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

Gastroesophageal Reflux Disease (GERD) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03561090
• Other study ID #: C3718-301
• Status: Terminated
• Phase: Phase 3
• Start date: June 20, 2018
• Est. completion date: November 3, 2020

Study information

• Verified date: August 2021
• Source: Ironwood Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 495
• Est. completion date: November 3, 2020
• Est. primary completion date: October 7, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Esophagitis, Peptic
• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease (GERD)

Intervention

Drug:
• IW-3718
oral tablet
• placebo
oral tablet
• Standard-dose PPIs QD
background therapy

Locations

Country	Name	City	State
Canada	ALTA Clinical Research Inc	Edmonton	Alberta
Canada	Taunton Surgical Centre	Oshawa	Ontario
Canada	Recherche Clinique Sigma, Inc.	Québec
Canada	Digestive Health Clinic	Richmond Hill	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
Canada	Toronto Digestive Disease Associates Inc	Vaughan	Ontario
United States	Lovelace Scientific Resources Inc	Albuquerque	New Mexico
United States	Anaheim Clinical Trials LLC - ERN-PPDS	Anaheim	California
United States	Pinnacle Research Group	Anniston	Alabama
United States	University of Colorado Hospital	Aurora	Colorado
United States	Alan A Rosen MD PA	Baltimore	Maryland
United States	Washington Gastroenterology	Bellevue	Washington
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Gastroenterology Associates of Fairfield County	Bridgeport	Connecticut
United States	Connecticut Clinical Research Foundation	Bristol	Connecticut
United States	WR - ClinSearch, LLC	Chattanooga	Tennessee
United States	Clinical Research Institute of Michigan	Chesterfield	Michigan
United States	Clinical Research Professionals	Chesterfield	Missouri
United States	New River Valley Research Institute	Christiansburg	Virginia
United States	GW Research, Inc.	Chula Vista	California
United States	Consultants For Clinical Research Inc	Cincinnati	Ohio
United States	West Central Gastroenterology, LLP	Clearwater	Florida
United States	Cleveland Clinic	Cleveland	Ohio
United States	Iowa Digestive Disease Center	Clive	Iowa
United States	Consultants of Gastroenterology	Columbia	South Carolina
United States	Aventiv Research, Inc.	Columbus	Ohio
United States	Kindred Medical Institute for Clinical Trials, LLC	Corona	California
United States	Dallas VA Medical Center - NAVREF	Dallas	Texas
United States	Atlanta Center For Gastroenterology PC	Decatur	Georgia
United States	Avail Clinical Research LLC	DeLand	Florida
United States	AGA Clinical Research Associates, LLC. - MRA	Egg Harbor Township	New Jersey
United States	Elligo Health Research	Frederick	Maryland
United States	GI Associates Gainesville	Gainesville	Virginia
United States	University of Florida	Gainesville	Florida
United States	Digestive Health Associates of Texas	Garland	Texas
United States	Gastro One	Germantown	Tennessee
United States	NYU School of Medicine	Great Neck	New York
United States	Medication Management LLC	Greensboro	North Carolina
United States	Meritus Center For Clinical Research	Hagerstown	Maryland
United States	Peters Medical Research, LLC	High Point	North Carolina
United States	CroNOLA, LLC.	Houma	Louisiana
United States	Biopharma Informatic Inc.	Houston	Texas
United States	Houston Digestive Diseases Clinic	Houston	Texas
United States	Research Consultants	Houston	Texas
United States	Southwest Clinical Trials	Houston	Texas
United States	Borland Groover Clinic	Jacksonville	Florida
United States	East Carolina Gastroenterology	Jacksonville	North Carolina
United States	Mayo Clinic Jacksonville - PPDS	Jacksonville	Florida
United States	Multi Specialty Clinical Research	Johnson City	Tennessee
United States	Health Awareness Inc - MRA	Jupiter	Florida
United States	Kansas City Gastroenterology and Hepatology	Kansas City	Missouri
United States	Mayo Clinic Health System - Franciscan Healthcare - PPDS	La Crosse	Wisconsin
United States	Applied Research Center	Little Rock	Arkansas
United States	Blue Ridge Medical Research	Lynchburg	Virginia
United States	Gastroenterology Associates of Central Georgia, LLC	Macon	Georgia
United States	Clinical Trials Management LLC	Mandeville	Louisiana
United States	Tandem Clinical Research, LLC	Marrero	Louisiana
United States	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio
United States	Millennium Clinical Research Inc-Miami	Miami	Florida
United States	Wisconsin Center for Advanced Research Division of GI Associates	Milwaukee	Wisconsin
United States	Facey Medical Foundation	Mission Hills	California
United States	Alabama Medical Group, PC	Mobile	Alabama
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Advanced Research Institute, Inc	New Port Richey	Florida
United States	Beth Israel Medical Center	New York	New York
United States	Manhattan Medical Research Practice PLLC	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Arkansas Gastroenterology	North Little Rock	Arkansas
United States	Avicenna-DM Clinical Research	Oak Lawn	Illinois
United States	Legacy Clinical Solutions: Sensible HealthCare, LLC - BTC - PPDS	Ocoee	Florida
United States	Advanced Research Institute	Ogden	Utah
United States	Digestive Disease Specialists, Inc.	Oklahoma City	Oklahoma
United States	Orchard Park Family Practice	Orchard Park	New York
United States	Aspen Clinical Research LLC - MRA	Orem	Utah
United States	Advanced Gastroenterology Associates, LLC	Palm Harbor	Florida
United States	Pearland Physicians	Pearland	Texas
United States	Pines Clinical Research Inc	Pembroke Pines	Florida
United States	Elite Clinical Studies	Phoenix	Arizona
United States	DMI Research	Pinellas Park	Florida
United States	Veterans Research Foundation of Pittsburgh - NAVREF	Pittsburgh	Pennsylvania
United States	Minnesota Gastroenterology, P.A.	Plymouth	Minnesota
United States	Legacy Research Institute	Portland	Oregon
United States	Wake Endoscopy Center	Raleigh	North Carolina
United States	Wake Research Associates, LLC	Raleigh	North Carolina
United States	Advanced Research Institute - Reno	Reno	Nevada
United States	Northern California Research Corp	Sacramento	California
United States	Quality Research Inc	San Antonio	Texas
United States	Digestive Care Center	San Carlos	California
United States	Medical Associates Research Group, Inc.	San Diego	California
United States	Precision Research Institute	San Diego	California
United States	West Glen GI	Shawnee Mission	Kansas
United States	Texas Digestive Disease Consultants	Southlake	Texas
United States	Stanford University School of Medicine	Stanford	California
United States	Cotton O'Neil Clinical Research Center	Topeka	Kansas
United States	Adobe Clinical Research LLC	Tucson	Arizona
United States	Advanced Gastroenterology-Union City	Union City	Tennessee
United States	Chase Medical Research LLC	Waterbury	Connecticut
United States	Palm Beach Research Center	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Ironwood Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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