NCT03561090

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

Terminated Phase 3 Results posted Last updated 19 August 2021

What this trial tests

Phase 3 trial testing IW-3718 in Gastroesophageal Reflux Disease (GERD) in 495 participants. Terminated before completion.

Timeline

20 June 2018

Primary endpoint
7 October 2020

3 November 2020

Quick facts

Lead sponsor	Ironwood Pharmaceuticals, Inc.
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	495
Start date	20 June 2018
Primary completion	7 October 2020
Estimated completion	3 November 2020
Sites	99 locations across Canada, United States

Drugs / interventions tested

• IW-3718 — full drug profile →
• placebo
• Standard-dose PPIs QD — full drug profile →

Conditions studied

• Gastroesophageal Reflux Disease (GERD) — all drugs for Gastroesophageal Reflux Disease (GERD) →

Sponsor

Ironwood Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Gastroesophageal Reflux Disease (GERD). Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change From Baseline in WHSS at Week 8 Primary · Baseline, 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.

Group	Value	95% CI
Placebo BID + PPI	-1.774	± 0.082
1500 mg IW-3718 BID + PPI	-1.719	± 0.082

Change From Baseline in Weekly Regurgitation Frequency Score (WRFS) at Week 8 Secondary · Baseline, 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.

Group	Value	95% CI
Placebo BID + PPI	-1.330	± 0.067
1500 mg IW-3718 BID + PPI	-1.294	± 0.068

Percentage of Participants Who Were Overall Heartburn Responders During the 8-Week Treatment Period Secondary · Up 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 breas

Group	Value	95% CI
Placebo BID + PPI	53.1	46.4 – 59.7
1500 mg IW-3718 BID + PPI	47.6	40.9 – 54.3

Proportion of Heartburn-Free Days During the 8-Week Treatment Period Secondary · Up 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

Group	Value	95% CI
Placebo BID + PPI	0.232	± 0.032
1500 mg IW-3718 BID + PPI	0.218	± 0.031

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug through the end of treatment (up to Week 8) plus 7 days.. Reporting threshold: 2%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo BID + PPI

Serious: 0/246 (0%)

Deaths: 0/246

1500 mg IW-3718 BID + PPI

Serious: 3/247 (1%)

Deaths: 0/247

Serious adverse events (3 terms)

Reaction	System	Placebo BID + PPI	1500 mg IW-3718 BID + PPI
Cholecystitis	Hepatobiliary disorders	—	—
COVID-19	Infections and infestations	—	—
Carbon monoxide poisoning	Injury, poisoning and procedural complications	—	—

Other adverse events (8 terms — click to expand)

Reaction	System	Placebo BID + PPI	1500 mg IW-3718 BID + PPI
Diarrhoea	Gastrointestinal disorders	—	—
Flatulence	Gastrointestinal disorders	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Constipation	Gastrointestinal disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Urinary tract infection	Infections and infestations	—	—

Most-reported serious reactions: Cholecystitis, COVID-19, Carbon monoxide poisoning.

Data from ClinicalTrials.gov NCT03561090 adverse events section.

Sponsor's own description

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.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Systematic mapping of registered interventional studies addressing the top 10 research priorities in Barrett's oesophagus and gastro-oesophageal reflux disease.
   Gamakaranage C, Ratcliffe E, Britton J, Butler T, et al · · 2025 · PMID 40527525 · DOI 10.1136/bmjgast-2025-001738