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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Gastroesophageal Reflux Disease (GERD)

Intervention / Treatment
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* Drug: IW-3718
* Drug: placebo
* Drug: Standard-dose PPIs QD


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1500 mg IW-3718 BID + PPI<br>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<br>* oral tablet<br>Drug: Standard-dose PPIs QD<br>* background therapy<br>|
| Placebo Comparator: Placebo + PPI<br>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: placebo<br>* oral tablet<br>Drug: Standard-dose PPIs QD<br>* background therapy<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastroesophageal Reflux Disease, GERD, Proton Pump Inhibitors, IW-3718