A Trial of IW-3718 for 8 Weeks in Patients With Symptomatic Gastroesophageal Reflux Disease (GERD)

Phase 2

Completed

Conditions: Gastroesophageal Reflux Disease

Interventions: Drug: Matching Placebo
Drug: IW-3718
Drug: PPI

Registration Number: NCT02637557

Lead Sponsor: Ironwood Pharmaceuticals, Inc.

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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 282

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control	Matching Placebo	Matching placebo twice daily
Control	PPI	Matching placebo twice daily
500 mg IW-3718	IW-3718	500 mg IW-3718 twice daily
500 mg IW-3718	PPI	500 mg IW-3718 twice daily
1000 mg IW-3718	IW-3718	1000 mg IW-3718 twice daily
1000 mg IW-3718	PPI	1000 mg IW-3718 twice daily
1500 mg IW-3718	IW-3718	1500 mg IW-3718 twice daily
1500 mg IW-3718	PPI	1500 mg IW-3718 twice daily

Primary Outcome Measures

Name	Time	Method
Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS)	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8	The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A negative change from Baseline indicates improvement.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their hoarseness over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.
Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their cough over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.
Percentage of Participants Who Are Overall Heartburn Responders	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 \>= 30% from baseline in WHSS (see Outcome Measure 1 for description of WHSS). A participant who reported heartburn severity for less than 4 days during a week was not considered a responder for that week.
Percent Change From Baseline to Week 4 in WHSS	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4	The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A negative change from Baseline indicates improvement.
Change From Baseline to Week 8 in WHSS	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8	The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A negative change from Baseline indicates improvement.
Change From Baseline to Week 4 in WHSS	Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4	The WHSS for an analysis week was defined as the average of available DHSS during that week. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A negative change from Baseline indicates improvement.
Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 8	Week 8	DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A participant who reported heartburn severity for less than 4 days during a week was not considered a responder for that week.
Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 4	Week 4	DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day. A participant who reported heartburn severity for less than 4 days during a week was not considered a responder for that week.
Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 8	Week 8	DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day.
Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 4	Week 4	DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day.
Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their heartburn over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from Baseline indicates improvement.
Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their burning feeling behind the breastbone or in the center of the upper stomach over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.
Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their pain behind the breastbone or in the center of the upper stomach over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.
Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the severity of their difficulty swallowing over the past 24 hours on a 6-point scale: 0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe. Daily scores were averaged each week. A negative change from baseline indicates improvement.
Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of their regurgitation (liquid or food moving upwards towards the throat or mouth) over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement.
Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of an acid or bitter taste in the mouth over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement.
Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of their cough over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement.
Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency'	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	The mRESQ-eD questionnaire assesses the severity and frequency of the symptoms participants experience due to reflux disease. Participants were asked to rate the frequency of their burping over the past 24 hours on a 5-point scale: 0=Never, 1= Rarely, 2=Sometimes, 3=Often, 4=Very often. Daily scores were averaged each week. A negative change from baseline indicates improvement.
Change From Baseline in the Proportion of Heartburn-Free Days During Week 8	Week 8	A heartburn free day was a day where DHSS = 0. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day.
Change From Baseline in the Proportion of Heartburn-Free Days During Week 4	Week 4	A heartburn free day was a day where DHSS = 0. DHSS was defined as the maximum on a 6-point scale (0=Did Not Have, 1=Very Mild, 2=Mild, 3=Moderate, 4=Moderately Severe, 5=Severe) of the 3 items measuring heartburn ( "Heartburn," "Burning feeling behind breastbone or in the center of the upper stomach," and "Pain behind breastbone or in the center of the upper stomach,") from a particular day.