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

• Sponsor: Ironwood Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Ironwood Pharmaceuticals, Inc.

Study Description

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), standarddose proton pump inhibitors (PPIs).

Condition or disease	Intervention/treatment	Phase
Gastroesophageal Reflux Disease (GERD)	Drug: IW-3718; Drug: placebo	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	660 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
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
Actual Study Start Date :	September 6, 2018
Estimated Primary Completion Date :	January 2020
Estimated Study Completion Date :	January 2020

Arms and Interventions

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.	Drug: IW-3718; oral tablet
Placebo Comparator: Placebo; Three placebo tablets administered BID immediately after the morning and evening meals.	Drug: placebo; oral tablet

Outcome Measures

Primary Outcome Measures :

1. Proportion of Overall Heartburn Responders [ Time Frame: Week 8 ]

Secondary Outcome Measures :

1. Proportion of Overall Heartburn Responders Among Participants With a Baseline Weekly Heartburn Severity Score (WHSS) ≥ 3 [ Time Frame: Week 8 ]
2. Percent Change From Baseline to Week 8 in WHSS [ Time Frame: Baseline, Week 8 ]
3. Percent Change From Baseline to Week 8 in Weekly Regurgitation Frequency Score (WRFS) [ Time Frame: Baseline, Week 8 ]
4. Proportion of Heartburn-Free (Daily Heartburn Severity Score [DHSS]=0) Days During the 8-Week Treatment Period [ Time Frame: up to Week 8 ]
5. Proportion of Overall Regurgitation Responders [ Time Frame: up to Week 8 ]
6. Proportion of Days When Heartburn Did Not Occur (DHSS=0) or Was Very Mild (DHSS=1) During the 8-Week Treatment Period [ Time Frame: Week 8 ]
7. Proportion of Days When Regurgitation Did Not Occur (Daily Regurgitation Frequency Scores [DRFS]=0) or Rarely Occurred (DRFS=1) During the 8-Week Treatment Period [ Time Frame: Week 8 ]
8. Proportion of Regurgitation-Free (DRFS=0) Days During the 8-Week Treatment Period [ Time Frame: Week 8 ]
9. Change From Baseline to Week 8 in Each Modified Reflux Symptom Questionnaire Electronic Diary (mRESQ) Item [ Time Frame: Baseline, Week 8 ]
10. Proportion of Nights With Difficulty Falling Asleep Due to GERD During the 8-Week Treatment Period [ Time Frame: Week 8 ]
11. Proportion of Days With Nighttime Awakening Due to GERD During the 8-Week Treatment Period [ Time Frame: Week 8 ]
12. Number of Degree of Relief (of Heartburn/Regurgitation/Overall GERD Symptoms) Responders [ Time Frame: up to Week 8 ]
13. Change From Baseline to Week 8 in Heartburn/Regurgitation/Overall GERD Symptoms Bothersomeness [ Time Frame: Baseline, Week 8 ]
14. Proportion of Days With Rescue Medication Use During the 8-Week Treatment Period [ Time Frame: up to Week 8 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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 proton pump inhibitor (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, 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.

Contacts and Locations

Contacts

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Contact: Ironwood Study Team		IW3718@ironwoodpharma.com

  Show 88 Study Locations

Sponsors and Collaborators

Ironwood Pharmaceuticals, Inc.

Investigators

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Study Chair:	Zurab Machaidze, MD	Ironwood Pharmaceuticals, Inc.

More Information

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Responsible Party:	Ironwood Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT03561883 History of Changes
Other Study ID Numbers:	C3718-302
First Posted:	June 19, 2018
Last Update Posted:	January 10, 2019
Last Verified:	January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:		Yes
Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Ironwood Pharmaceuticals, Inc.:

Gastroesophageal Reflux Disease; GERD; Proton Pump Inhibitor; IW-3718

Additional relevant MeSH terms:

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Gastroesophageal Reflux; Esophagitis, Peptic; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Esophagitis	Gastroenteritis; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases; Proton Pump Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action