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

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Trial of Oral IW-3718 Administered to Patients With Gastroesophageal Reflux Disease While Receiving Proton Pump Inhibitors

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.

Study Overview

• Status: Terminated
• Conditions: Gastroesophageal Reflux Disease (GERD)
• Intervention / Treatment: Drug: IW-3718; Drug: Standard-dose PPIs QD; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 495
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada, G1G 3Y8
    • Recherche Clinique Sigma, Inc.
  • Alberta
    • Edmonton, Alberta, Canada, T5A 4L8
      • ALTA Clinical Research Inc
  • Ontario
    • Oshawa, Ontario, Canada, L1H 3K4
      • Taunton Surgical Centre
    • Richmond Hill, Ontario, Canada, L4B 3P8
      • Digestive Health Clinic
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Vaughan, Ontario, Canada, L4L 4Y7
      • Toronto Digestive Disease Associates Inc
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group
    • Mobile, Alabama, United States, 36608
      • Alabama Medical Group, PC
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
    • Tucson, Arizona, United States, 85712
      • Adobe Clinical Research LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72212
      • Applied Research Center
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials LLC - ERN-PPDS
    • Chula Vista, California, United States, 91910
      • GW Research, Inc.
    • Corona, California, United States, 92879
      • Kindred Medical Institute for Clinical Trials, LLC
    • Mission Hills, California, United States, 91345
      • FACEY Medical Foundation
    • Sacramento, California, United States, 95821
      • Northern California Research Corp
    • San Carlos, California, United States, 94070
      • Digestive Care Center
    • San Diego, California, United States, 92123
      • Medical Associates Research Group, Inc.
    • San Diego, California, United States, 92114
      • Precision Research Institute
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Gastroenterology Associates of Fairfield County
    • Bristol, Connecticut, United States, 06010
      • Connecticut Clinical Research Foundation
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research LLC
  • Florida
    • Clearwater, Florida, United States, 33756
      • West Central Gastroenterology, LLP
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research LLC
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32256
      • Borland Groover Clinic
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic Jacksonville - PPDS
    • Jupiter, Florida, United States, 33458
      • Health Awareness Inc - MRA
    • Miami, Florida, United States, 33125
      • Millennium Clinical Research Inc-Miami
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute, Inc
    • Ocoee, Florida, United States, 34761
      • Legacy Clinical Solutions: Sensible HealthCare, LLC - BTC - PPDS
    • Palm Harbor, Florida, United States, 34684
      • Advanced Gastroenterology Associates, LLC
    • Pembroke Pines, Florida, United States, 33028
      • Pines Clinical Research Inc
    • Pinellas Park, Florida, United States, 33782
      • DMI Research
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Atlanta Center For Gastroenterology PC
    • Macon, Georgia, United States, 31201
      • Gastroenterology Associates Of Central Georgia, LLC
  • Illinois
    • Oak Lawn, Illinois, United States, 60453
      • Avicenna-DM Clinical Research
  • Iowa
    • Clive, Iowa, United States, 50325
      • Iowa Digestive Disease Center
  • Kansas
    • Shawnee Mission, Kansas, United States, 66217
      • West Glen GI
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research Center
  • Louisiana
    • Houma, Louisiana, United States, 70360
      • CroNOLA, LLC.
    • Mandeville, Louisiana, United States, 70471
      • Clinical Trials Management LLC
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21215
      • Alan A Rosen MD PA
    • Frederick, Maryland, United States, 21701
      • Elligo Health Research
    • Hagerstown, Maryland, United States, 21742
      • Meritus Center for Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Minnesota Gastroenterology, P.A.
  • Missouri
    • Chesterfield, Missouri, United States, 63141
      • Clinical Research Professionals
    • Kansas City, Missouri, United States, 64131
      • Kansas City Gastroenterology and Hepatology
  • Nevada
    • Reno, Nevada, United States, 89511
      • Advanced Research Institute - Reno
  • New Jersey
    • Egg Harbor Township, New Jersey, United States, 08234
      • AGA Clinical Research Associates, LLC. - MRA
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Lovelace Scientific Resources Inc
  • New York
    • Great Neck, New York, United States, 11021
      • NYU School of Medicine
    • New York, New York, United States, 10003
      • Beth Israel Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10016
      • Manhattan Medical Research Practice PLLC
    • Orchard Park, New York, United States, 14127
      • Orchard Park Family Practice
  • North Carolina
    • Greensboro, North Carolina, United States, 27405
      • Medication Management LLC
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research, LLC
    • Jacksonville, North Carolina, United States, 28546
      • East Carolina Gastroenterology
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates, LLC
    • Raleigh, North Carolina, United States, 27607
      • Wake Endoscopy Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Consultants For Clinical Research Inc
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43213
      • Aventiv Research, Inc.
    • Mentor, Ohio, United States, 44060
      • Great Lakes Gastroenterology Research, LLC
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Digestive Disease Specialists, Inc.
  • Oregon
    • Portland, Oregon, United States, 97232
      • Legacy Research Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15240
      • Veterans Research Foundation of Pittsburgh - NAVREF
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • Consultants of Gastroenterology
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR - ClinSearch, LLC
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Johnson City, Tennessee, United States, 37601
      • Multi Specialty Clinical Research
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Union City, Tennessee, United States, 38237
      • Advanced Gastroenterology-Union City
  • Texas
    • Dallas, Texas, United States, 75231
      • Dallas VA Medical Center - NAVREF
    • Garland, Texas, United States, 75044
      • Digestive Health Associates of Texas
    • Houston, Texas, United States, 77074
      • Southwest Clinical Trials
    • Houston, Texas, United States, 77043
      • Biopharma Informatic Inc.
    • Houston, Texas, United States, 77084
      • Research Consultants
    • Houston, Texas, United States, 77090
      • Houston Digestive Diseases Clinic
    • Pearland, Texas, United States, 77581
      • Pearland Physicians
    • San Antonio, Texas, United States, 78209
      • Quality Research Inc
    • Southlake, Texas, United States, 76092
      • Texas Digestive Disease Consultants
  • Utah
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research LLC - MRA
  • Virginia
    • Christiansburg, Virginia, United States, 24073
      • New River Valley Research Institute
    • Gainesville, Virginia, United States, 20155
      • GI Associates Gainesville
    • Lynchburg, Virginia, United States, 24502
      • Blue Ridge Medical Research
  • Washington
    • Bellevue, Washington, United States, 98004
      • Washington Gastroenterology
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Mayo Clinic Health System - Franciscan Healthcare - PPDS
    • Milwaukee, Wisconsin, United States, 53215
      • Wisconsin Center for Advanced Research Division of GI Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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.

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
Experimental: 1500 mg IW-3718 BID + PPI; Three 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.	Drug: IW-3718; oral tablet; Drug: Standard-dose PPIs QD; background therapy
Placebo Comparator: Placebo + PPI; Three 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.	Drug: Standard-dose PPIs QD; background therapy; Drug: placebo; oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in WHSS at 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.	Baseline, Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weekly Regurgitation Frequency Score (WRFS) at 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.	Baseline, Week 8
Percentage of Participants Who Were Overall Heartburn Responders During the 8-Week Treatment Period	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	Up to Week 8
Proportion of Heartburn-Free Days During the 8-Week Treatment Period	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	Up to Week 8

Collaborators and Investigators

• Sponsor: Ironwood Pharmaceuticals, Inc.
• Investigators: Study Chair: Mike Shetzline, MD, PhD, Chief Medical Officer

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2018
• Primary Completion (Actual): October 7, 2020
• Study Completion (Actual): November 3, 2020

Study Registration Dates

• First Submitted: June 7, 2018
• First Submitted That Met QC Criteria: June 7, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 19, 2021
• Last Update Submitted That Met QC Criteria: August 17, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: GERD; Gastroesophageal Reflux Disease; Proton Pump Inhibitors; IW-3718
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Gastroenteritis; Intestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophagitis; Peptic Ulcer; Duodenal Diseases; Gastroesophageal Reflux; Esophagitis, Peptic
• Other Study ID Numbers: C3718-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No