002358 (0.1 mg) + PPI

    0.1 mg tablet three times daily (t.i.d.) taken in addition to a PPI

    Also known as: SPD557

  • DrugSSP-002358 (0.5 mg) + PPI

    0.5 mg tablet t.i.d. taken in addition to a PPI

  • DrugSSP-002358 (2.0 mg) + PPI

    2.0 mg tablet t.i.d. taken in addition to a PPI

  • DrugPlacebo + PPI

    Placebo t.i.d. taken in addition to a PPI

06

What researchers measure

Primary outcomes

  1. Change From Baseline in Percent Regurgitation-Free Days Over Weeks 5-8

    Time frame: Baseline and over weeks 5-8

Secondary outcomes

  1. Change From Baseline in Heartburn-Free Days Over Weeks 5-8

    Time frame: Baseline and over weeks 5-8

  2. Change From Baseline in the Persistent Reflux Integrated Symptom Measurement (PRISM) Liquid and Food Domain Scores Over Weeks 5-8

    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.

    Time frame: Baseline and over weeks 5-8

  3. Area Under the Steady-state Plasma Concentration-time Curve (AUC) of SSP-002358

    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.

    Time frame: Over 8 hours post-dose (week 2 or later)

  4. Steady State Maximum Plasma Concentration (Cmax) of SSP-002358

    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 frame: Over 8 hours post-dose (week 2 or later)

  5. Time to Maximum Plasma Concentration (Tmax) of SSP-002358

    Time frame: Over 8 hours post-dose (week 2 or later)

07

Results

Posted Apr 15, 2014

Participant flow

Participant flow — Overall Study
MilestonePlacebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPI
Started123119119119
Completed10310510899
Not completed20141120
Withdrew: Adverse event37714
Withdrew: Lack of efficacy1001
Withdrew: Lost to follow-up3020
Withdrew: Clinically significant pre-dose ecg0010
Withdrew: Prohibited medication0100
Withdrew: Withdrawal by pi1000
Withdrew: Protocol violation3301
Withdrew: Withdrawal by subject9314

Outcome measures

PrimaryChange From Baseline in Percent Regurgitation-Free Days Over Weeks 5-8
Time frame:
Baseline and over weeks 5-8
Reported as:
Least squares mean · percentage of days
Change From Baseline in Percent Regurgitation-Free Days Over Weeks 5-8
percentage of daysPlacebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPI
Change From Baseline in Percent Regurgitation-Free Days Over Weeks 5-836.96 ± 3.59843.01 ± 3.67844.37 ± 3.66738.79 ± 3.728
Statistical analysis
  • Placebo + PPI vs SSP-002358 0.1mg + PPI · Mixed Models Repeated Measures Analysis · p = 0.128 · Mean difference (final values): 6.06 · 95% CI -1.743 to 13.862
  • Placebo + PPI vs SSP-002358 0.5mg + PPI · Mixed Models Repeated Measures Analysis · p = 0.062 · Mean difference (final values): 7.42 · 95% CI -0.378 to 15.212
  • Placebo + PPI vs SSP-002358 2.0mg + PPI · Mixed Models Repeated Measures Analysis · p = 0.650 · Mean difference (final values): 1.83 · 95% CI -6.100 to 9.765
SecondaryChange From Baseline in Heartburn-Free Days Over Weeks 5-8
Time frame:
Baseline and over weeks 5-8
Reported as:
Least squares mean · percentage of days
Change From Baseline in Heartburn-Free Days Over Weeks 5-8
percentage of daysPlacebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPI
Change From Baseline in Heartburn-Free Days Over Weeks 5-821.76 ± 3.62328.52 ± 3.68630.68 ± 3.68827.47 ± 3.756
Statistical analysis
  • Placebo + PPI vs SSP-002358 0.1mg + PPI · Mixed Models Repeated Measures Analysis · p = 0.102 · Mean difference (final values): 6.75 · 95% CI -1.344 to 14.850
  • Placebo + PPI vs SSP-002358 0.5mg + PPI · Mixed Models Repeated Measures Analysis · p = 0.031 · Mean difference (final values): 8.92 · 95% CI 0.814 to 17.021
  • Placebo + PPI vs SSP-002358 2.0mg + PPI · Mixed Models Repeated Measures Analysis · p = 0.175 · Mean difference (final values): 5.71 · 95% CI -2.540 to 13.957
SecondaryChange From Baseline in the Persistent Reflux Integrated Symptom Measurement (PRISM) Liquid and Food Domain Scores Over Weeks 5-8

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.

Time frame:
Baseline and over weeks 5-8
Reported as:
Least squares mean · units on a scale
Change From Baseline in the Persistent Reflux Integrated Symptom Measurement (PRISM) Liquid and Food Domain Scores Over Weeks 5-8
units on a scalePlacebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPI
Change From Baseline in the Persistent Reflux Integrated Symptom Measurement (PRISM) Liquid and Food Domain Scores Over Weeks 5-8-13.29 ± 1.206-15.77 ± 1.228-16.49 ± 1.235-15.44 ± 1.250
Statistical analysis
  • Placebo + PPI vs SSP-002358 0.1mg + PPI · Mixed Models Repeated Measures Analysis · p = 0.064 · Mean difference (final values): -2.47 · 95% CI -5.087 to 0.141
  • Placebo + PPI vs SSP-002358 0.5mg + PPI · Mixed Models Repeated Measures Analysis · p = 0.017 · Mean difference (final values): -3.20 · 95% CI -5.818 to -0.573
  • Placebo + PPI vs SSP-002358 2.0mg + PPI · Mixed Models Repeated Measures Analysis · p = 0.114 · Mean difference (final values): -2.15 · 95% CI -4.813 to 0.519
SecondaryArea Under the Steady-state Plasma Concentration-time Curve (AUC) of SSP-002358

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.

Time frame:
Over 8 hours post-dose (week 2 or later)
Reported as:
Mean · pg*h/ml
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of SSP-002358
pg*h/mlSSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPI
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of SSP-0023581650 ± 7298352 ± 256442613 ± 4971
SecondarySteady State Maximum Plasma Concentration (Cmax) of SSP-002358

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 frame:
Over 8 hours post-dose (week 2 or later)
Reported as:
Mean · pg/ml
Steady State Maximum Plasma Concentration (Cmax) of SSP-002358
pg/mlSSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPI
Steady State Maximum Plasma Concentration (Cmax) of SSP-002358648 ± 3023374 ± 117517900 ± 3573
SecondaryTime to Maximum Plasma Concentration (Tmax) of SSP-002358
Time frame:
Over 8 hours post-dose (week 2 or later)
Reported as:
Median · hours
Time to Maximum Plasma Concentration (Tmax) of SSP-002358
hoursSSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPI
Time to Maximum Plasma Concentration (Tmax) of SSP-0023585.00 (0.483 to 5.58)5.07 (5.00 to 5.55)4.51 (1.00 to 5.48)

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo + PPI—0/122 (0%)25/122 (20.5%)
SSP-002358 0.1mg + PPI—0/119 (0%)22/119 (18.5%)
SSP-002358 0.5mg + PPI—0/118 (0%)35/118 (29.7%)
SSP-002358 2.0mg + PPI—1/118 (0.8%)45/118 (38.1%)
Most frequent serious events
Most frequent serious events
EventPlacebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPI
Pulmonary hypertensionRespiratory, thoracic and mediastinal disorders0/1220/1190/1181/118
Most frequent other events
Most frequent other events
EventPlacebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPI
DiarrhoeaGastrointestinal disorders8/12212/11919/11832/118
NauseaGastrointestinal disorders4/1227/1195/11812/118
Abdominal painGastrointestinal disorders2/1223/1193/11810/118
HeadacheNervous system disorders4/1221/1197/11810/118
Upper respiratory tract infectionInfections and infestations6/1224/1197/1183/118
Back painMusculoskeletal and connective tissue disorders7/1220/1190/1180/118

Baseline characteristics

Safety Analysis Set was used which consisted of all randomized subjects who took at least 1 dose of investigational product. Three subjects did not receive investigational product, therefore n=477.

Age, Continuous
Age, Continuous(Years)Placebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPITotal
Mean46.2 ± 12.148.8 ± 12.5949.2 ± 12.3147.6 ± 11.347.9 ± 12.11
Age, Customized
Age, Customized(Participants)Placebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPITotal
18 - 4040352932136
41 - 5035233232122
51 - 6541524951193
>65698326
Sex: Female, Male
Sex: Female, Male(Participants)Placebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPITotal
Female74787265289
Male48414653188
Region of Enrollment
Region of Enrollment(Participants)Placebo + PPISSP-002358 0.1mg + PPISSP-002358 0.5mg + PPISSP-002358 2.0mg + PPITotal
CZECH REPUBLIC11114
FRANCE22127
GERMANY544417
HUNGARY31217
LATVIA544417
POLAND677828
ROMANIA988833
UNITED STATES92929291367
08

Study locations

88 sites
  • HOPE Research Institute
    Phoenix, Arizona 85050, United States
  • Genova Clinical Research
    Tucson, Arizona 85704, United States
  • Lynn Institute of the Ozarks
    Little Rock, Arkansas 72205, United States
  • Preferred Research Partners, Inc
    Little Rock, Arkansas 72211, United States
  • Arkansas Gastroenterology
    North Little Rock, Arkansas 72117, United States
  • Anaheim Clinical Trials
    Anaheim, California 92801-2417, United States
  • Southern California Research Institute Medical Group Inc
    Los Angeles, California 90045, United States
  • Medical Center for Clinical Research
    San Diego, California 92108, United States
  • Clinicos
    Colorado Springs, Colorado 80904, United States
  • Connecticut Gastroenterology Institute
    Bristol, Connecticut 06010, United States
  • Stamford Therapeutics Consortium
    Stamford, Connecticut 06905, United States
  • Medical Research Unlimited, LLC
    Aventura, Florida 33180, United States
  • Consultants for Clinical Research of South Florida
    Boynton Beach, Florida 33426, United States
  • PAB Clinical Research
    Brandon, Florida 33511, United States
  • Avail Clinical Research, LLC
    DeLand, Florida 32720, United States
  • S & W Clinical Research
    Fort Lauderdale, Florida 33306, United States
  • Medical Research Unlimited, LLC
    Hialeah, Florida 33012, United States
  • Jupiter Research
    Jupiter, Florida 33458, United States
  • Pines Clinical Research, Inc.
    Pembroke Pines, Florida 33028, United States
  • Radiant Research
    Pinellas Park, Florida 33781, United States
  • Accord Clinical Research, LLC
    Port Orange, Florida 32129, United States
  • Meridien Research
    Saint Petersburg, Florida 33709, United States
  • Gastrointestinal Specialists of GA, PC
    Marietta, Georgia 30060, United States
  • Digestive Research Associates
    Newnan, Georgia 30263, United States
  • Rockford Gastroenterology Associates, Ltd
    Rockford, Illinois 61107, United States
  • Professional Research Network of Kansas, LLC
    Wichita, Kansas 67203, United States
  • Research Integrity
    Owensboro, Kentucky 42303, United States
  • Clinical Trials Management
    Metairie, Louisiana 70006, United States
  • Louisiana Research Center, LLC
    Shreveport, Louisiana 71103, United States
  • Meritus Medical Center
    Hagerstown, Maryland 21742, United States
  • Beacon Clinical Research
    Brockton, Massachusetts 02301, United States
  • Center for Digestive and Liver Diseases
    Mexico, Missouri 65265, United States
  • Clinical Research Group of Montana
    Bozeman, Montana 59718, United States
  • Meridian Clinical Research
    Omaha, Nebraska 68134, United States
  • Clinical Research Center of Nevada
    Las Vegas, Nevada 89104, United States
  • New Jersey Physicians, LLC
    Clifton, New Jersey 07012, United States
  • UNC Hospitals
    Chapel Hill, North Carolina 27599, United States
  • Carolinas Research Associates
    Davidson, North Carolina 28036, United States
  • Cumberland Research Associates
    Fayetteville, North Carolina 28314, United States
  • Vital Research, Inc.
    Greensboro, North Carolina 27408, United States
  • Carolinas Research Associates
    Harrisburg, North Carolina 28075, United States
  • Peters Medical Research
    High Point, North Carolina 27262, United States
  • Wake Research Associates
    Raleigh, North Carolina 27612, United States
  • Prestige Clinical Research
    Franklin, Ohio 45005, United States
  • Oklahoma Foundation for Digestive Research Sciences Center
    Oklahoma City, Oklahoma 73104, United States
  • Family Medical Associates
    Levittown, Pennsylvania 19056, United States
  • Guthrie Clinic, Ltd.
    Sayre, Pennsylvania 18840, United States
  • Omega Medical Research
    Warwick, Rhode Island 02886, United States
  • Meridian Clinical Research
    Dakota Dunes, South Dakota 57049, United States
  • Clinsearch, LLC
    Chattanooga, Tennessee 37421, United States
  • Radiant Research Dallas-North
    Dallas, Texas 75231, United States
  • GI Consultants, P.A.
    Houston, Texas 77034, United States
  • Pasadena Gastroenterology Assoc, dba Digestive Health Center
    Pasadena, Texas 77505, United States
  • Office Based Practitioner
    San Antonio, Texas 78229, United States
  • Advanced Research Institute
    Clinton, Utah 84015, United States
  • Advanced Research Institute
    Logan, Utah 84341, United States
  • Advanced Research Institute
    Ogden, Utah 84405, United States
  • Advanced Research Institute
    Sandy, Utah 84094, United States
  • New River Valley Research Institute
    Christiansburg, Virginia 24073, United States
  • Blue Ridge Medical Center
    Lynchburg, Virginia 24502, United States
  • Ramstad Medical Associates
    Suffolk, Virginia 23435, United States
  • Aurora Wilkinson Medical Clinic
    Summit, Wisconsin 53066, United States
  • Hepato-Gastroenterology HK s.r.o.
    Hradec Kralove, 50012, Czechia
  • Nemocnice Valasske Mezirici a.s.
    Valasske Mezirici, 75742, Czechia
  • Praxis Dr. Andreas Schwittay-Facharzt fuer Innere Medizin
    Bohlen, 4564, Germany
  • Zentrum fur Innere Medizin, Klinikum Garmisch Partenkirchen
    Garmisch Partenkirchen, 82467, Germany
  • Haus der Gesundheit
    Ludwigshafen, 67067, Germany
  • Praxis für Gastroenterologie und fachärztliche Innere Medizin
    Ludwigshafen, 67067, Germany
  • Medizinische Fakultät der Otto-von-Guericke Universität
    Magdeburg, 39120, Germany
  • Gemeinschaftspraxis Dres. Brandt
    Potsdam, 14482, Germany
  • Gemeinschaftspraxis Dres Josef und Wilma Großkopf
    Wallerfing, 94574, Germany
  • Daugavpils Regional Hospital
    Daugavpils, 5417, Latvia
  • Pauls Stradins Clinical University Hospital
    Riga, 1002, Latvia
  • Digestive Disease Centre "Gastro"
    Riga, 1006, Latvia
  • Vidzemes Hospital
    Valmiera, 4201, Latvia
  • NZOZ Specjalistyczne Centrum Gastrologii Gastromed
    Bialystok, 15-351, Poland
  • Centrum Medyczne im Swietego Lukasza Sp. z o.o.
    Czestochowa, 42-202, Poland
  • NZOZ ''Salvia''
    Katowice, 40-772, Poland
  • Centrum Medyczne Szpital sw. Rodziny Sp. z o.o.
    Lodz, 90-302, Poland
  • Gastromed Sp. K. NZOZ
    Lublin, 20-607, Poland
  • Endoskopia Sp. z o.o.
    Sopot, 81-756, Poland
  • NZOZ Vivamed
    Warszawa, 03-580, Poland
  • Lexmedica
    Wroclaw, 53-025, Poland
  • Aktywne Centrum Zdrowia NZOZ ZAWIDAWIE Sp. z o.o.
    Wroclaw, 54-239, Poland
  • Brasov County Hospital
    Brasov, 500326, Romania
  • Centrul Medical Galenus
    Targu-Mures, 540098, Romania
  • Cabinet Particular Policlinic Algomed SRL
    Timisoara, 300002, Romania
  • Policlinica "Dr. Citu" SRL
    Timisoara, 300594, Romania
09

References and documents

Publications

  • Shaheen NJ, Adler J, Dedrie S, Johnson D, Malfertheiner P, Miner P, Meulemans A, Poole L, Tack J, Thielemans L, Troy S, Vakil N, Zerbib F, Ruth M. Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy. Aliment Pharmacol Ther. 2015 Apr;41(7):649-61. doi: 10.1111/apt.13115. Epub 2015 Feb 19. PubMed 25693609 ↗
10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 9, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01472939
Lead sponsor
Shire
Responsible party
Sponsor
First posted
Nov 17, 2011
Start date
Feb 27, 2012
Primary completion
May 14, 2013
Completion
May 14, 2013
Results posted
Apr 15, 2014
Last update
Jun 9, 2021

Study contacts

Study Director
study director · Takeda

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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