Clinical trial NCT02637557: A Trial of IW-3718 for 8 Weeks in Patients With Symptomatic Gastroesophageal Reflux Disease (GERD)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastroesophageal Reflux Disease
Lead sponsor: Ironwood Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-22
Enrollment: 282
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS)
timeFrame: Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8
Secondary outcomes:
measure: Percent Change From Baseline to Week 4 in WHSS
timeFrame: Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4
measure: Change From Baseline to Week 8 in WHSS
timeFrame: Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8
measure: Change From Baseline to Week 4 in WHSS
timeFrame: Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4
measure: Percentage of Participants Who Are Overall Heartburn Responders
timeFrame: Week 8
measure: Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 8
timeFrame: Week 8
measure: Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 4
timeFrame: Week 4
measure: Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 8
timeFrame: Week 8
measure: Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 4
timeFrame: Week 4
measure: Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity'
timeFrame: 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
measure: Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity'
timeFrame: 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
measure: Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity'
timeFrame: 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
measure: Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity'
timeFrame: 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
measure: Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity'
timeFrame: 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
measure: Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity'
timeFrame: 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
measure: Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency'
timeFrame: 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
measure: Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency'
timeFrame: 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
measure: Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency'
timeFrame: 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
measure: Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency'
timeFrame: 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
measure: Change From Baseline in the Proportion of Heartburn-Free Days During Week 8
timeFrame: Week 8
measure: Change From Baseline in the Proportion of Heartburn-Free Days During Week 4
timeFrame: Week 4
Other outcomes:
Locations:
city: Dothan
country: United States
facility: IW-3718 Investigator
state: Alabama
city: Phoenix
country: United States
facility: IW-3718 Investigator
state: Arizona
city: Tucson
country: United States
facility: IW-3718 Investigator
state: Arizona
city: Tucson
country: United States
facility: IW-3718 Investigator
state: Arizona
city: Tucson
country: United States
facility: IW-3718 Investigator
state: Arizona
city: North Little Rock
country: United States
facility: IW-3718 Investigator
state: Arkansas
city: Anaheim
country: United States
facility: IW-3718 Investigator
state: California
city: Carmichael
country: United States
facility: IW-3718 Investigator
state: California
city: Chula Vista
country: United States
facility: IW-3718 Investigator
state: California
city: La Mirada
country: United States
facility: IW-3718 Investigator
state: California
city: Mission Hills
country: United States
facility: IW-3718 Investigator
state: California
city: Newport Beach
country: United States
facility: IW-3718 Investigator
state: California
city: Oakland
country: United States
facility: IW-3718 Investigator
state: California
city: Sacramento
country: United States
facility: IW-3718 Investigator
state: California
city: San Diego
country: United States
facility: IW-3718 Investigator
state: California
city: Bristol
country: United States
facility: IW-3718 Investigator
state: Connecticut
city: Waterbury
country: United States
facility: IW-3718 Investigator
state: Connecticut
city: DeLand
country: United States
facility: IW-3718 Investigator
state: Florida
city: Hollywood
country: United States
facility: IW-3718 Investigator
state: Florida
city: Inverness
country: United States
facility: IW-3718 Investigator
state: Florida
city: Jupiter
country: United States
facility: IW-3718 Investigator
state: Florida
city: Lauderdale Lakes
country: United States
facility: IW-3718 Investigator
state: Florida
city: Miami Lakes
country: United States
facility: IW-3718 Investigator
state: Florida
city: Miami
country: United States
facility: IW-3718 Investigator
state: Florida
city: Miami
country: United States
facility: IW-3718 Investigator
state: Florida
city: Port Orange
country: United States
facility: IW-3718 Investigator
state: Florida
city: Clive
country: United States
facility: IW-3718 Investigator
state: Iowa
city: Bowling Green
country: United States
facility: IW-3718 Investigator
state: Kentucky
city: Monroe
country: United States
facility: IW-3718 Investigator
state: Louisiana
city: Annapolis
country: United States
facility: IW-3718 Investigator
state: Maryland
city: Baltimore
country: United States
facility: IW-3718 Investigator
state: Maryland
city: Chevy Chase
country: United States
facility: IW-3718 Investigator
state: Maryland
city: Chesterfield
country: United States
facility: IW-3718 Investigator
state: Michigan
city: Wyoming
country: United States
facility: IW-3718 Investigator
state: Michigan
city: Las Vegas
country: United States
facility: IW-3718 Investigator
state: Nevada
city: Reno
country: United States
facility: IW-3718 Investigator
state: Nevada
city: Egg Harbor Township
country: United States
facility: IW-3718 Investigator
state: New Jersey
city: Great Neck
country: United States
facility: IW-3718 Investigator
state: New York
city: Great Neck
country: United States
facility: IW-3718 Investigator
state: New York
city: Kew Gardens
country: United States
facility: IW-3718 Investigator
state: New York
city: New York
country: United States
facility: IW-3718 Investigator
state: New York
city: Asheville
country: United States
facility: IW-3718 Investigator
state: North Carolina
city: Raleigh
country: United States
facility: IW-3718 Investigator
state: North Carolina
city: Fargo
country: United States
facility: IW-3718 Investigator
state: North Dakota
city: Cleveland
country: United States
facility: IW-3718 Investigator
state: Ohio
city: Columbus
country: United States
facility: IW-3718 Investigator
state: Ohio
city: Lima
country: United States
facility: IW-3718 Investigator
state: Ohio
city: Norman
country: United States
facility: IW-3718 Investigator
state: Oklahoma
city: Oklahoma City
country: United States
facility: IW-3718 Investigator
state: Oklahoma
city: Pittsburgh
country: United States
facility: IW-3718 Investigator
state: Pennsylvania
city: Charleston
country: United States
facility: IW-3718 Investigator
state: South Carolina
city: Chattanooga
country: United States
facility: IW-3718 Investigator
state: Tennessee
city: Germantown
country: United States
facility: IW-3718 Investigator
state: Tennessee
city: Nashville
country: United States
facility: IW-3718 Investigator
state: Tennessee
city: El Paso
country: United States
facility: IW-3718 Investigator
state: Texas
city: Houston
country: United States
facility: IW-3718 Investigator
state: Texas
city: San Antonio
country: United States
facility: IW-3718 Investigator
state: Texas
city: San Antonio
country: United States
facility: IW-3718 Investigator
state: Texas
city: Sandy
country: United States
facility: IW-3718 Investigator
state: Utah
city: South Ogden
country: United States
facility: IW-3718 Investigator
state: Utah
city: Christiansburg
country: United States
facility: IW-3718 Investigator
state: Virginia
city: Lynchburg
country: United States
facility: IW-3718 Investigator
state: Virginia
Study officials:
affiliation: Ironwood Pharmaceuticals, Inc.
name: Lara Lane
role: STUDY_DIRECTOR
References:
citation: Vaezi MF, Fass R, Vakil N, Reasner DS, Mittleman RS, Hall M, Shao JZ, Chen Y, Lane L, Gates AM, Currie MG. IW-3718 Reduces Heartburn Severity in Patients With Refractory Gastroesophageal Reflux Disease in a Randomized Trial. Gastroenterology. 2020 Jun;158(8):2093-2103. doi: 10.1053/j.gastro.2020.02.031. Epub 2020 Feb 22.
citation: Andrae DA, Hanlon J, Cala ML, Scippa K, Graham C, Witherspoon B, Shao JZ, Reasner D. Evaluation and Validation of the Modified Reflux Symptom Questionnaire-Electronic Diary in Patients With Persistent Gastroesophageal Reflux Disease. Clin Transl Gastroenterol. 2020 Jan;11(1):e00117. doi: 10.14309/ctg.0000000000000117.