A Trial of IW-3718 for 8 Weeks in Patients With Symptomatic Gastroesophageal Reflux Disease (GERD)

Gastroesophageal Reflux Disease Clinical Trial

Official title:

A Phase 2b, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-range-finding Trial of IW-3718 Administered Orally for 8 Weeks to Patients With Symptomatic Gastroesophageal Reflux Disease Not Completely Responsive to Proton Pump Inhibitors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02637557
• Other study ID #: ICP-3718-202
• Status: Completed
• Phase: Phase 2
• Start date: March 1, 2016
• Est. completion date: April 26, 2017

Study information

• Verified date: October 2019
• Source: Ironwood Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of this study are to evaluate the safety, efficacy, and dose-response relationship of IW-3718 administered orally to participants who have GERD and continue to experience GERD symptoms while receiving once-daily (QD), standard-dose proton pump inhibitors (PPIs).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: April 26, 2017
• Est. primary completion date: April 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient is an ambulatory, community-dwelling male or nonpregnant female and is at least 18 years old at the Screening Visit. Lactating females must agree not to breastfeed.

• Patient has a diagnosis of GERD and reports experiencing GERD symptoms (heartburn or regurgitation) on = 4 days per week during the 8 weeks before the Screening Visit while taking standard QD PPI therapy.

Exclusion Criteria:

• Patient may not meet any of the excluded conditions specified in the protocol

• Patient has any alarm symptoms including but not limited to GI bleeding, anemia, vomiting, dysphagia, or unexpected weight loss any time during the Screening or Pretreatment Periods

• Patient has a history of clinically significant hypersensitivity or allergies to any of the excipients contained in the study medication (active or placebo).

NOTE: Additional inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Esophagitis, Peptic
• Gastroesophageal Reflux
• Gastroesophageal Reflux Disease

Intervention

Drug:
• IW-3718

• Matching Placebo

• PPI
All participants were taking a standard dose QD PPI (dexlansoprazole, esomeprazole, esomeprazole magnesium, lansoprazole, omeprazole, pantoprazole, pantoprazole sodium sesquihydrate, rabeprazole or rabeprazole sodium) during the study.

Locations

Country	Name	City	State
United States	IW-3718 Investigator	Anaheim	California
United States	IW-3718 Investigator	Annapolis	Maryland
United States	IW-3718 Investigator	Asheville	North Carolina
United States	IW-3718 Investigator	Baltimore	Maryland
United States	IW-3718 Investigator	Bowling Green	Kentucky
United States	IW-3718 Investigator	Bristol	Connecticut
United States	IW-3718 Investigator	Carmichael	California
United States	IW-3718 Investigator	Charleston	South Carolina
United States	IW-3718 Investigator	Chattanooga	Tennessee
United States	IW-3718 Investigator	Chesterfield	Michigan
United States	IW-3718 Investigator	Chevy Chase	Maryland
United States	IW-3718 Investigator	Christiansburg	Virginia
United States	IW-3718 Investigator	Chula Vista	California
United States	IW-3718 Investigator	Cleveland	Ohio
United States	IW-3718 Investigator	Clive	Iowa
United States	IW-3718 Investigator	Columbus	Ohio
United States	IW-3718 Investigator	DeLand	Florida
United States	IW-3718 Investigator	Dothan	Alabama
United States	IW-3718 Investigator	Egg Harbor Township	New Jersey
United States	IW-3718 Investigator	El Paso	Texas
United States	IW-3718 Investigator	Fargo	North Dakota
United States	IW-3718 Investigator	Germantown	Tennessee
United States	IW-3718 Investigator	Great Neck	New York
United States	IW-3718 Investigator	Great Neck	New York
United States	IW-3718 Investigator	Hollywood	Florida
United States	IW-3718 Investigator	Houston	Texas
United States	IW-3718 Investigator	Inverness	Florida
United States	IW-3718 Investigator	Jupiter	Florida
United States	IW-3718 Investigator	Kew Gardens	New York
United States	IW-3718 Investigator	La Mirada	California
United States	IW-3718 Investigator	Las Vegas	Nevada
United States	IW-3718 Investigator	Lauderdale Lakes	Florida
United States	IW-3718 Investigator	Lima	Ohio
United States	IW-3718 Investigator	Lynchburg	Virginia
United States	IW-3718 Investigator	Miami	Florida
United States	IW-3718 Investigator	Miami	Florida
United States	IW-3718 Investigator	Miami Lakes	Florida
United States	IW-3718 Investigator	Mission Hills	California
United States	IW-3718 Investigator	Monroe	Louisiana
United States	IW-3718 Investigator	Nashville	Tennessee
United States	IW-3718 Investigator	New York	New York
United States	IW-3718 Investigator	Newport Beach	California
United States	IW-3718 Investigator	Norman	Oklahoma
United States	IW-3718 Investigator	North Little Rock	Arkansas
United States	IW-3718 Investigator	Oakland	California
United States	IW-3718 Investigator	Oklahoma City	Oklahoma
United States	IW-3718 Investigator	Phoenix	Arizona
United States	IW-3718 Investigator	Pittsburgh	Pennsylvania
United States	IW-3718 Investigator	Port Orange	Florida
United States	IW-3718 Investigator	Raleigh	North Carolina
United States	IW-3718 Investigator	Reno	Nevada
United States	IW-3718 Investigator	Sacramento	California
United States	IW-3718 Investigator	San Antonio	Texas
United States	IW-3718 Investigator	San Antonio	Texas
United States	IW-3718 Investigator	San Diego	California
United States	IW-3718 Investigator	Sandy	Utah
United States	IW-3718 Investigator	South Ogden	Utah
United States	IW-3718 Investigator	Tucson	Arizona
United States	IW-3718 Investigator	Tucson	Arizona
United States	IW-3718 Investigator	Tucson	Arizona
United States	IW-3718 Investigator	Waterbury	Connecticut
United States	IW-3718 Investigator	Wyoming	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
Ironwood Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS)	The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A negative change from Baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8
Secondary	Percent Change From Baseline to Week 4 in WHSS	The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A negative change from Baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4
Secondary	Change From Baseline to Week 8 in WHSS	The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A negative change from Baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8
Secondary	Change From Baseline to Week 4 in WHSS	The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A negative change from Baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4
Secondary	Percentage of Participants Who Are Overall Heartburn Responders	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 >= 30% from baseline in WHSS (see Outcome Measure 1 for description of WHSS). A participant who reported heartburn severity for less than 4 days during a week was not considered a responder for that week.	Week 8
Secondary	Percentage of Participants With a DHSS of No More Than Very Mild (= 1) on Any Day During Week 8	DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A participant who reported heartburn severity for less than 4 days during a week was not considered a responder for that week.	Week 8
Secondary	Percentage of Participants With a DHSS of No More Than Very Mild (= 1) on Any Day During Week 4	DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A participant who reported heartburn severity for less than 4 days during a week was not considered a responder for that week.	Week 4
Secondary	Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (= 1) During Week 8	DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day.	Week 8
Secondary	Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (= 1) During Week 4	DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day.	Week 4
Secondary	Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their heartburn over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from Baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their burning feeling behind the breastbone or in the center of the upper stomach over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their pain behind the breastbone or in the center of the upper stomach over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their difficulty swallowing over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their hoarseness over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their cough over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of their regurgitation (liquid or food moving upwards towards the throat or mouth) over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of an acid or bitter taste in the mouth over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of their cough over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency'	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of their burping over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement.	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Weeks 1, 2, 3, 4, 5, 6, 7, 8
Secondary	Change From Baseline in the Proportion of Heartburn-Free Days During Week 8	A heartburn free day was a day where DHSS = 0. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day.	Week 8
Secondary	Change From Baseline in the Proportion of Heartburn-Free Days During Week 4	A heartburn free day was a day where DHSS = 0. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day.	Week 4