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A Trial of IW-3718 for 8 Weeks in Patients With Persistent Gastroesophageal Reflux Disease (GERD) Receiving Proton Pump Inhibitors (PPIs)

Phase 3
Terminated
Conditions
Gastroesophageal Reflux Disease (GERD)
Interventions
Drug: placebo
Drug: IW-3718
Drug: Standard-dose PPIs QD
Registration Number
NCT03561090
Lead Sponsor
Ironwood Pharmaceuticals, Inc.
Brief Summary

The objective of this study is to evaluate the safety and efficacy of IW-3718 administered to patients with GERD who continue to have persistent symptoms, such as heartburn and regurgitation, while receiving once-daily (QD), standard-dose PPIs.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
495
Inclusion Criteria

Each patient must meet all of the following criteria to be eligible for enrollment in this study:

  • Patient is an ambulatory male or female (if female, nonpregnant) and is at least 18 years old at the Screening Visit.
  • Patient has a diagnosis of GERD and reports experiencing GERD symptoms (heartburn or regurgitation) while taking standard PPI therapy.
  • Patient has evidence of pathological acid reflux.
  • Female patients must not be pregnant and must agree to avoid pregnancy for the duration of the study.
  • Patient must comply with study procedures.
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Exclusion Criteria

Patients who meet any of the following criteria will not be eligible to participate in the study:

  • Patient has a history of complete lack of GERD symptom response to PPI therapy.
  • Patient has a significant medical or surgical history including conditions that would impact drug absorption or metabolism (such as bowel obstruction, poorly controlled diabetes, gastroparesis, hiatal hernia).
  • Patient reports pain or burning behind the breastbone or in the center of the upper stomach as his or her predominant symptom at the Screening Visit.
  • Patient has received an investigational drug during the 30 days before the Screening Visit, or is planning to receive another investigational drug or use an investigational device at any time during the study.

NOTE: Other inclusion and exclusion criteria apply, per the study protocol.

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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + PPIplaceboThree placebo tablets administered BID immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
1500 mg IW-3718 BID + PPIStandard-dose PPIs QDThree 500 mg IW-3718 tablets administered twice daily (BID), immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
1500 mg IW-3718 BID + PPIIW-3718Three 500 mg IW-3718 tablets administered twice daily (BID), immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
Placebo + PPIStandard-dose PPIs QDThree placebo tablets administered BID immediately after the morning and evening meals. Standard-dose PPIs administered QD approximately 30-60 minutes before the morning meal each day.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in WHSS at Week 8Baseline, Week 8

The WHSS is defined as the weekly average of the DHSS. The DHSS for a day is the greater of the 2 items assessing heartburn severity (Item #1 "Burning feeling behind the breastbone or in the center of the upper stomach" and Item #2 "Pain behind the breastbone or in the center of the upper stomach"). The DHSS items are assessed on a 5-point ordinal scale, where 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, and 5=Severe; higher scores indicate worse symptoms. A negative change from baseline indicates improvement.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Were Overall Heartburn Responders During the 8-Week Treatment PeriodUp to Week 8

An overall heartburn responder is a participant who is a weekly heartburn responder for at least 4 of the 8 treatment weeks and for at least 1 of the final 2 treatment weeks (i.e., Week 7 and Week 8). A weekly heartburn responder is a participant with a decrease of \>/= 45% from baseline in WHSS. A participant who reported heartburn severity for less than 4 days during a week is not considered a responder for that week.

The WHSS is defined as the weekly average of the DHSS. The DHSS for a day is the greater of the 2 items assessing heartburn severity (Item #1 "Burning feeling behind the breastbone or in the center of the upper stomach" and Item #2 "Pain behind the breastbone or in the center of the upper stomach"). The DHSS items are assessed on a 5-point ordinal scale, where 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, and 5=Severe; higher scores indicate worse symptoms. A negative change from baseline indicates improvement

Change From Baseline in Weekly Regurgitation Frequency Score (WRFS) at Week 8Baseline, Week 8

The WRFS is defined as the average of available daily regurgitation frequency scores (DRFS) during a week. DRFS is defined as the maximum score of the 2 items measuring regurgitation from a particular day (Item #6 "Regurgitation \[liquid or food moving upwards toward your throat or mouth\]" and Item #7 "An acid or bitter taste in the mouth"). The DRFS items are assessed on a 4-point ordinal scale, where 0=Never, 1=Rarely, 2-Sometimes, 3=Often, and 4=Very Often; higher scores indicate worse symptoms. A negative change from baseline indicates improvement.

Proportion of Heartburn-Free Days During the 8-Week Treatment PeriodUp to Week 8

Proportion of heartburn-free days is calculated as the number of heartburn-free (DHSS=0) days divided by the number of diary entry days. The DHSS for a day is the greater of the 2 items assessing heartburn severity (Item #1 "Burning feeling behind the breastbone or in the center of the upper stomach" and Item #2 "Pain behind the breastbone or in the center of the upper stomach"). The DHSS items are assessed on a 5-point ordinal scale, where 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, and 5=Severe; higher scores indicate worse symptoms. A negative change from baseline indicates improvement

Trial Locations

Locations (99)

Advanced Research Institute

🇺🇸

Ogden, Utah, United States

Medication Management LLC

🇺🇸

Greensboro, North Carolina, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

Aventiv Research, Inc.

🇺🇸

Columbus, Ohio, United States

Biopharma Informatic Inc.

🇺🇸

Houston, Texas, United States

Pinnacle Research Group

🇺🇸

Anniston, Alabama, United States

Anaheim Clinical Trials LLC - ERN-PPDS

🇺🇸

Anaheim, California, United States

Northern California Research Corp

🇺🇸

Sacramento, California, United States

Applied Research Center

🇺🇸

Little Rock, Arkansas, United States

Minnesota Gastroenterology, P.A.

🇺🇸

Plymouth, Minnesota, United States

Clinical Research Professionals

🇺🇸

Chesterfield, Missouri, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Stanford University School of Medicine

🇺🇸

Stanford, California, United States

Kindred Medical Institute for Clinical Trials, LLC

🇺🇸

Corona, California, United States

Facey Medical Foundation

🇺🇸

Mission Hills, California, United States

West Central Gastroenterology, LLP

🇺🇸

Clearwater, Florida, United States

Avicenna-DM Clinical Research

🇺🇸

Oak Lawn, Illinois, United States

Alan A Rosen MD PA

🇺🇸

Baltimore, Maryland, United States

Orchard Park Family Practice

🇺🇸

Orchard Park, New York, United States

Borland Groover Clinic

🇺🇸

Jacksonville, Florida, United States

Connecticut Clinical Research Foundation

🇺🇸

Bristol, Connecticut, United States

CroNOLA, LLC.

🇺🇸

Houma, Louisiana, United States

GW Research, Inc.

🇺🇸

Chula Vista, California, United States

Kansas City Gastroenterology and Hepatology

🇺🇸

Kansas City, Missouri, United States

Gastroenterology Associates of Fairfield County

🇺🇸

Bridgeport, Connecticut, United States

Avail Clinical Research LLC

🇺🇸

DeLand, Florida, United States

Mayo Clinic Jacksonville - PPDS

🇺🇸

Jacksonville, Florida, United States

Wake Endoscopy Center

🇺🇸

Raleigh, North Carolina, United States

Consultants of Gastroenterology

🇺🇸

Columbia, South Carolina, United States

Manhattan Medical Research Practice PLLC

🇺🇸

New York, New York, United States

Great Lakes Gastroenterology Research, LLC

🇺🇸

Mentor, Ohio, United States

East Carolina Gastroenterology

🇺🇸

Jacksonville, North Carolina, United States

Cleveland Clinic

🇺🇸

Cleveland, Ohio, United States

Gastro One

🇺🇸

Germantown, Tennessee, United States

Southwest Clinical Trials

🇺🇸

Houston, Texas, United States

Research Consultants

🇺🇸

Houston, Texas, United States

Advanced Gastroenterology-Union City

🇺🇸

Union City, Tennessee, United States

Mayo Clinic Health System - Franciscan Healthcare - PPDS

🇺🇸

La Crosse, Wisconsin, United States

Texas Digestive Disease Consultants

🇺🇸

Southlake, Texas, United States

Digestive Health Associates of Texas

🇺🇸

Garland, Texas, United States

Aspen Clinical Research LLC - MRA

🇺🇸

Orem, Utah, United States

Washington Gastroenterology

🇺🇸

Bellevue, Washington, United States

Precision Research Institute

🇺🇸

San Diego, California, United States

Medical Associates Research Group, Inc.

🇺🇸

San Diego, California, United States

Consultants For Clinical Research Inc

🇺🇸

Cincinnati, Ohio, United States

New River Valley Research Institute

🇺🇸

Christiansburg, Virginia, United States

Digestive Disease Specialists, Inc.

🇺🇸

Oklahoma City, Oklahoma, United States

Vanderbilt University Medical Center

🇺🇸

Nashville, Tennessee, United States

Cotton O'Neil Clinical Research Center

🇺🇸

Topeka, Kansas, United States

West Glen GI

🇺🇸

Shawnee Mission, Kansas, United States

Legacy Research Institute

🇺🇸

Portland, Oregon, United States

Elite Clinical Studies

🇺🇸

Phoenix, Arizona, United States

Digestive Care Center

🇺🇸

San Carlos, California, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

Millennium Clinical Research Inc-Miami

🇺🇸

Miami, Florida, United States

Advanced Research Institute, Inc

🇺🇸

New Port Richey, Florida, United States

Clinical Trials Management LLC

🇺🇸

Mandeville, Louisiana, United States

Clinical Research Institute of Michigan

🇺🇸

Chesterfield, Michigan, United States

Wisconsin Center for Advanced Research Division of GI Associates

🇺🇸

Milwaukee, Wisconsin, United States

Lovelace Scientific Resources Inc

🇺🇸

Albuquerque, New Mexico, United States

AGA Clinical Research Associates, LLC. - MRA

🇺🇸

Egg Harbor Township, New Jersey, United States

Veterans Research Foundation of Pittsburgh - NAVREF

🇺🇸

Pittsburgh, Pennsylvania, United States

Dallas VA Medical Center - NAVREF

🇺🇸

Dallas, Texas, United States

Quality Research Inc

🇺🇸

San Antonio, Texas, United States

Pearland Physicians

🇺🇸

Pearland, Texas, United States

Blue Ridge Medical Research

🇺🇸

Lynchburg, Virginia, United States

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

Toronto Digestive Disease Associates Inc

🇨🇦

Vaughan, Ontario, Canada

Taunton Surgical Centre

🇨🇦

Oshawa, Ontario, Canada

Digestive Health Clinic

🇨🇦

Richmond Hill, Ontario, Canada

Recherche Clinique Sigma, Inc.

🇨🇦

Québec, Canada

Alabama Medical Group, PC

🇺🇸

Mobile, Alabama, United States

University of Colorado Hospital

🇺🇸

Aurora, Colorado, United States

Health Awareness Inc - MRA

🇺🇸

Jupiter, Florida, United States

Legacy Clinical Solutions: Sensible HealthCare, LLC - BTC - PPDS

🇺🇸

Ocoee, Florida, United States

Advanced Gastroenterology Associates, LLC

🇺🇸

Palm Harbor, Florida, United States

Pines Clinical Research Inc

🇺🇸

Pembroke Pines, Florida, United States

DMI Research

🇺🇸

Pinellas Park, Florida, United States

Palm Beach Research Center

🇺🇸

West Palm Beach, Florida, United States

Gastroenterology Associates of Central Georgia, LLC

🇺🇸

Macon, Georgia, United States

Iowa Digestive Disease Center

🇺🇸

Clive, Iowa, United States

Peters Medical Research, LLC

🇺🇸

High Point, North Carolina, United States

Beth Israel Medical Center

🇺🇸

New York, New York, United States

NYU School of Medicine

🇺🇸

Great Neck, New York, United States

Atlanta Center For Gastroenterology PC

🇺🇸

Decatur, Georgia, United States

Wake Research Associates, LLC

🇺🇸

Raleigh, North Carolina, United States

Houston Digestive Diseases Clinic

🇺🇸

Houston, Texas, United States

GI Associates Gainesville

🇺🇸

Gainesville, Virginia, United States

Arkansas Gastroenterology

🇺🇸

North Little Rock, Arkansas, United States

Advanced Research Institute - Reno

🇺🇸

Reno, Nevada, United States

Weill Cornell Medical College

🇺🇸

New York, New York, United States

ALTA Clinical Research Inc

🇨🇦

Edmonton, Alberta, Canada

Tandem Clinical Research, LLC

🇺🇸

Marrero, Louisiana, United States

Meritus Center For Clinical Research

🇺🇸

Hagerstown, Maryland, United States

WR - ClinSearch, LLC

🇺🇸

Chattanooga, Tennessee, United States

Adobe Clinical Research LLC

🇺🇸

Tucson, Arizona, United States

Elligo Health Research

🇺🇸

Frederick, Maryland, United States

Chase Medical Research LLC

🇺🇸

Waterbury, Connecticut, United States

Multi Specialty Clinical Research

🇺🇸

Johnson City, Tennessee, United States

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