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

• Study Type: Interventional
• Enrollment (Actual): 609
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Nova Scotia
    • Bridgewater, Nova Scotia, Canada, B4V 3K9
      • Hughie Fraser, MD
    • Bridgewater, Nova Scotia, Canada, B4V 3K9
      • Viable Clinical Research
  • Ontario
    • Vaughan, Ontario, Canada, L4L 4Y7
      • Toronto Digestive Disease Associates Inc
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Dothan, Alabama, United States, 36305
      • Digestive Health Specialists of the Southeast
  • Arizona
    • Peoria, Arizona, United States, 85381
      • Holland Center for Family Health
    • Peoria, Arizona, United States, 85381
      • Hope Research Institute LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners
    • Little Rock, Arkansas, United States, 72209
      • Atria Clinical Research
  • California
    • Canoga Park, California, United States, 91303
      • Hope Clinical Research, LLC
    • Lancaster, California, United States, 93534
      • Om Research LLC
    • Lomita, California, United States, 90717
      • Torrance Clinical Research
    • Murrieta, California, United States, 92563
      • United Gastroenterologists
    • San Diego, California, United States, 92103
      • Clinical Applications Laboratories Inc
    • San Pablo, California, United States, 94806
      • Care Access Research, San Pablo
    • Santa Ana, California, United States, 92703
      • Paragon Rx Clinical, Inc. - Santa Ana
  • Connecticut
    • Hamden, Connecticut, United States, 06518
      • Medical Research Center of Connecticut LLC
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine
    • Stamford, Connecticut, United States, 06905
      • Stamford Therapeutics Consortium
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Optimus U Corp
    • Inverness, Florida, United States, 34452
      • Nature Coast Clinical Research LLC - ERN-PPDS
    • Jacksonville, Florida, United States, 32207
      • Jacksonville Center for Clinical Research
    • Lauderdale Lakes, Florida, United States, 33319
      • Precision Clinical Research, LLC
    • Miami, Florida, United States, 33135
      • Suncoast Research Group LLC - ERN-PPDS
    • Miami, Florida, United States, 33155
      • AppleMed Research Inc
    • Orlando, Florida, United States, 32807
      • Gutierrez Medical Center
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Columbus Regional Research Institute at Talbotton
    • Decatur, Georgia, United States, 30034
      • Consultative Gastroenterology
    • Roswell, Georgia, United States, 30075
      • Atlanta Center For Clinical Research
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta - ERN-PPDS
  • Illinois
    • Gurnee, Illinois, United States, 60041
      • IL Gastroenterology Group
    • Hines, Illinois, United States, 60141
      • Edward Hines Jr VA Hospital - NAVREF
  • Indiana
    • New Albany, Indiana, United States, 47150
      • Aquiant Research
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Kansas Medical Clinic
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates LLC
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Gastroenterology Associates LLC
    • Baton Rouge, Louisiana, United States, 70809
      • Texas Digestive Disease Consultants
    • West Monroe, Louisiana, United States, 71291
      • Clinical Trials of America LA LLC
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Investigative Clinical Research
    • Elkridge, Maryland, United States, 21075
      • Centennial Medical Group
  • Massachusetts
    • Brockton, Massachusetts, United States, 02302
      • Commonwealth Clinical Studies LLC
  • Michigan
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of Western Michigan, PLC
    • Wyoming, Michigan, United States, 49519
      • Gastroenterology Associates of West Michigan
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Gastrointestinal Associates PA
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center - NAVREF
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Digestive Disease Specialists
    • Las Vegas, Nevada, United States, 89128
      • Office of Michael Zimmerman, MD
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Morristown Medical Center
  • New York
    • Bronx, New York, United States, 10468
      • Advantage Clinical Trials
    • Brooklyn, New York, United States, 11235
      • NYScientific
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group LLP
    • Johnson City, New York, United States, 13790
      • United Health Services Hospitals
    • Syracuse, New York, United States, 13210
      • Syracuse VA Medical Center - NAVREF
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates PA
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Medical Center
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • Carolina Digestive Diseases
    • Mount Airy, North Carolina, United States, 27030
      • Clinical Trials of America-NC, LLC
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury LLC
    • Wilmington, North Carolina, United States, 28403
      • Trial Management Associates LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45224
      • Hightop Medical Research Center
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43214
      • Remington Davis Inc
    • Dayton, Ohio, United States, 45440
      • Dayton Gastroenterology Inc
    • Franklin, Ohio, United States, 45005
      • Prestige Clinical Research
  • Oklahoma
    • Norman, Oklahoma, United States, 73071
      • Central Sooner Research
    • Oklahoma City, Oklahoma, United States, 73104
      • The University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute - ERN-PPDS
  • Oregon
    • Portland, Oregon, United States, 97210
      • Northwest Gastroenterology Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15243
      • Research Protocol Management Specialists
    • Pittsburgh, Pennsylvania, United States, 15241
      • Research Protocol Management Specialists
    • Sayre, Pennsylvania, United States, 18840
      • Guthrie Research Institute
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Omega Medical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina - ClinEdge - PPDS
    • Charleston, South Carolina, United States, 29412
      • Pharmacorp Clinical Trials Incorporated
    • Greenville, South Carolina, United States, 29615
      • Gastroenterology Associates, PA
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
    • North Charleston, South Carolina, United States, 29406
      • Clinical Trials of South Carolina
  • Tennessee
    • Franklin, Tennessee, United States, 37067
      • Franklin Gastroenterology
    • Jackson, Tennessee, United States, 38305
      • Clinical Research Solutions PC
    • Nashville, Tennessee, United States, 37211
      • QUALITY Medical Research - Interspond - PPDS
  • Texas
    • Baytown, Texas, United States, 77521
      • Inquest Clinical Research
    • Carrollton, Texas, United States, 75007
      • Texas Health Physicians Group
    • Cypress, Texas, United States, 77429
      • Northside Gastroenterology
    • El Paso, Texas, United States, 79905
      • Texas Tech University Health Sciences Center
    • Houston, Texas, United States, 77079
      • Houston Endoscopy and Research Center
    • Houston, Texas, United States, 77025
      • Kelsey Research Foundation
    • Houston, Texas, United States, 77089
      • Coastal Medical Group
    • San Antonio, Texas, United States, 78229
      • San Antonio Gastroenterology Associates Clinical Trials (SAGACT PLLC)
  • Utah
    • Salt Lake City, Utah, United States, 84124
      • Care Access Research
    • Salt Lake City, Utah, United States, 84132-2101
      • University of Utah Health Sciences Center
    • Salt Lake City, Utah, United States, 84132-2101
      • University of Utah Hospital
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research - Gut Whisperer- ERN-PPDS
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
    • Reston, Virginia, United States, 22191
      • The Gastroenterology Group
    • Richmond, Virginia, United States, 23220
      • Clinical Research Partners Llc
    • Richmond, Virginia, United States, 23235
      • Clinical Research Partners Llc
  • Wisconsin
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center Summit
    • Waukesha, Wisconsin, United States, 53186
      • Aurora Health Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 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; 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; 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, Ironwood Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2018
• Primary Completion (Actual): July 28, 2020
• Study Completion (Actual): November 6, 2020

Study Registration Dates

• First Submitted: June 7, 2018
• First Submitted That Met QC Criteria: June 18, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 18, 2021
• Last Update Submitted That Met QC Criteria: July 23, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: GERD; Gastroesophageal Reflux Disease; Proton Pump Inhibitor; 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: C3718-302

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