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CompletedNCT02637557Updated Oct 15, 2019Results posted

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

A Phase 2 interventional study of IW-3718 and Matching Placebo in Gastroesophageal Reflux Disease, sponsored by Ironwood Pharmaceuticals, Inc.. Completed at 62 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-10-15.

Sponsored by Ironwood Pharmaceuticals, Inc. · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
282
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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).

02

Conditions studied

  • Gastroesophageal Reflux Disease
03

In context

Gastroesophageal Reflux

1,066 studies on the registry are indexed under Gastroesophageal Reflux; 188 are open to participants now.

This study's enrollment of 282 is above the median of 72 across 711 interventional studies indexed under Gastroesophageal Reflux.

Browse Gastroesophageal Reflux studies →

Lead sponsor

Ironwood Pharmaceuticals, Inc. is the lead sponsor of 24 studies on the registry; none are open to participants now.

Of its 9 completed or terminated interventional studies of FDA-regulated products, 8 (89%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
282 participants (actual)

Study arms

  • Placebo comparator
    Control

    Matching placebo twice daily

    Drug: Matching Placebo · Drug: PPI

  • Experimental
    500 mg IW-3718

    500 mg IW-3718 twice daily

    Drug: IW-3718 · Drug: PPI

  • Experimental
    1000 mg IW-3718

    1000 mg IW-3718 twice daily

    Drug: IW-3718 · Drug: PPI

  • Experimental
    1500 mg IW-3718

    1500 mg IW-3718 twice daily

    Drug: IW-3718 · Drug: PPI

Interventions

  • DrugIW-3718
  • DrugMatching Placebo
  • DrugPPI

    All participants were taking a standard dose QD PPI (dexlansoprazole, esomeprazole, esomeprazole magnesium, lansoprazole, omeprazole, pantoprazole, pantoprazole sodium sesquihydrate, rabeprazole or rabeprazole sodium) during the study.

06

What researchers measure

Primary outcomes

  1. Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS)

    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.

    Time frame: Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8

Secondary outcomes

  1. Percent Change From Baseline to Week 4 in WHSS

    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.

    Time frame: Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4

  2. Change From Baseline to Week 8 in WHSS

    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.

    Time frame: Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8

  3. Change From Baseline to Week 4 in WHSS

    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.

    Time frame: Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4

  4. Percentage of Participants Who Are Overall Heartburn Responders

    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.

    Time frame: Week 8

  5. Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During 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.

    Time frame: Week 8

  6. Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During 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.

    Time frame: Week 4

  7. Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During 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.

    Time frame: Week 8

  8. Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During 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.

    Time frame: Week 4

  9. Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity'

    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.

    Time frame: 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

  10. Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity'

    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.

    Time frame: 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

  11. Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity'

    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.

    Time frame: 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

  12. Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity'

    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.

    Time frame: 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

  13. Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity'

    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.

    Time frame: 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

  14. Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity'

    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.

    Time frame: 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

  15. Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency'

    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.

    Time frame: 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

  16. Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency'

    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.

    Time frame: 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

  17. Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency'

    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.

    Time frame: 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

  18. Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency'

    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.

    Time frame: 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

  19. Change From Baseline in the Proportion of Heartburn-Free Days During 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.

    Time frame: Week 8

  20. Change From Baseline in the Proportion of Heartburn-Free Days During 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.

    Time frame: Week 4

07

Results

Posted Oct 15, 2019

Participant flow

Participant flow — Overall Study
MilestonePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Started71717169
Completed63666262
Not completed8597
Withdrew: Adverse event3133
Withdrew: Lost to follow-up1101
Withdrew: Physician decision1000
Withdrew: Protocol violation2021
Withdrew: Withdrawal by subject1342

Outcome measures

PrimaryPercent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS)

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.

Time frame:
Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8
Reported as:
Least squares mean · percentage change in score
Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS)
percentage change in scorePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Percent Change From Baseline to Week 8 in Weekly Heartburn Severity Score (WHSS)-46.026 ± 4.078-48.978 ± 4.019-55.063 ± 4.024-57.969 ± 4.108
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6065 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -2.952 · 95% CI -14.222 to 8.318
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1160 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -9.036 · 95% CI -20.318 to 2.245
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0400 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -11.943 · 95% CI -23.334 to -0.551
  • Placebo BID vs 500 mg IW-3718 BID vs 1000 mg IW-3718 BID vs 1500 mg IW-3718 BID · trend test · p = 0.0225 (Dose trend test performed using linear contrast statement.)
SecondaryPercent Change From Baseline to Week 4 in WHSS

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.

Time frame:
Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4
Reported as:
Least squares mean · percentage change in score
Percent Change From Baseline to Week 4 in WHSS
percentage change in scorePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Percent Change From Baseline to Week 4 in WHSS-38.883 ± 3.733-42.594 ± 3.679-41.622 ± 3.683-47.486 ± 3.761
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4795 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -3.711 · 95% CI -14.028 to 6.606
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.6020 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -2.739 · 95% CI -13.066 to 7.588
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.1055 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -8.602 · 95% CI -19.030 to 1.826
  • Placebo BID vs 500 mg IW-3718 BID vs 1000 mg IW-3718 BID vs 1500 mg IW-3718 BID · trend test · p = 0.1387 (Dose trend test performed using linear contrast statement.)
SecondaryChange From Baseline to Week 8 in WHSS

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.

Time frame:
Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 8
Reported as:
Least squares mean · score on a scale
Change From Baseline to Week 8 in WHSS
score on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Change From Baseline to Week 8 in WHSS-1.459 ± 0.129-1.517 ± 0.127-1.713 ± 0.127-1.876 ± 0.130
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7488 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.058 · 95% CI -0.415 to 0.299
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1627 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.254 · 95% CI -0.611 to 0.103
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0237 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.417 · 95% CI -0.777 to -0.056
  • Placebo BID vs 500 mg IW-3718 BID vs 1000 mg IW-3718 BID vs 1500 mg IW-3718 BID · trend test · p = 0.0130 (Dose trend test performed using linear contrast statement.)
SecondaryChange From Baseline to Week 4 in WHSS

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.

Time frame:
Baseline (derived from the eDiary daily data collected from 7 days before randomization up to the time of randomization), Week 4
Reported as:
Least squares mean · score on a scale
Change From Baseline to Week 4 in WHSS
score on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Change From Baseline to Week 4 in WHSS-1.261 ± 0.115-1.313 ± 0.113-1.308 ± 0.113-1.517 ± 0.115
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7470 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.052 · 95% CI -0.369 to 0.265
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.7699 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.047 · 95% CI -0.364 to 0.270
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.1157 (P-value based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.257 · 95% CI -0.577 to 0.064
  • Placebo BID vs 500 mg IW-3718 BID vs 1000 mg IW-3718 BID vs 1500 mg IW-3718 BID · trend test · p = 0.1374 (Dose trend test performed using linear contrast statement.)
SecondaryPercentage of Participants Who Are Overall Heartburn Responders

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.

Time frame:
Week 8
Reported as:
Number · percentage of participants
Percentage of Participants Who Are Overall Heartburn Responders
percentage of participantsPlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Percentage of Participants Who Are Overall Heartburn Responders54.3 (41.9 to 66.3)52.1 (39.9 to 64.1)62.0 (49.7 to 73.2)66.2 (53.7 to 77.2)
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · Cochran-Mantel-Haenszel · p = 0.7903 (Odds ratio, 95% confidence interval (CI) for the odds ratio and p-value vs. placebo are obtained from the Cochran-Mantel-Haenszel (CMH) tests controlling for esophagitis status.) · Odds ratio (or): 0.91 · 95% CI 0.47 to 1.77
  • Placebo BID vs 1000 mg IW-3718 BID · Cochran-Mantel-Haenszel · p = 0.3518 (Odds ratio, 95% CI for the odds ratio and p-value vs. placebo are obtained from the CMH tests controlling for esophagitis status.) · Odds ratio (or): 1.38 · 95% CI 0.70 to 2.71
  • Placebo BID vs 1500 mg IW-3718 BID · Cochran-Mantel-Haenszel · p = 0.1544 (Odds ratio, 95% CI for the odds ratio and p-value vs. placebo are obtained from the CMH tests controlling for esophagitis status.) · Odds ratio (or): 1.64 · 95% CI 0.83 to 3.26
SecondaryPercentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During 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.

Time frame:
Week 8
Reported as:
Number · percentage of participants
Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 8
percentage of participantsPlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 828.6 (18.4 to 40.6)18.3 (10.1 to 29.3)29.6 (19.3 to 41.6)38.2 (26.7 to 50.8)
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · Cochran-Mantel-Haenszel · p = 0.1489 (Odds ratio, 95% CI for the odds ratio and p-value vs. placebo are obtained from the CMH tests controlling for esophagitis status.) · Odds ratio (or): 0.56 · 95% CI 0.25 to 1.23
  • Placebo BID vs 1000 mg IW-3718 BID · Cochran-Mantel-Haenszel · p = 0.8891 (Odds ratio, 95% CI for the odds ratio and p-value vs. placebo are obtained from the CMH tests controlling for esophagitis status.) · Odds ratio (or): 1.05 · 95% CI 0.51 to 2.19
  • Placebo BID vs 1500 mg IW-3718 BID · Cochran-Mantel-Haenszel · p = 0.2237 (Odds ratio, 95% CI for the odds ratio and p-value vs. placebo are obtained from the CMH tests controlling for esophagitis status.) · Odds ratio (or): 1.56 · 95% CI 0.76 to 3.20
SecondaryPercentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During 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.

Time frame:
Week 4
Reported as:
Number · percentage of participants
Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 4
percentage of participantsPlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Percentage of Participants With a DHSS of No More Than Very Mild (≤ 1) on Any Day During Week 412.9 (6.1 to 23.0)15.5 (8.0 to 26.0)22.5 (13.5 to 34.0)22.1 (12.9 to 33.8)
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · Cochran-Mantel-Haenszel · p = 0.6566 (Odds ratio, 95% CI (Confidence Interval) for the Odds Ratio and p-value vs. placebo are obtained from the CMH tests controlling for esophagitis status.) · Odds ratio (or): 1.24 · 95% CI 0.48 to 3.18
  • Placebo BID vs 1000 mg IW-3718 BID · Cochran-Mantel-Haenszel · p = 0.1280 (Odds ratio, 95% CI (Confidence Interval) for the Odds Ratio and p-value vs. placebo are obtained from the CMH tests controlling for esophagitis status.) · Odds ratio (or): 2.01 · 95% CI 0.81 to 4.98
  • Placebo BID vs 1500 mg IW-3718 BID · Cochran-Mantel-Haenszel · p = 0.1463 (Odds ratio, 95% CI (Confidence Interval) for the Odds Ratio and p-value vs. placebo are obtained from the CMH tests controlling for esophagitis status.) · Odds ratio (or): 1.97 · 95% CI 0.79 to 4.91
SecondaryChange From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During 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.

Time frame:
Week 8
Reported as:
Least squares mean · days
Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 8
daysPlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 82.998 ± 0.3582.700 ± 0.3473.250 ± 0.3553.510 ± 0.359
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5504 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.298 · 95% CI -1.279 to 0.683
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.6177 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.252 · 95% CI -0.741 to 1.244
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.3138 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.513 · 95% CI -0.488 to 1.513
SecondaryChange From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During 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.

Time frame:
Week 4
Reported as:
Least squares mean · days
Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 4
daysPlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Change From Baseline in the Number of Days Where DHSS Was No More Than Very Mild (≤ 1) During Week 42.275 ± 0.3362.294 ± 0.3222.694 ± 0.3292.736 ± 0.327
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.9675 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.019 · 95% CI -0.897 to 0.935
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.3741 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.419 · 95% CI -0.507 to 1.345
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.3275 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.461 · 95% CI -0.464 to 1.385
SecondaryChange From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the Weekly Average of Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.655 ± 0.090-0.632 ± 0.089-0.531 ± 0.089-0.673 ± 0.091
Week 2-0.994 ± 0.102-0.974 ± 0.101-0.977 ± 0.101-1.102 ± 0.103
Week 3-1.092 ± 0.109-1.141 ± 0.107-1.153 ± 0.107-1.350 ± 0.109
Week 4-1.263 ± 0.112-1.281 ± 0.110-1.259 ± 0.110-1.498 ± 0.112
Week 5-1.284 ± 0.120-1.301 ± 0.119-1.339 ± 0.119-1.677 ± 0.121
Week 6-1.396 ± 0.121-1.343 ± 0.119-1.467 ± 0.119-1.744 ± 0.122
Week 7-1.392 ± 0.127-1.350 ± 0.125-1.436 ± 0.125-1.693 ± 0.128
Week 8-1.404 ± 0.127-1.482 ± 0.126-1.666 ± 0.126-1.807 ± 0.128
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8560 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.023 · 95% CI -0.226 to 0.272
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.3301 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.124 · 95% CI -0.126 to 0.373
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.8845 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.019 · 95% CI -0.270 to 0.233
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8879 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.020 · 95% CI -0.262 to 0.303
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.9072 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.017 · 95% CI -0.266 to 0.299
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.4573 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.108 · 95% CI -0.393 to 0.177
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7476 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.049 · 95% CI -0.350 to 0.251
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.6873 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.062 · 95% CI -0.362 to 0.239
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0952 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.258 · 95% CI -0.562 to 0.045
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.9111 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.018 · 95% CI -0.326 to 0.291
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.9772 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.004 · 95% CI -0.304 to 0.313
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.1390 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.235 · 95% CI -0.546 to 0.077
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.9215 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.017 · 95% CI -0.349 to 0.316
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.7453 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.055 · 95% CI -0.388 to 0.278
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0220 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.393 · 95% CI -0.729 to -0.057
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7561 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.053 · 95% CI -0.282 to 0.387
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.6758 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.071 · 95% CI -0.406 to 0.263
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0434 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.348 · 95% CI -0.686 to -0.010
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8123 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.042 · 95% CI -0.308 to 0.392
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.8038 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.044 · 95% CI -0.394 to 0.306
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0954 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.300 · 95% CI -0.654 to 0.053
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6649 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.078 · 95% CI -0.430 to 0.275
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1448 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.262 · 95% CI -0.614 to 0.091
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0264 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.403 · 95% CI -0.759 to -0.048
SecondaryChange From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the Weekly Average of mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.638 ± 0.089-0.536 ± 0.087-0.492 ± 0.088-0.675 ± 0.089
Week 2-0.998 ± 0.103-0.918 ± 0.101-0.970 ± 0.102-1.116 ± 0.104
Week 3-1.040 ± 0.108-1.074 ± 0.106-1.112 ± 0.107-1.385 ± 0.109
Week 4-1.199 ± 0.113-1.246 ± 0.112-1.316 ± 0.112-1.497 ± 0.114
Week 5-1.226 ± 0.120-1.287 ± 0.118-1.323 ± 0.118-1.648 ± 0.121
Week 6-1.357 ± 0.119-1.297 ± 0.117-1.450 ± 0.117-1.733 ± 0.120
Week 7-1.310 ± 0.124-1.359 ± 0.122-1.424 ± 0.122-1.676 ± 0.125
Week 8-1.329 ± 0.122-1.422 ± 0.120-1.627 ± 0.121-1.781 ± 0.123
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4137 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.102 · 95% CI -0.143 to 0.347
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.2395 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.147 · 95% CI -0.098 to 0.392
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.7729 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.036 · 95% CI -0.284 to 0.212
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5824 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.079 · 95% CI -0.205 to 0.363
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.8466 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.028 · 95% CI -0.256 to 0.312
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.4192 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.118 · 95% CI -0.405 to 0.169
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8192 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.035 · 95% CI -0.333 to 0.264
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.6320 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.073 · 95% CI -0.372 to 0.226
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0254 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.345 · 95% CI -0.647 to -0.043
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7689 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.047 · 95% CI -0.360 to 0.266
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4631 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.117 · 95% CI -0.430 to 0.196
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0651 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.298 · 95% CI -0.615 to 0.019
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7197 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.060 · 95% CI -0.392 to 0.271
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5649 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.097 · 95% CI -0.428 to 0.234
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0138 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.422 · 95% CI -0.757 to -0.087
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7202 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.060 · 95% CI -0.269 to 0.388
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5784 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.093 · 95% CI -0.421 to 0.236
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0266 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.376 · 95% CI -0.708 to -0.044
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7770 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.049 · 95% CI -0.391 to 0.293
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5121 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.114 · 95% CI -0.456 to 0.228
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0384 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.366 · 95% CI -0.711 to -0.020
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5876 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.093 · 95% CI -0.431 to 0.245
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0842 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.298 · 95% CI -0.636 to 0.040
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0098 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.452 · 95% CI -0.793 to -0.110
SecondaryChange From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.602 ± 0.089-0.548 ± 0.088-0.454 ± 0.089-0.626 ± 0.090
Week 2-0.921 ± 0.103-0.869 ± 0.101-0.934 ± 0.102-1.083 ± 0.103
Week 3-1.002 ± 0.110-1.008 ± 0.108-1.126 ± 0.109-1.313 ± 0.111
Week 4-1.185 ± 0.113-1.210 ± 0.111-1.244 ± 0.112-1.439 ± 0.114
Week 5-1.279 ± 0.119-1.230 ± 0.117-1.299 ± 0.118-1.578 ± 0.120
Week 6-1.343 ± 0.118-1.257 ± 0.117-1.367 ± 0.117-1.665 ± 0.119
Week 7-1.252 ± 0.122-1.303 ± 0.121-1.302 ± 0.121-1.638 ± 0.124
Week 8-1.289 ± 0.121-1.333 ± 0.119-1.525 ± 0.119-1.674 ± 0.122
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6663 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.054 · 95% CI -0.193 to 0.301
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.2400 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.148 · 95% CI -0.100 to 0.396
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.8560 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.023 · 95% CI -0.273 to 0.227
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7209 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.051 · 95% CI -0.232 to 0.335
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.9283 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.013 · 95% CI -0.297 to 0.271
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.2659 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.162 · 95% CI -0.449 to 0.124
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.9680 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.006 · 95% CI -0.310 to 0.298
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4213 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.125 · 95% CI -0.429 to 0.180
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0471 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.311 · 95% CI -0.618 to -0.004
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8769 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.025 · 95% CI -0.337 to 0.288
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.7109 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.059 · 95% CI -0.372 to 0.254
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.1146 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.254 · 95% CI -0.570 to 0.062
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7736 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.048 · 95% CI -0.281 to 0.378
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.9059 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.020 · 95% CI -0.350 to 0.310
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0779 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.299 · 95% CI -0.633 to 0.034
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6068 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.086 · 95% CI -0.241 to 0.412
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.8838 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.024 · 95% CI -0.352 to 0.303
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0556 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.323 · 95% CI -0.653 to 0.008
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7673 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.051 · 95% CI -0.389 to 0.287
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.7709 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.050 · 95% CI -0.389 to 0.289
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0273 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.386 · 95% CI -0.728 to -0.043
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7950 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.044 · 95% CI -0.378 to 0.289
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1656 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.236 · 95% CI -0.570 to 0.098
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0254 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.385 · 95% CI -0.722 to -0.048
SecondaryChange From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the mRESQ-eD Item 'Difficulty Swallowing Severity'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.498 ± 0.075-0.405 ± 0.074-0.309 ± 0.074-0.519 ± 0.076
Week 2-0.618 ± 0.088-0.566 ± 0.086-0.611 ± 0.087-0.714 ± 0.088
Week 3-0.671 ± 0.094-0.675 ± 0.092-0.817 ± 0.092-1.022 ± 0.094
Week 4-0.737 ± 0.098-0.763 ± 0.096-0.810 ± 0.096-1.061 ± 0.098
Week 5-0.824 ± 0.098-0.850 ± 0.096-0.846 ± 0.096-1.156 ± 0.098
Week 6-0.883 ± 0.102-0.805 ± 0.100-0.961 ± 0.100-1.174 ± 0.102
Week 7-0.849 ± 0.107-0.756 ± 0.105-0.906 ± 0.106-1.166 ± 0.108
Week 8-0.864 ± 0.107-0.822 ± 0.105-0.989 ± 0.105-1.197 ± 0.107
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.3788 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.093 · 95% CI -0.114 to 0.300
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0761 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.189 · 95% CI -0.020 to 0.397
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.8415 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.021 · 95% CI -0.232 to 0.189
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6719 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.052 · 95% CI -0.190 to 0.294
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.9549 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.007 · 95% CI -0.237 to 0.251
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.4408 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.096 · 95% CI -0.342 to 0.149
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.9736 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.004 · 95% CI -0.262 to 0.253
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.2703 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.146 · 95% CI -0.405 to 0.114
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0087 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.351 · 95% CI -0.612 to -0.089
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8480 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.026 · 95% CI -0.295 to 0.243
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5966 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.073 · 95% CI -0.344 to 0.198
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0203 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.324 · 95% CI -0.596 to -0.051
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8540 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.025 · 95% CI -0.294 to 0.244
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.8757 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.022 · 95% CI -0.293 to 0.250
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0174 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.332 · 95% CI -0.605 to -0.059
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5831 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.078 · 95% CI -0.202 to 0.358
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5859 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.078 · 95% CI -0.360 to 0.204
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0447 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.291 · 95% CI -0.575 to -0.007
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5365 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.093 · 95% CI -0.203 to 0.388
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.7067 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.057 · 95% CI -0.355 to 0.241
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0386 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.317 · 95% CI -0.616 to -0.017
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7804 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.042 · 95% CI -0.253 to 0.336
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4064 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.125 · 95% CI -0.422 to 0.171
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0289 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.333 · 95% CI -0.632 to -0.035
SecondaryChange From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the mRESQ-eD Item 'Hoarseness Severity'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.329 ± 0.074-0.292 ± 0.073-0.400 ± 0.073-0.406 ± 0.074
Week 2-0.483 ± 0.090-0.416 ± 0.089-0.605 ± 0.089-0.544 ± 0.091
Week 3-0.526 ± 0.095-0.574 ± 0.094-0.796 ± 0.094-0.778 ± 0.096
Week 4-0.505 ± 0.102-0.631 ± 0.101-0.842 ± 0.101-0.833 ± 0.103
Week 5-0.588 ± 0.107-0.684 ± 0.106-0.870 ± 0.106-0.842 ± 0.108
Week 6-0.617 ± 0.110-0.677 ± 0.108-0.990 ± 0.108-0.962 ± 0.110
Week 7-0.570 ± 0.111-0.626 ± 0.109-0.860 ± 0.109-1.054 ± 0.111
Week 8-0.604 ± 0.108-0.683 ± 0.107-0.954 ± 0.107-1.086 ± 0.109
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7207 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.037 · 95% CI -0.167 to 0.241
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4946 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.071 · 95% CI -0.275 to 0.133
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.4596 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.077 · 95% CI -0.283 to 0.129
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5987 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.067 · 95% CI -0.182 to 0.315
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.3348 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.122 · 95% CI -0.372 to 0.127
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.6288 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.062 · 95% CI -0.313 to 0.190
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7193 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.048 · 95% CI -0.312 to 0.216
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0452 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.270 · 95% CI -0.534 to -0.006
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0635 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.252 · 95% CI -0.519 to 0.014
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.3800 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.126 · 95% CI -0.409 to 0.156
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0200 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.336 · 95% CI -0.620 to -0.053
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0244 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.328 · 95% CI -0.614 to -0.043
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5232 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.096 · 95% CI -0.392 to 0.200
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0623 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.282 · 95% CI -0.579 to 0.015
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0951 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.255 · 95% CI -0.554 to 0.045
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6985 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.060 · 95% CI -0.363 to 0.243
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0163 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.373 · 95% CI -0.677 to -0.069
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0273 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.345 · 95% CI -0.652 to -0.039
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7187 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.056 · 95% CI -0.362 to 0.250
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0640 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.290 · 95% CI -0.596 to 0.017
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0023 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.484 · 95% CI -0.793 to -0.175
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6033 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.079 · 95% CI -0.378 to 0.220
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0222 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.350 · 95% CI -0.650 to -0.050
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0019 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.482 · 95% CI -0.785 to -0.180
SecondaryChange From Baseline Over Time in the mRESQ-eD Item 'Cough Severity'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the mRESQ-eD Item 'Cough Severity'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.426 ± 0.078-0.283 ± 0.076-0.353 ± 0.076-0.389 ± 0.078
Week 2-0.574 ± 0.095-0.501 ± 0.093-0.608 ± 0.093-0.589 ± 0.095
Week 3-0.534 ± 0.092-0.614 ± 0.090-0.745 ± 0.090-0.890 ± 0.092
Week 4-0.530 ± 0.099-0.657 ± 0.097-0.878 ± 0.097-0.914 ± 0.099
Week 5-0.616 ± 0.106-0.692 ± 0.104-0.840 ± 0.104-0.972 ± 0.107
Week 6-0.634 ± 0.107-0.671 ± 0.105-0.953 ± 0.105-1.026 ± 0.107
Week 7-0.594 ± 0.112-0.688 ± 0.110-0.971 ± 0.110-1.063 ± 0.112
Week 8-0.613 ± 0.107-0.706 ± 0.105-0.949 ± 0.105-1.158 ± 0.107
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.1922 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.143 · 95% CI -0.072 to 0.357
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5091 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.072 · 95% CI -0.143 to 0.288
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.7394 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.037 · 95% CI -0.181 to 0.254
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5845 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.073 · 95% CI -0.189 to 0.334
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.7959 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.034 · 95% CI -0.296 to 0.228
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.9086 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.015 · 95% CI -0.280 to 0.249
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5334 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.080 · 95% CI -0.333 to 0.173
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1020 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.212 · 95% CI -0.466 to 0.042
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0066 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.357 · 95% CI -0.613 to -0.100
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.3586 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.127 · 95% CI -0.399 to 0.145
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0128 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.348 · 95% CI -0.621 to -0.075
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0064 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.384 · 95% CI -0.660 to -0.109
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6124 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.076 · 95% CI -0.369 to 0.218
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1365 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.223 · 95% CI -0.518 to 0.071
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0193 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.355 · 95% CI -0.652 to -0.058
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8046 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.037 · 95% CI -0.333 to 0.258
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0350 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.319 · 95% CI -0.616 to -0.023
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0105 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.392 · 95% CI -0.691 to -0.093
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5482 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.094 · 95% CI -0.403 to 0.214
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0170 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.377 · 95% CI -0.687 to -0.068
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0034 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.469 · 95% CI -0.781 to -0.157
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5346 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.093 · 95% CI -0.388 to 0.202
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0262 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.336 · 95% CI -0.632 to -0.040
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0004 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.545 · 95% CI -0.843 to -0.246
SecondaryChange From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the mRESQ-eD Item 'Regurgitation Frequency'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.483 ± 0.067-0.385 ± 0.066-0.340 ± 0.066-0.511 ± 0.068
Week 2-0.647 ± 0.082-0.637 ± 0.081-0.597 ± 0.081-0.774 ± 0.083
Week 3-0.581 ± 0.084-0.784 ± 0.083-0.791 ± 0.083-0.879 ± 0.085
Week 4-0.769 ± 0.089-0.855 ± 0.088-0.838 ± 0.087-0.984 ± 0.089
Week 5-0.758 ± 0.087-0.869 ± 0.086-0.866 ± 0.085-1.028 ± 0.087
Week 6-0.834 ± 0.090-0.936 ± 0.089-0.939 ± 0.089-1.093 ± 0.090
Week 7-0.796 ± 0.090-0.899 ± 0.089-0.867 ± 0.089-1.081 ± 0.091
Week 8-0.811 ± 0.092-0.951 ± 0.091-1.029 ± 0.091-1.191 ± 0.093
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.3007 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.098 · 95% CI -0.088 to 0.284
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1295 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.143 · 95% CI -0.042 to 0.328
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.7671 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.028 · 95% CI -0.216 to 0.159
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.9308 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.010 · 95% CI -0.217 to 0.238
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.6595 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.051 · 95% CI -0.176 to 0.277
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.2771 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.127 · 95% CI -0.356 to 0.102
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.0887 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.203 · 95% CI -0.436 to 0.031
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0758 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.210 · 95% CI -0.443 to 0.022
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0132 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.298 · 95% CI -0.534 to -0.063
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4903 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.086 · 95% CI -0.332 to 0.160
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5824 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.068 · 95% CI -0.313 to 0.176
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0885 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.215 · 95% CI -0.463 to 0.033
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.3652 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.111 · 95% CI -0.352 to 0.130
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.3739 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.108 · 95% CI -0.348 to 0.131
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0294 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.270 · 95% CI -0.512 to -0.027
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4236 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.102 · 95% CI -0.351 to 0.148
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4071 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.105 · 95% CI -0.353 to 0.144
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0434 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.259 · 95% CI -0.510 to -0.008
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4172 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.103 · 95% CI -0.354 to 0.147
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5759 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.071 · 95% CI -0.321 to 0.179
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0271 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.285 · 95% CI -0.538 to -0.033
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.2804 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.140 · 95% CI -0.395 to 0.115
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.0913 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.218 · 95% CI -0.472 to 0.035
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0039 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.380 · 95% CI -0.637 to -0.123
SecondaryChange From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the mRESQ-eD Item 'Acid or Bitter Taste Frequency'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.502 ± 0.069-0.374 ± 0.068-0.401 ± 0.068-0.530 ± 0.070
Week 2-0.738 ± 0.084-0.640 ± 0.082-0.676 ± 0.082-0.784 ± 0.084
Week 3-0.691 ± 0.082-0.806 ± 0.081-0.842 ± 0.081-0.874 ± 0.083
Week 4-0.797 ± 0.090-0.847 ± 0.088-0.893 ± 0.088-0.952 ± 0.090
Week 5-0.868 ± 0.089-0.920 ± 0.087-0.929 ± 0.087-1.024 ± 0.089
Week 6-0.870 ± 0.092-0.966 ± 0.091-1.009 ± 0.091-1.098 ± 0.093
Week 7-0.895 ± 0.094-0.912 ± 0.092-0.947 ± 0.092-1.053 ± 0.094
Week 8-0.896 ± 0.094-0.938 ± 0.093-1.072 ± 0.093-1.163 ± 0.095
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.1902 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.128 · 95% CI -0.064 to 0.319
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.3021 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.100 · 95% CI -0.091 to 0.292
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.7750 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.028 · 95% CI -0.221 to 0.165
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4022 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.099 · 95% CI -0.133 to 0.330
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5971 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.062 · 95% CI -0.169 to 0.293
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.7024 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.045 · 95% CI -0.279 to 0.188
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.3173 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.115 · 95% CI -0.342 to 0.111
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1906 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.151 · 95% CI -0.378 to 0.076
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.1177 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.183 · 95% CI -0.412 to 0.046
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6936 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.050 · 95% CI -0.297 to 0.198
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4466 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.096 · 95% CI -0.343 to 0.152
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.2225 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.155 · 95% CI -0.405 to 0.095
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6764 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.052 · 95% CI -0.297 to 0.193
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.6243 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.061 · 95% CI -0.306 to 0.184
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.2151 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.156 · 95% CI -0.403 to 0.091
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4611 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.096 · 95% CI -0.351 to 0.160
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.2849 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.139 · 95% CI -0.394 to 0.116
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0833 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.228 · 95% CI -0.485 to 0.030
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8955 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.017 · 95% CI -0.277 to 0.242
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.6916 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.052 · 95% CI -0.312 to 0.207
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.2345 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.159 · 95% CI -0.421 to 0.103
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7466 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.043 · 95% CI -0.304 to 0.218
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1843 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.176 · 95% CI -0.437 to 0.084
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0471 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.267 · 95% CI -0.531 to -0.003
SecondaryChange From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the mRESQ-eD Item 'Coughing Frequency'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.374 ± 0.064-0.286 ± 0.063-0.290 ± 0.063-0.352 ± 0.064
Week 2-0.572 ± 0.081-0.469 ± 0.079-0.484 ± 0.079-0.571 ± 0.081
Week 3-0.477 ± 0.083-0.605 ± 0.081-0.594 ± 0.081-0.729 ± 0.083
Week 4-0.497 ± 0.089-0.667 ± 0.087-0.685 ± 0.087-0.793 ± 0.089
Week 5-0.506 ± 0.095-0.659 ± 0.093-0.648 ± 0.093-0.812 ± 0.095
Week 6-0.594 ± 0.092-0.653 ± 0.090-0.700 ± 0.090-0.872 ± 0.092
Week 7-0.561 ± 0.097-0.656 ± 0.095-0.713 ± 0.095-0.872 ± 0.097
Week 8-0.554 ± 0.095-0.647 ± 0.093-0.718 ± 0.093-0.988 ± 0.095
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.3258 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.088 · 95% CI -0.088 to 0.265
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.3483 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.084 · 95% CI -0.092 to 0.261
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.8055 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.022 · 95% CI -0.156 to 0.201
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.3627 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.103 · 95% CI -0.119 to 0.326
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4404 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.087 · 95% CI -0.135 to 0.310
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.9939 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.001 · 95% CI -0.224 to 0.226
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.2716 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.128 · 95% CI -0.356 to 0.100
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.3175 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.116 · 95% CI -0.345 to 0.112
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0325 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.252 · 95% CI -0.483 to -0.021
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.1769 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.169 · 95% CI -0.415 to 0.077
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1343 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.188 · 95% CI -0.434 to 0.058
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0203 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.295 · 95% CI -0.544 to -0.046
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.2543 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.152 · 95% CI -0.415 to 0.110
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.2892 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.142 · 95% CI -0.405 to 0.121
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0243 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.306 · 95% CI -0.571 to -0.040
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6471 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.059 · 95% CI -0.312 to 0.194
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4123 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.106 · 95% CI -0.359 to 0.148
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0338 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.278 · 95% CI -0.534 to -0.021
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4841 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.095 · 95% CI -0.362 to 0.172
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.2627 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.152 · 95% CI -0.419 to 0.115
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0241 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.311 · 95% CI -0.581 to -0.041
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4881 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.093 · 95% CI -0.355 to 0.170
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.2205 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.164 · 95% CI -0.427 to 0.099
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0015 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.433 · 95% CI -0.699 to -0.168
SecondaryChange From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency'

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.

Time frame:
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
Reported as:
Least squares mean · units on a scale
Change From Baseline Over Time in the mRESQ-eD Item 'Burping Frequency'
units on a scalePlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Week 1-0.459 ± 0.071-0.416 ± 0.070-0.309 ± 0.070-0.416 ± 0.071
Week 2-0.669 ± 0.083-0.649 ± 0.082-0.556 ± 0.082-0.614 ± 0.084
Week 3-0.605 ± 0.085-0.705 ± 0.084-0.734 ± 0.084-0.754 ± 0.086
Week 4-0.701 ± 0.092-0.794 ± 0.091-0.797 ± 0.090-0.866 ± 0.093
Week 5-0.744 ± 0.091-0.832 ± 0.090-0.813 ± 0.090-0.910 ± 0.092
Week 6-0.801 ± 0.094-0.845 ± 0.093-0.845 ± 0.093-0.942 ± 0.095
Week 7-0.810 ± 0.099-0.896 ± 0.098-0.803 ± 0.097-0.909 ± 0.100
Week 8-0.809 ± 0.102-0.973 ± 0.101-0.920 ± 0.100-1.008 ± 0.103
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.6653 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.043 · 95% CI -0.152 to 0.238
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.1327 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.150 · 95% CI -0.046 to 0.345
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.6697 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.043 · 95% CI -0.155 to 0.241
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.8598 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.021 · 95% CI -0.210 to 0.251
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.3354 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.113 · 95% CI -0.118 to 0.344
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.6429 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.055 · 95% CI -0.179 to 0.289
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4010 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.101 · 95% CI -0.336 to 0.135
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.2821 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.129 · 95% CI -0.364 to 0.106
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.2189 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.149 · 95% CI -0.388 to 0.089
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4717 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.093 · 95% CI -0.346 to 0.161
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4572 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.096 · 95% CI -0.349 to 0.158
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.2064 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.165 · 95% CI -0.422 to 0.092
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.4932 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.088 · 95% CI -0.339 to 0.164
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.5897 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.069 · 95% CI -0.321 to 0.183
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.2014 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.166 · 95% CI -0.421 to 0.089
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7384 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.044 · 95% CI -0.304 to 0.215
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.7423 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.043 · 95% CI -0.303 to 0.216
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.2923 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.141 · 95% CI -0.404 to 0.122
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.5388 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.085 · 95% CI -0.359 to 0.188
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.9565 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.008 · 95% CI -0.266 to 0.281
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.4848 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.099 · 95% CI -0.376 to 0.179
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.2523 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.164 · 95% CI -0.445 to 0.117
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.4356 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.112 · 95% CI -0.393 to 0.170
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.1706 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.199 · 95% CI -0.485 to 0.086
SecondaryChange From Baseline in the Proportion of Heartburn-Free Days During 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.

Time frame:
Week 8
Reported as:
Least squares mean · proportion of days
Change From Baseline in the Proportion of Heartburn-Free Days During Week 8
proportion of daysPlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Change From Baseline in the Proportion of Heartburn-Free Days During Week 80.276 ± 0.0490.256 ± 0.0470.310 ± 0.0490.347 ± 0.049
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.7689 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.020 · 95% CI -0.155 to 0.115
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.6287 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.034 · 95% CI -0.103 to 0.170
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.3106 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.070 · 95% CI -0.066 to 0.207
SecondaryChange From Baseline in the Proportion of Heartburn-Free Days During 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.

Time frame:
Week 4
Reported as:
Least squares mean · proportion of days
Change From Baseline in the Proportion of Heartburn-Free Days During Week 4
proportion of daysPlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Change From Baseline in the Proportion of Heartburn-Free Days During Week 40.141 ± 0.0370.142 ± 0.0350.134 ± 0.0360.241 ± 0.036
Statistical analysis
  • Placebo BID vs 500 mg IW-3718 BID · ANCOVA · p = 0.9961 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.000 · 95% CI -0.100 to 0.101
  • Placebo BID vs 1000 mg IW-3718 BID · ANCOVA · p = 0.8829 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: -0.008 · 95% CI -0.109 to 0.094
  • Placebo BID vs 1500 mg IW-3718 BID · ANCOVA · p = 0.0527 (P-values are based on a pairwise comparison versus placebo in an ANCOVA model with fixed effect terms for treatment group and esophagitis stratum and baseline value as covariate.) · Ls mean difference: 0.100 · 95% CI -0.001 to 0.201

Adverse events

Collected over From the first dose of study drug through Week 8/End-of-treatment (Day 57 + 3 days) plus 7 days.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo BID0/70 (0%)2/70 (2.9%)16/70 (22.9%)
500 mg IW-3718 BID0/71 (0%)1/71 (1.4%)17/71 (23.9%)
1000 mg IW-3718 BID0/71 (0%)1/71 (1.4%)19/71 (26.8%)
1500 mg IW-3718 BID0/68 (0%)2/68 (2.9%)12/68 (17.6%)
Most frequent serious events
Most frequent serious events
EventPlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
Acute myocardial infarctionCardiac disorders0/700/710/711/68
Abortion spontaneousPregnancy, puerperium and perinatal conditions0/700/710/711/68
Non-cardiac chest painGeneral disorders1/700/710/710/68
SyncopeNervous system disorders1/700/710/710/68
Chest painGeneral disorders0/700/711/710/68
Selective abortionSurgical and medical procedures0/701/710/710/68
Most frequent other events
Most frequent other events
EventPlacebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BID
FlatulenceGastrointestinal disorders3/707/714/711/68
NauseaGastrointestinal disorders2/703/714/716/68
ConstipationGastrointestinal disorders5/706/716/715/68
DiarrhoeaGastrointestinal disorders5/702/713/713/68
InsomniaPsychiatric disorders5/700/711/710/68
Abdominal distensionGastrointestinal disorders4/702/714/712/68

Baseline characteristics

modified Intent-to-Treat Population: all randomized participants who received at least one dose of study treatment.

Age, Continuous
Age, Continuous(years)Placebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BIDTotal
Mean49.5 ± 12.951.4 ± 13.350.1 ± 11.249.4 ± 12.350.1 ± 12.4
Sex: Female, Male
Sex: Female, Male(Participants)Placebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BIDTotal
Female43464339171
Male27252829109
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Placebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BIDTotal
Hispanic or Latino923151764
Not Hispanic or Latino61485651216
Unknown or Not Reported00000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Placebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BIDTotal
Asian20013
Black or African American12891039
Caucasian54626254232
Other, Not Specified21036
Weekly Heartburn Severity Score (WHSS)
Weekly Heartburn Severity Score (WHSS)(score on a scale)Placebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BIDTotal
Mean3.18 ± 0.643.19 ± 0.723.12 ± 0.643.19 ± 0.713.17 ± 0.68
Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity'
Modified Reflux Symptom Questionnaire - Electronic Diary (mRESQ-eD) Item 'Heartburn Severity'(units on a scale)Placebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BIDTotal
Mean3.08 ± 0.633.01 ± 0.663.00 ± 0.643.08 ± 0.663.04 ± 0.65
mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity'
mRESQ-eD Item 'Burning Feeling Behind Breastbone or Center of Upper Stomach Severity'(units on a scale)Placebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BIDTotal
Mean2.85 ± 0.822.91 ± 0.822.77 ± 0.822.98 ± 0.782.88 ± 0.81
mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity'
mRESQ-eD Item 'Pain Behind Breastbone or Center of Upper Stomach Severity'(units on a scale)Placebo BID500 mg IW-3718 BID1000 mg IW-3718 BID1500 mg IW-3718 BIDTotal
Mean2.73 ± 0.872.80 ± 0.892.57 ± 0.952.85 ± 0.912.74 ± 0.91

7 further baseline measures are reported on the registry.

08

Study locations

62 sites
  • IW-3718 Investigator
    Dothan, Alabama 36305, United States
  • IW-3718 Investigator
    Phoenix, Arizona 85018, United States
  • IW-3718 Investigator
    Tucson, Arizona 85710, United States
  • IW-3718 Investigator
    Tucson, Arizona 85712, United States
  • IW-3718 Investigator
    Tucson, Arizona 85741, United States
  • IW-3718 Investigator
    North Little Rock, Arkansas 72117, United States
  • IW-3718 Investigator
    Anaheim, California 92801, United States
  • IW-3718 Investigator
    Carmichael, California 95608, United States
  • IW-3718 Investigator
    Chula Vista, California 91910, United States
  • IW-3718 Investigator
    La Mirada, California 90638, United States
  • IW-3718 Investigator
    Mission Hills, California 91345, United States
  • IW-3718 Investigator
    Newport Beach, California 92660, United States
  • IW-3718 Investigator
    Oakland, California 94612, United States
  • IW-3718 Investigator
    Sacramento, California 95821, United States
  • IW-3718 Investigator
    San Diego, California 92123, United States
  • IW-3718 Investigator
    Bristol, Connecticut 06010, United States
  • IW-3718 Investigator
    Waterbury, Connecticut 06708, United States
  • IW-3718 Investigator
    DeLand, Florida 32720, United States
  • IW-3718 Investigator
    Hollywood, Florida 33024, United States
  • IW-3718 Investigator
    Inverness, Florida 34452, United States
  • IW-3718 Investigator
    Jupiter, Florida 33458, United States
  • IW-3718 Investigator
    Lauderdale Lakes, Florida 33319, United States
  • IW-3718 Investigator
    Miami Lakes, Florida 33014, United States
  • IW-3718 Investigator
    Miami, Florida 33126, United States
  • IW-3718 Investigator
    Miami, Florida 33135, United States
  • IW-3718 Investigator
    Port Orange, Florida 32129, United States
  • IW-3718 Investigator
    Clive, Iowa 50325, United States
  • IW-3718 Investigator
    Bowling Green, Kentucky 42101, United States
  • IW-3718 Investigator
    Monroe, Louisiana 71201, United States
  • IW-3718 Investigator
    Annapolis, Maryland 21401, United States
  • IW-3718 Investigator
    Baltimore, Maryland 21215, United States
  • IW-3718 Investigator
    Chevy Chase, Maryland 20815, United States
  • IW-3718 Investigator
    Chesterfield, Michigan 48047, United States
  • IW-3718 Investigator
    Wyoming, Michigan 49519, United States
  • IW-3718 Investigator
    Las Vegas, Nevada 89128, United States
  • IW-3718 Investigator
    Reno, Nevada 89511, United States
  • IW-3718 Investigator
    Egg Harbor Township, New Jersey 08234, United States
  • IW-3718 Investigator
    Great Neck, New York 11021, United States
  • IW-3718 Investigator
    Great Neck, New York 11023, United States
  • IW-3718 Investigator
    Kew Gardens, New York 11415, United States
  • IW-3718 Investigator
    New York, New York 10065, United States
  • IW-3718 Investigator
    Asheville, North Carolina 28801, United States
  • IW-3718 Investigator
    Raleigh, North Carolina 27612, United States
  • IW-3718 Investigator
    Fargo, North Dakota 58103, United States
  • IW-3718 Investigator
    Cleveland, Ohio 44109, United States
  • IW-3718 Investigator
    Columbus, Ohio 43213, United States
  • IW-3718 Investigator
    Lima, Ohio 45806, United States
  • IW-3718 Investigator
    Norman, Oklahoma 73071, United States
  • IW-3718 Investigator
    Oklahoma City, Oklahoma 73104, United States
  • IW-3718 Investigator
    Pittsburgh, Pennsylvania 15243, United States
  • IW-3718 Investigator
    Charleston, South Carolina 29412, United States
  • IW-3718 Investigator
    Chattanooga, Tennessee 37421, United States
  • IW-3718 Investigator
    Germantown, Tennessee 38138, United States
  • IW-3718 Investigator
    Nashville, Tennessee 37232, United States
  • IW-3718 Investigator
    El Paso, Texas 79905, United States
  • IW-3718 Investigator
    Houston, Texas 77098, United States
  • IW-3718 Investigator
    San Antonio, Texas 78209, United States
  • IW-3718 Investigator
    San Antonio, Texas 78229, United States
  • IW-3718 Investigator
    Sandy, Utah 84092, United States
  • IW-3718 Investigator
    South Ogden, Utah 84405, United States
  • IW-3718 Investigator
    Christiansburg, Virginia 24073, United States
  • IW-3718 Investigator
    Lynchburg, Virginia 24502, United States
09

References and documents

Publications

  • 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. PubMed 32092310 ↗
  • 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. PubMed 31977454 ↗

Study documents

  • Statistical analysis plan · Jun 15, 2017
  • Study protocol · Jul 27, 2016

Documents are hosted by the registry — open the source record to download them.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Oct 15, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02637557
Lead sponsor
Ironwood Pharmaceuticals, Inc.
Responsible party
Sponsor
First posted
Dec 22, 2015
Start date
Mar 1, 2016
Primary completion
Apr 26, 2017
Completion
Apr 26, 2017
Results posted
Oct 15, 2019
Last update
Oct 15, 2019

Study contacts

Lara Lane
study director · Ironwood Pharmaceuticals, Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2019. You cannot join it, but the record below documents what was studied.

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