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

Phase 3
Completed
Conditions
Gastroesophageal Reflux Disease (GERD)
Interventions
Drug: placebo
Drug: Standard-dose PPIs QD
Registration Number
NCT03561883
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
COMPLETED
Sex
All
Target Recruitment
609
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboStandard-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.
1500 mg IW-3718 BIDIW-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.
1500 mg IW-3718 BIDStandard-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.
PlaceboplaceboThree 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
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

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.

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

Trial Locations

Locations (99)

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

Digestive Health Specialists of The Southeast

🇺🇸

Dothan, Alabama, United States

Holland Center for Family Health

🇺🇸

Peoria, Arizona, United States

Hope Research Institute LLC

🇺🇸

Peoria, Arizona, United States

Atria Clinical Research

🇺🇸

Little Rock, Arkansas, United States

Preferred Research Partners

🇺🇸

Little Rock, Arkansas, United States

Hope Clinical Research, LLC

🇺🇸

Canoga Park, California, United States

Om Research LLC

🇺🇸

Lancaster, California, United States

Torrance Clinical Research

🇺🇸

Lomita, California, United States

United Gastroenterologists

🇺🇸

Murrieta, California, United States

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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
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